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OP0311 Incidence of Severe Knee and Hip Osteoarthritis in Relation to the Metabolic Syndrome and its Components: A Prospective Cohort Study
... Obesity is a known modifiable risk factor for knee OA [12]. Studies suggest that obesity increases the risk of OA not only by the mechanical load on weight-bearing joints but also through metabolic mechanisms [12,13]. ...
... Similarly, Sower et al. found that obese women with cardiometabolic clustering were more likely to report persistent knee pain and impaired physical functioning [38]. Researchers have suggested that people with MetS accompanied by systemic inflammation may experience increased pain for the same severity of structural OA [13,39,40]. In another study, women with greater MetS severity at the baseline demonstrated the progression of osteophytes, bone marrow lesions (BMLs), and cartilage defects, suggesting an increased level of structural knee OA progression over a five-year follow-up [41]. ...
... A few other studies found MetS to be associated with knee pain; however, the association disappeared after adjustment for BMI [35,40,42]. However, in line with our findings, Hussain et al. found that accumulation of MetS components was associated with an increased risk of severe knee OA, independent of BMI [13]. ...
Abstract
Objective
Metabolic syndrome (MetS) is characterised by the clustering of central obesity with metabolic abnormalities. We aimed to describe the association of MetS and trajectories of MetS over 10–13 years with knee symptoms in general population-based middle-aged adults.
Methods
Fasting blood biochemistry, waist circumference and blood pressure measures were collected during Childhood Determinants of Adult Health (CDAH)-1 study (year:2004–6; n = 2447; mean age:31.48 ± 2.60) and after 10–13 year at CDAH-3 (year:2014–2019; n = 1549; mean age:44 ± 2.90). Participants were defined as having MetS as per International Diabetes Federation (IDF) definition. Knee symptoms were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale at CDAH-3 (mid-adulthood).
Results
The prevalence of MetS increased from 8 % at young adulthood (female:52.06 %) to 13 % in mid-adulthood (female:53.78 %) over 10–13 years. Presence of MetS at mid-adulthood was associated with knee symptoms at mid-adulthood [ratio of means (RoM): 1.33; 95%CI:1.27,1.39]. Four MetS trajectories were identified—‘No MetS’ (85.01 %); ‘Improved MetS’ (2.14 %), ‘Incident MetS’ (8.81 %), and ‘Persistent MetS, (4.04 %). Compared to ‘No MetS‘, ‘Persistent MetS’ [RoM:1.15; 95%CI:1.06,1.25], ‘Incident MetS’ [RoM:1.56; 95%CI:1.48,1.65], and ‘Improved MetS’ [RoM:1.22; 95%CI:1.05,1.41] was associated with higher knee symptoms. Notably, ‘Incident MetS’ was strongly associated with knee symptoms [RoM: 1.56; 95%CI:1.48,1.65] and pain [RoM:1.52; 95%CI:1.37,1.70] at mid-adulthood.
Conclusion
In this sample of middle-aged adults, there was a significant positive association between MetS and knee symptoms. Relative to those without MetS at either life stage, the elevation in mean knee pain scores was more pronounced for those who developed MetS after young adulthood than for those who had MetS in young adulthood.
... To this end, several studies have demonstrated an association between MetS and knee OA (15)(16)(17). However, the only two studies of MetS and hip OA (18,19) used total hip replacement status as a proxy for severe OA, and neither showed a significant association with MetS. Because obesity and medical comorbidities including those that comprise MetS may be considered relative contraindications for elective total hip replacement, joint replacement status may underestimate the overall prevalence of OA and selectively underestimate both MetS and obesity among individuals with total joint replacement. ...
... Although some studies have shown an association between knee OA and MetS (39), ours is the first to suggest a significant association of MetS with hip OA in women. This novel finding may be underscored by the fact that clinical hip OA, rather than total hip replacement status, was assessed in our study (18,19). Some previous studies used total hip arthroplasty status alone as a surrogate for OA, which likely underestimates the prevalence of OA, particularly for women (21), providing a plausible explanation for the disparate results. ...
... We performed secondary analyses using only the radiographic OA definition, and these yielded the same results but with smaller or nonsignificant effect sizes, which is consistent with the idea that the clinical hip OA definition identifies a more homogenous group of individuals with more severe hip OA. Additionally, previous studies of hip OA and MetS have used total hip replacement status as a surrogate measure (18,19), which may have underestimated the outcome prevalence because not all patients who have hip OA elect to undergo arthroplasty. ...
Objective:
Metabolic dysregulation frequently co-occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA.
Methods:
In two parallel cross-sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2 ) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics.
Results:
Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37-15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39-3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men.
Conclusion:
In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.
... For the remaining 34 potential relevant studies that underwent full text review, 29 were further excluded based on reasons listed in Fig 1. Finally, five prospective cohort studies were included in the meta-analysis [23][24][25][26][27]. The three studies identified by manual search were not finally included in the meta-analysis because they were not relevant to the aim of the meta-analysis [28,29], or not a prospective cohort study [30]. ...
... The characteristics of the included studies are summarized in Table 1. Overall, five prospective cohort studies with 94,965 community-derived participants were included in the meta-analysis [23][24][25][26][27]. These studies were published between 2009 and 2019, and performed in Sweden, Austria, the Unites States, Norway, and Finland, respectively. ...
... The mean ages of the included participants varied from 49 to 65 years, and the proportions of male ranged from 40% to50%. As for the diagnostic criteria for MetS, all of the included used the adult treatment panel IIInational cholesterol education program (ATPIII-NCEP) criteria except for one study [23,[25][26][27], in which the International Diabetes Federation (IDF) criteria was used [24]. According to the ATPIII-NECP criteria, subjects were considered to have MetS if they met at least 3 of the following 5 criteria: 1) abdominal obesity (waist circumference � 102 cm in men and � 88 cm ...
Background
Cross-sectional studies suggest an association between metabolic syndrome (MetS) and knee osteoarthritis (KOA). We performed a meta-analysis to evaluate whether MetS is an independent risk factor for KOA.
Methods
Prospective cohort studies evaluating the association between MetS and KOA in general population were retrieved from PubMed and Embase. Only studies with multivariate analyses were included. Data were pooled with a random-effect model, which is considered to incorporate heterogeneity among the included studies.
Results
Five studies including 94,965 participants were included, with 18,990 people with MetS (20.0%). With a mean follow-up duration of 14.5 years, 2,447 KOA cases occurred. Pooled results showed that MetS was not significant associated with an increased risk of KOA after controlling of factors including body mass index (adjusted risk ratio [RR]: 1.06, 95% CI: 0.92~1.23, p = 0.40; I ² = 33%). Subgroup analysis showed that MetS was independently associated with an increased risk of severe KOA that needed total knee arthroplasty (RR = 1.16, 95% CI: 1.03~1.30, p = 0.02), but not total symptomatic KOA (RR = 0.84, 95% CI: 0.65~1.08, p = 0.18). Stratified analyses suggested that MetS was independently associated with an increased risk of KOA in women (RR = 1.23, 95% CI: 1.03~1.47, p = 0.02), but not in men (RR = 0.90, 95% CI: 0.70~1.14, p = 0.37).
Conclusions
Current evidence from prospective cohort studies did not support MetS was an independent risk factor of overall KOA in general population. However, MetS may be associated with an increased risk of severe KOA in general population, or overall KOA risk in women.
... However, these results are not consistent. Some studies indicated that MetS is significantly associated with an increased incidence of OA [10][11][12], whereas many others demonstrated that the incidence of OA is not higher in MetS [13]. A meta-analysis between MetS and OA in 2016 showed that MetS is positively associated with OA of the knee [14]. ...
... The characteristics of these eleven studies are shown in Table 1. Of these studies, eight identified MetS by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria [12,13,[16][17][18][19][37][38][39], one by the International Diabetes Federation (IDF) criteria [11], one by AHA/NHLBI MetS criteria [18] and one by the Japan MetS criteria [10]. OA was identified by X-ray in nine studies [10, 12, 13, 16-19, 37, 39] and knee replacement in two [11,38]. ...
... Of these studies, eight identified MetS by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria [12,13,[16][17][18][19][37][38][39], one by the International Diabetes Federation (IDF) criteria [11], one by AHA/NHLBI MetS criteria [18] and one by the Japan MetS criteria [10]. OA was identified by X-ray in nine studies [10, 12, 13, 16-19, 37, 39] and knee replacement in two [11,38]. All included studies enrolled participants aged over 50 [10-13, 16-19, 37-39]. ...
Background:
Emerging observational studies suggest an association between metabolic syndrome (MetS) and osteoarthritis (OA). This meta-analysis was conducted to examine whether or not there is a bidirectional relationship between MetS and OA.
Methods:
The PubMed and Embase databases were searched from their inception to October 2019. We selected studies according to predefined criteria. Random effects were selected to calculate two sets of pooled risk estimates: MetS predicting OA and OA predicting MetS.
Results:
A total of seven cross-sectional studies and four cohort studies met the criteria for MetS predicting the onset of OA. Another six cross-sectional studies and one cohort study met the criteria for OA predicting the onset of MetS. The pooled odds risk (OR) for OA incidences associated with baseline MetS was 1.45 (95% CI 1.27-1.66). The OR for MetS incidences associated with baseline OA was 1.90 (95% CI 1.11-3.27). In an overall analysis, we found that MetS was associated with prevalent OA in both cross-sectional studies (OR = 1.32, 95% CI 1.21-1.44) and cohort studies (OR = 1.76, 95% CI 1.29-2.42). No indication of heterogeneity was found in the cross-sectional studies (p = 0.395, I2 = 4.8%), whereas substantial heterogeneity was detected in the cohort studies (p = 0.000, I2 = 79.3%).
Conclusion:
Meta-analysis indicated a bidirectional association between MetS and OA. We advise that patients with MetS should monitor their OA status early and carefully, and vice versa.
... Eventually, after evaluation of the full texts, eight studies were excluded for the reason that they did not satisfy our inclusion criteria: three studies offered inadequate information [25][26][27], three studies did not offer ORs or RRs for OA or adequate information to calculate these variables [28][29][30], and two studies were removed that either did not have dyslipidemia as an exposure or did not have OA as an outcome [31,32]. Ultimately, nine available observational articles were recognized for our meta-analysis [33][34][35][36][37][38][39][40][41]. Table 1 presents the principal features of the studies included in the meta-analysis, all of which were observational studies. ...
... Reports from four studies permitted the calculation of effect estimates for OA [34][35][36]38]. All of the cohort studies were population based, and the follow-up Full text articles assessed for eligibility (n = 17) ...
... Seven studies reported data on knee or hip osteoarthritis, but not all of the studies were adjusted for BMI or physical activity. Zhou et al. [39], Xie et al. [37], Engstrom et al. [35], Han et al. [36], and Monira Hussain et al. [34] reported on knee or hip osteoarthritis adjusted for physical activity (activity level). Hussain et al. [34] reported on knee osteoarthritis adjusted for BMI. ...
Background. According to several studies, the autoimmune response may lead to osteoarthritis and dyslipidemia and may affect the homeostasis of the human body’s internal environment and then cause its own immune regulation. Consequently, the risk of osteoarthritis might be increased by dyslipidemia, but this association is not universally acknowledged. Therefore, a systematic review and meta-analysis was conducted to study the relationship between dyslipidemia and the risk of osteoarthritis. Methods. In this study, PubMed, EMBASE, and the ISI Web of Science were used to identify related studies published before July 2018. The relationship between dyslipidemia and the risk of osteoarthritis was evaluated on the basis of relative risk (RR) values and the corresponding 95% confidence intervals (CIs). To further investigate this relationship, we also employed the random effects model proposed by DerSimonian and Laird. Results. A total of nine studies were included to study the effect of dyslipidemia on the risk of osteoarthritis, including four cohort, three case-control, and two cross-sectional studies. Among these studies, six stated data for knee osteoarthritis, two reported on hand osteoarthritis, and one reported on hip osteoarthritis. A total of 53,955 participants were included in the meta-analysis, comprising 22,501 patients with OA (19,733 hand OA, 2,679 knee OA, and 89 hip OA). Based on the meta-analysis of case-control and cross-sectional studies, osteoarthritis was clearly higher in those with dyslipidemia compared to those who did not suffer from dyslipidemia (case-control: ; –1.46; cross-sectional: ; -1.46). In addition, the meta-analysis of cohort studies did not present any relationship between dyslipidemia and OA (; –1.14). Conclusions. Even though our meta-analysis of case-control and cross-sectional studies suggested a strong relationship between dyslipidemia and osteoarthritis; this relationship was not validated by our meta-analysis of only cohort studies. As a result, further investigation needs to be conducted on the relationship between dyslipidemia and osteoarthritis, considering the significant public health relevance of the topic.
1. Introduction
Osteoarthritis (OA) refers to a chronic degenerative disease that involves the cartilage, as well as its surrounding tissues [1]. OA is considered the most common joint disease, and nearly 10-12% of the population suffers from OA [2]. In addition, it is expected that this number will increase dramatically due to the quickly increasing aging population combined with the growing prevalence of obesity [3]. Consequently, osteoarthritis is considered to have a negative influence on the health economy [4]. It can be forecast that by the year 2032, an additional 26,000 per million patients over the age of 45 will present to their general practitioner with osteoarthritis compared to 2012 [5]. OA is associated with age, female gender, obesity, joint injury, and career, as well as a high level of physical activity [5]. In addition, the autoimmune response of the synovium plays an important role in rheumatoid arthritis. In recent years, the immunological pathogenesis of synovium in osteoarthritis has attracted the attention of many researchers. Whether the immune mechanism and inflammatory mediators are involved in the occurrence and development of osteoarthritis deserves further discussion. This may provide a new research idea for the pathogenesis of osteoarthritis, to improve our understanding of the development of this disease and change the way of treatment. In recent years, research has shown that metabolic syndrome is closely associated with OA, which is even a part of generalized metabolic disorder. Metabolic syndrome is composed of a bundle of interrelated metabolic risk factors, including diabetes, obesity, dyslipoproteinemia, and hypertension [6]. Furthermore, the incidence of metabolic syndrome is very high; it has been estimated to be as high as 26.7% in industrialized countries [6]. In the context of musculoskeletal disorders, metabolic syndrome has increasingly gained more attention because of its relationship with knee OA [7]. Obesity, the main feature in metabolic syndrome, is overwhelmingly related to degenerative joint changes in regard to mechanical load [8]. Alternatively, obesity-related OA can afflict nonweight-bearing joints (e.g., the hands), signifying a role of adipokines (circulating mediators released by adipose tissue), such as leptin. Thus, OA may have a systemic metabolic element [9]. In addition, OA can be categorized into three phenotypes: metabolic OA, age-related OA, and injury-related OA [10]. Nevertheless, as one of the components of metabolic syndrome, the role of dyslipidemia in the pathogenesis of OA is not completely understood. Dyslipidemia may affect the homeostasis of the human body’s internal environment and then cause its own immune regulation. Dyslipidemia is related to chronic low-grade inflammation and oxidative stress, likely increasing the development of OA [11, 12]. A survey carried out by Ghandehari concluded that approximately 51.4 million US adults presented with high cholesterol and triglycerides, in addition to 36.1 million with elevated low-density lipoproteins [13]. As a result, we chose to conduct a systematic review and meta-analysis of the published observational studies to better comprehend the relationship between dyslipidemia and the risk of OA.
2. Materials and Methods
This research was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [14] and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines [15].
2.1. Data Sources and Search Strategy
Published studies in PubMed, EMBASE, and the Web of Science were searched based on the following keywords: (“hyperlipidaemia” OR “dyslipidemia” OR “triglyceride” OR “cholesterol” OR “lipoprotein” OR “lipid” OR “metabolic syndrome”) and (“OA”). No restrictions on language or the date of publication were placed. Additionally, this study also searched the reference lists. Unpublished studies and original data were not included.
2.2. Eligibility Criteria for Study Selection
The eligibility criteria were as follows: study design (randomized controlled trials and cohort, case-control, or cross-sectional studies); an exposure factor of blood lipid levels and an outcome of OA; availability of the odds ratio (OR)/risk ratio (RR) values and corresponding 95% confidence intervals (CIs) for dyslipidemia patients and the general population; or the availability of sufficient information to measure these variables. The most recent all-inclusive study was searched under the condition that two studies used the same population. The definition of dyslipidemia was in line with the US National Cholesterol Education Program Adult Treatment Panel III guidelines. In accordance with the National Cholesterol Education Program, the definition of dyslipidemia was high-density lipoprotein cholesterol , as well as total cholesterol, low-density lipoprotein cholesterol (LDL-C), and TG levels of ≥200, ≥130, and ≥130 mg/dL, respectively [5]. The definition of osteoarthritis was in line with the American College of Rheumatology (ACR) clinical and clinical plus radiographic criteria [6]. The ACR classification criteria for (OA) permits the categorization of individuals for hand, knee, and hip OA [6]. We strictly abided by this classification standard.
2.3. Data Abstraction and Quality Assessment
Two scholars (J.X. and J.L.) obtained the essential information from the chosen studies according to the standard. The following information was gathered: name of the first author, publication year, country in which the research was carried out, study design, number of participants, period of follow-up, sources of controls, potential adjusted confounding variables, OR/RR values, and 95% CIs.
To date, no available common scale has been proposed to evaluate the quality of all kinds of observational studies. As a result, two authors individually employ the modified Newcastle-Ottawa Scale (NOS) [16] as reported by Zhu et al. [17] to assess the quality of the included studies. Quality types were allocated in accordance with the scores of each study, consisting of high quality (score 7-9), medium quality (score 4-6), and low quality (score less than 4) [18]. The maximum total score could reach 9 points, and discrepancies were solved by mutual agreement.
2.4. Statistical Analysis
The random effects model put forward by DerSimonian and Laird was applied to investigate the relationship between dyslipidemia and the risk of OA among the cohort studies [19]. The statistic was employed to evaluate heterogeneity between the studies. Low, medium, and high heterogeneities were categorized as 25%, 50%, and 75%, respectively [20]. Definite heterogeneity was assumed if the value was less than 0.1. Sensitivity analyses were conducted by altering the pooling model [21]. In addition, a sensitivity analysis was carried out to evaluate the influence of each individual study on the summarized estimate by means of successively excluding one research study at a time. Publication bias was assessed using Begg’s [22] and Egger’s [23] tests. No testing for funnel plot asymmetry was carried out due to the limited number of studies included in the analysis () [24].
Furthermore, we conducted a meta-analysis of the case-control and cross-sectional studies in regard to the influence of dyslipidemia on the risk of OA and expressed the results as pooled risk ratios with 95% CIs with the application of a random effects model.
STATA version 12.0 (Stata) was carried out to perform all statistical analyses.
3. Results
3.1. Study Selection and Study Characteristics
The process of study selection for the meta-analysis can be found in Figure 1. In total, 1,917 articles were obtained through the initial search, and 502 were duplicates. An additional 1,266 studies were removed based on the title and abstract. Eventually, after evaluation of the full texts, eight studies were excluded for the reason that they did not satisfy our inclusion criteria: three studies offered inadequate information [25–27], three studies did not offer ORs or RRs for OA or adequate information to calculate these variables [28–30], and two studies were removed that either did not have dyslipidemia as an exposure or did not have OA as an outcome [31, 32]. Ultimately, nine available observational articles were recognized for our meta-analysis [33–41].
... Hip OA (HOA) is a common chronic condition, which will affect a quarter of the population by age 85 [5]. The evidence that OA is associated with CVD, DM, or features of the metabolic syndrome (e.g., hyperglycemia, insulin resistance, obesity, and dyslipidemia) is mixed and is overall stronger for knee OA compared with HOA [6]. The evidence of a specific association between HOA and CVD remains undecided [7], with few studies focused on DM. ...
... Higher BMI has been associated with greater selfreported pain and poorer function among individuals awaiting hip replacement surgery, despite similar radiographic severity of disease [12]. Some studies have reported no association between the metabolic syndrome or its individual components in severe HOA [6]. However, one or more comorbid conditions conferred a higher risk of revision of hip arthroplasty (HR 1.16, 95% CI [1.08, 1.23]) in a large Finnish registry; this was mostly attributable to CVD and particularly heart failure [4]. ...
... Carolina at Chapel Hill, Chapel Hill, USA. 6 ...
Background:
We examined the association of three common chronic conditions (obesity, diabetes mellitus [DM], and cardiovascular disease [CVD]) with transitions among states of hip osteoarthritis (HOA).
Methods:
This longitudinal analysis used data from the Johnston County Osteoarthritis Project (JoCo OA, n = 3857), a community-based study in North Carolina, USA, with 18.4 ± 1.5 years of follow-up. Transitions across the following states were modeled: development of radiographic HOA (rHOA; Kellgren-Lawrence grade [KLG] of< 2); development of hip symptoms (self-reported hip pain, aching, or stiffness on most days) or symptomatic HOA (sxHOA; rHOA and symptoms in the same hip), and resolution of symptoms. Obesity (body mass index ≥ 30 kg/m2) and self-reported DM and CVD were the time-dependent comorbid conditions of interest. Markov multi-state models were used to estimate adjusted hazard ratios and 95% confidence intervals to describe the associations between the conditions and HOA states.
Results:
The sample included 33% African Americans, 39% men, with a mean (SD) age of 62.2 (9.8) years; the frequencies of the comorbidities increased substantially over time. When considered individually, obesity was associated with incident hip symptoms, while CVD and DM were associated with reduced symptom resolution. For those with > 1 comorbidity, the likelihood of incident sxHOA increased, while that of symptom resolution significantly decreased. When stratified by sex, the association between obesity and incident symptoms was only seen in women; among men with DM versus men without, there was a significant (~ 75%) reduction in symptom resolution in those with rHOA. When stratified by race, African Americans with DM, versus those without, were much more likely to develop sxHOA.
Conclusions:
Comorbid chronic conditions are common in individuals with OA, and these conditions have a significant impact on the persistence and progression of HOA. OA management decisions, both pharmacologic and non-pharmacologic, should include considerations of the inter-relationships between OA and common comorbidities such as DM and CVD.
... The methods of previous studies have been diverse in terms of the covariates and endpoints they have included, and some studies have not adjusted for body mass index (BMI). [11][12][13][14][15][16][17][18][19][20] Many studies have found that having metabolic syndrome is associated with an increased likelihood of knee OA, but this connection has attenuated after adjustment for BMI. [11][12][13][14]21 The previous results concerning individual metabolic syndrome components and their predictive ability of knee OA are controversial. ...
... [11][12][13][14]21 The previous results concerning individual metabolic syndrome components and their predictive ability of knee OA are controversial. 5,[11][12][13][14][15][16][17][18][19][20] Given the conflicting results of previous studies, the objective of this study was to assess the association between metabolic syndrome and its individual components and incident clinical knee OA in a longitudinal setting over a 32-year follow-up period. ...
... Central obesity is strongly associated with BMI, a known risk factor for knee OA. 32,33 In several previous studies, [12][13][14][15]20,21,[34][35][36] central obesity has predicted an increased risk of knee OA or total knee replacement due to OA in adjusted analyses, but in most of these studies, this association attenuated after adjustment for BMI. In 2 of these studies, the association of waist circumference and knee OA persisted after adjustment for BMI. ...
Objectives
To examine whether metabolic syndrome or its individual components predict the risk of incident knee osteoarthritis (OA) in a prospective cohort study during a 32-year follow-up period.
Design
The cohort consisted of 6274 participants of the Mini-Finland Health Survey, who were free from knee OA and insulin-treated diabetes at baseline. Information on the baseline characteristics, including metabolic syndrome components, hypertension, elevated fasting glucose, elevated triglycerides, reduced high-density lipoprotein, and central obesity were collected during a health examination. We drew information on the incidence of clinical knee OA from the national Care Register for Health Care. Of the participants, 459 developed incident knee OA. In our full model, age, gender, body mass index, history of physical workload, smoking history, knee complaint, and previous injury of the knee were entered as potential confounding factors.
Results
Having metabolic syndrome at baseline was not associated with an increased risk of incident knee OA. In the full model, the hazard ratio for incident knee OA for those with metabolic syndrome was 0.76 (95% confidence interval [0.56, 1.01]). The number of metabolic syndrome components or any individual component did not predict an increased risk of knee OA. Of the components, elevated plasma fasting glucose was associated with a reduced risk of incident knee OA (hazard ratio 0.71, 95% confidence interval [0.55, 0.91]).
Conclusions
Our findings do not support the hypothesis that metabolic syndrome or its components increase the risk of incident knee OA. In fact, elevated fasting glucose levels seemed to predict a reduced risk.
... Although MetS has several specific definitions, it can be described as a combination of hypertension, dyslipidaemia, insulin resistance and abdominal obesity [17]. Individuals with OA have an increased prevalence of MetS [18] and individual components of MetS have also been associated with symptomatic OA in prospective studies in middle-age and elderly population [10,[19][20][21][22][23][24][25]. In addition, development of both OA and MetS has been associated not only with high BMI but also hormonal changes [8,21,26,27]. ...
... However, Monira Hussain et al. showed in a large prospective cohort study that MetS was associated with increased risk of severe knee OA (requiring knee replacement) independent of BMI. Furthermore, that study also showed no such relationship for severe hip OA [25]. ...
Background
Osteoarthritis (OA) is the most common form of arthritis with multiple risk factors implicated including female sex and obesity. Metabolic dysregulation associated with obesity leading to metabolic syndrome is a proposed component of that association. Polycystic ovary syndrome (PCOS) commonly affects women of reproductive age and these women are at higher risk of developing metabolic syndrome and thus likely to represent a high-risk group for early OA development. There are no published studies exploring the epidemiology of knee, hip and hand OA in women diagnosed with PCOS.
Study aim
To assess the prevalence and incidence of knee, hip and hand osteoarthritis (OA) in women with polycystic ovary syndrome (PCOS) when compared with age-matched controls.
Methods
Prospective Danish national registry-based cohort study. The prevalence of OA in 2015 and incidence rates of OA over 11.1 years were calculated and compared in more than 75,000 Danish women with either a documented diagnosis of PCOS ± hirsutism (during the period of 1995 to 2012) or age-matched females without those diagnoses randomly drawn from the same population register.
Results
In 2015, the prevalence of hospital treated knee, hip and hand OA was 5.2% in women with PCOS diagnosis. It was 73% higher than that seen in age-matched controls. Significantly higher incidence rates were observed in the PCOS cohort compared with the age-matched controls during the follow-up period (up to 20 years), with the following hazard ratios (HR): 1.9 (95% CI 1.7 to 2.1) for knee, 1.8 (95% CI 1.3–2.4) for hand and 1.3 (95% CI 1.1 to 1.6) for hip OA. After excluding women with obesity, similar associations were observed for knee and hand OA. However, risk of developing hip OA was no longer significant.
Conclusions
In this large prospective study, women with PCOS diagnosis had higher prevalence and accelerated onset of OA of both weight and non-weight bearing joints, when compared with age-matched controls. Further studies are needed to understand the relative effect of metabolic and hormonal changes linked with PCOS and their role in promoting development of OA.
... Although MetS has several speci c de nitions, it can be described as a combination of hypertension, dyslipidaemia, insulin resistance and abdominal obesity (17). Individuals with OA have an increased prevalence of MetS (18) and individual components of MetS have also been associated with symptomatic OA in prospective studies in middle-age and elderly population (10,(19)(20)(21)(22)(23)(24)(25). In addition, development of both OA and MetS has been associated not only with high BMI but also hormonal changes (21,(26)(27)(28). ...
... However, Monira Hussain et al. showed in a large prospective cohort study that MetS was associated with increased risk of severe knee OA (requiring knee replacement) independent of BMI. Furthermore, that study also showed no such relationship for severe hip OA (25). ...
Background. Osteoarthritis (OA) is the most common form of arthritis with multiple risk factors implicated including female sex and obesity. Metabolic dysregulation associated with obesity leading to Metabolic Syndrome is a proposed component of that association. Polycystic ovary syndrome (PCOS) commonly affects women of reproductive age and these women are at higher risk of developing Metabolic Syndrome and thus likely to represent a high-risk group for early OA development. There are no published studies exploring the epidemiology of knee, hip and hand OA in women diagnosed with PCOS.
Study aim. To assess the prevalence and incidence of knee, hip and hand osteoarthritis (OA) in women with Polycystic Ovary Syndrome (PCOS) when compared with age-matched controls.
Methods. Prospective Danish national registry-based cohort study. The prevalence of OA in 2015 and incidence rates of OA over 11.1 years were calculated and compared in more than 75,000 Danish women with either a documented diagnosis of PCOS and/or hirsutism (during the period of 1995 to 2012) or age-matched females without those diagnoses randomly drawn from the same population register.
Results. In 2015, the prevalence of hospital treated knee, hip and hand OA was 5.2% in women with PCOS diagnosis. It was 73% higher than that seen in age-matched controls. Significantly higher incidence rates were observed in the PCOS cohort compared with the age-matched controls during the follow-up period (up to 20 years), with the following hazard ratios (HR): 1.9 (95%CI: 1.7 to 2.1) for knee, 1.8 (95%CI: 1.3-2.4) for hand and 1.3 (95%CI: 1.1 to 1.6) for hip OA. After excluding women with obesity, similar associations were observed for knee and hand OA. However, risk of developing hip OA was no longer significant.
Conclusions. In this large prospective study, women with PCOS diagnosis had higher prevalence and accelerated onset of OA of both weight and non-weight bearing joints, when compared with age-matched controls. Further studies are needed to understand the relative effect of metabolic and hormonal changes linked with PCOS and their role in promoting development of OA.
... With an increase in body weight in the context of metabolic syndrome and an increase in fat tissue mass, there is an acceleration in the development of degenerative changes, especially in the joints of the hands and knees. Introducing an appropriate diet and increasing physical activity can slow down the degenerative process [22,23]. Epidemiological studies indicate that the degree of degenerative changes is associated with serum cholesterol levels. ...
Osteoarthritis (OA) ranks among the most prevalent inflammatory diseases affecting the musculoskeletal system and is a leading cause of disability globally, impacting approximately 250 million individuals. This study aimed to assess the relationship between the severity of knee osteoarthritis (KOA) and body composition in postmenopausal women using bioimpedance analysis (BIA). The study included 58 postmenopausal females who were candidates for total knee arthroplasty. The control group consisted of 25 postmenopausal individuals with no degenerative knee joint changes. The anthropometric analysis encompassed the body mass index (BMI), mid-arm and mid-thigh circumferences (MAC and MTC), and triceps skinfold thickness (TSF). Functional performance was evaluated using the 30 s sit-to-stand test. During the BIA test, electrical parameters such as membrane potential, electrical resistance, capacitive reactance, impedance, and phase angle were measured. Additionally, body composition parameters, including Total Body Water (TBW), Extracellular Water (ECW), Intracellular Water (ICW), Body Cellular Mass (BCM), Extracellular Mass (ECM), Fat-Free Mass (FFM), and Fat Mass (FM), were examined. The study did not find any statistically significant differences in the electrical parameters between the control (0–1 grade on the K–L scale) and study groups (3–4 grade on the K–L scale). However, statistically significant differences were observed in BMI, fat mass (FM), arm circumference, triceps skinfold thickness, and sit-to-stand test results between the analyzed groups. In conclusion, the association between overweight and obesity with KOA in postmenopausal women appears to be primarily related to the level of adipose tissue and its metabolic activity.
... About one fifth of the individuals without RKOA fulfilled the IDF criteria for MetS which is a percentage that is comparable to the general population (22-28%) [37]. One third of those with RKOA fulfilled the criteria for MetS, which is fewer than reported by other studies (43-59%) [7,38]. An explanation for this disparity between the data in the present study and other studies could be the use of different criteria for MetS. ...
Objective
Metabolic factors have been shown to be associated to severe radiographic knee osteoarthritis (RKOA). However, more knowledge is needed in early clinical knee osteoarthritis (KOA). The aim was to study associations between metabolic factors and radiographic knee osteoarthritis (OA) in individuals with knee pain. A second aim was to study associations between metabolic factors and RKOA in those with normal BMI and in those overweight/obese, respectively.
Method
This cross-sectional study included 282 individuals with knee pain (without cruciate ligament injury) and aged 30–67 years, and 70% women. Waist circumference, body mass index (BMI), proportion of fat and visceral fat area (VFA) were assessed. RKOA was defined as Ahlbäck grade 1 in at least one knee. Fasting blood samples were taken and triglycerides, cholesterol (total, low density lipoprotein (LDL) and high density lipoprotein (HDL)), C-reactive protein (CRP), glucose, HbA1C were analysed. Metabolic syndrome was defined in accordance with the International Diabetes Federation (IDF). Associations were analysed by logistic regression.
Results
Individuals with RKOA were older, had higher BMI, higher VFA, larger waist circumference and had increased total cholesterol, triglycerides and LDL-cholesterol, but not fasting glucose. There was no difference between the group with RKOA vs. non-radiographic group regarding the presence of metabolic syndrome. In a subgroup analysis of individuals with normal BMI (n = 126), those with RKOA had higher VFA, more central obesity, higher levels of CRP and total cholesterol, compared with individuals without RKOA. In individuals with obesity, age was the only outcome associated to RKOA.
Conclusion
There were clear associations between metabolic factors and RKOA in individuals with knee pain, also in those with normal BMI. In individuals with obesity age was the only variable associated to RKOA.
Trial registration
clinicalTrials.gov Identifier: NCT04928170.
... The statement of Niu et al. was supported by the results of a study conducted by Morović-Vergles et al., which stated that BMI had a strong association with the prevalence of hypertension in osteoarthritis patients [26]. In contrast to research conducted by Monira Hussain et al., who noted that the relationship between hypertension and osteoarthritis remained significant both before an adjustment and after adjustment for BMI [27]. ...
Hypertension has been known as one of the leading causes of death in Indonesia. Its major complications such as cerebrovascular accidents and heart disease are frequently associated with morbidity and disability. Recently, some research reports that hypertension had associated with the incidence of osteoarthritis. However, numerous researchers had disapproved of this theses and many research were conducted. To clarify this controversy, we conducted a small study to determine the relationship between the incidence of osteoarthritis in hypertensive patients. This study used an observational analytic study with a cross-sectional design. Purposive sampling method was used and obtain 50 peoples in Cempaka Health Centre of Banjarbaru chosen as the sample. Among them were 46 patients (92%) who had hypertension and 21 patients (42%) who had osteoarthritis. Hypertensive patients with osteoarthritis were 20 patients (40%), which is more than those without hypertension, as many as 1 patients (2%). Analysis using the fisher’s exact test obtained p=0.630 with a confidence level of 95%. Based on the research conducted it can be concluded that hypertension had not been associated with the incidence of osteoarthritis.
... P = 0.01) 144 . Although some studies neither confirmed these findings after adjustment for BMI 145,146 nor detected an association between T2DM and prevalence or incidence of OA 147,148 , some of the studies included in the meta-analysis reported the same increased risk after BMI adjustment, suggesting that T2DM is an independent risk factor for OA development 143 . For example, ultrasonography-detected synovitis and effusion were higher in patients with T2DM and end-stage knee OA who underwent arthroplasty than in those without T2DM, independent of patient BMI 143 . ...
Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. Synovial inflammation is present in the OA joint and has been associated with radiographic and pain progression. Several OA risk factors, including ageing, obesity, trauma and mechanical loading, play a role in OA pathogenesis, likely by modifying synovial biology. In addition, other factors, such as mitochondrial dysfunction, damage-associated molecular patterns, cytokines, metabolites and crystals in the synovium, activate synovial cells and mediate synovial inflammation. An understanding of the activated pathways that are involved in OA-related synovial inflammation could form the basis for the stratification of patients and the development of novel therapeutics. This Review focuses on the biology of the OA synovium, how the cells residing in or recruited to the synovium interact with each other, how they become activated, how they contribute to OA progression and their interplay with other joint structures.
... Ce syndrome regroupe des facteurs provoquant des dérégulations métaboliques comme l'obésité, le diabète, l'insulino-résistance, la dyslipidémie et l'hypertension(Kassi et al. 2011). Le MetS augmente le risque d'arthrose sans distinction entre les différentes localisations(Puenpatom and Victor 2009;Monira Hussain et al. 2014).L'association de plusieurs désordres métaboliques a un effet cumulatif et négatif sur l'apparition et le développement de l'arthrose. Parmi ces troubles, l'obésité, caractérisée par un indice de masse corporelle (IMC) supérieur à 30 constitue un risque majeur de développement de l'arthrose. ...
L’arthrose se caractérise par une dégradation du cartilage, une inflammation de la membrane synoviale et un remodelage osseux. L’inflammation présente dans l’arthrose induit la libération des alarmines (damage associated molecular pattern : DAMPS). Ces molécules sont libérées dans le milieu extracellulaire en cas de lésions tissulaires ou de stress et se lient aux récepteurs Toll Like (TLR2, TLR4) exprimés par les cellules de l’immunité innée. Le laboratoire a identifié la protéine 14-3-3ε qui partage de nombreuses caractéristiques avec les alarmines. L’objectif de ce travail est de déterminer le rôle d’alarmine de 14-3-3ε dans l’arthrose en étudiant ses effets sur les différents types cellulaires de l’articulation ; les chondrocytes, macrophages et synoviocytes fibroblast like et déterminer si les récepteurs de l’immunité innée, TLR2 et TLR4 sont impliqués dans son action. La protéine 14-3-3ε recombinante induit des effets pro-inflammatoires sur les explants de membranes synoviales humaines ainsi que sur les deux types cellulaires qui la composent, les synoviocytes et macrophages. Elle polarise les macrophages vers un phénotype pro-inflammatoire M1. L’inhibition ou l’absence de TLR2 et TLR4 dans des cultures de chondrocytes ou macrophages murins et humains provoque une diminution significative des effets de 14-3-3ε. L’ensemble de ces résultats désigne la protéine 14-3-3ε comme une nouvelle alarmine impliquée dans l’arthrose. L’identification de nouvelles alarmines et la compréhension de leurs mécanismes physiopathologiques représentent de potentielles stratégies thérapeutiques dans l’arthrose.
... Le terme « d'arthrose métabolique » prend de plus en plus de la place du fait de son association au syndrome métabolique. Chez les sujets obèses, l'accumulation d'autres anomalies métaboliques telles que l'hypertension artérielle, la dyslipidémie ou le diabète, majore le risque d'avoir une gonarthrose ou une arthrose digitale [38]. L'étude des facteurs dans notre travail montre une importante corrélation entre l'arthrose et l'HTA, le diabète. ...
Introduction. Le processus d’initiation de l’arthrose relève de plusieurs facteurs parmi lesquels l’obésité occupe une place importante expliquant l’individualisation récente du concept d’arthrose métabolique. Nos objectifs étaient d’évaluer le statut pondéral des patients arthrosiques en milieu de Médecine Interne au Sénégal et d’analyser les éventuelles comorbidités associées à l’arthrose. Patients et méthodes : Une étude transversale et descriptive, de juin 2016 à février 2017, a inclus les patients suivis pour une arthrose primitive quel qu’en soit la localisation aux services de Médecine Interne de l’Hôpital Aristide Le Dantec et de l’Hôpital Principal de Dakar. Les données sociodémographiques, les aspects de l’arthrose, les mesures anthropométriques et les comorbidités ont été recueillis et analysés à l’aide du logiciel Sphinx Plus2 Excel. Résultats : Cent quatorze patients ont été inclus ; leur âge moyen était de 60,16 ans (extrêmes de 39 et de 94 ans) avec un sex-ratio de 0,16 (98 femmes). La localisation de l’arthrose était le genou (71,9 %), le rachis (50 %), l’épaule (5 %), la hanche (4 %), les pieds (3 %) et les mains (3 %). L’IMC moyen était de 28,97 Kg/m2 avec 30,7 % des patients en surpoids et 33,1 % en obésité. L’obésité était notée chez 47 % des patients atteints de gonarthrose et 35,5 % de lombarthrose. L’obésité abdominale concernait 64 % des femmes et 30 % des hommes. L’hypertension artérielle, le diabète et l’hypercholes-térolémie étaient observés respectivement chez 42, 10 et 6 % des patients. Conclusion : la surcharge pondérale, l’obésité et les autres facteurs de risque cardiovasculaires sont des situations fréquentes chez les patients arthrosiques vus dans les services de Médecine Interne au Sénégal. Ces constatations rappellent l’importance des mesures hygiéno-diététiques dans la prise en charge et la prévention de l’arthrose.
... OA has generally been considered as a degenerative joint disease characterized by structural damage in the articular cartilage; however, OA is, in fact, more complex and heterogeneous involving cartilage, bone, and synovium further affected by multiple biomechanical and biochemical factors. With regard to these numerous factors, there is growing evidence that obesity and metabolic syndromes are associated with OA [1,2]. Reports of increased OA risk in non-weight bearing joints of obese patients suggest that metabolic factors can cause the perpetuation of OA [3,4]. ...
... Интересно, что после поправки результатов исследования на индекс массы тела (ИМТ) или вес пациентов определялась сильная корреляция АГ с выраженностью симптоматических и рентгенологических проявлений ОА. Кроме того, Hussain SM, et al. (2014г) [13] показали, что увеличение числа компонентов МС повышает вероятность эндопротезирования коленного сустава при ОА независимо от ИМТ: один компонент -относительный риск (ОР) =2,12; 95% доверительный интервал (ДИ): 1,15-3,91; два компонен-та -ОР 2,92; 95% ДИ: 1,60-5,33 и/или ≥3 компонентов -ОР 3,09; 95% ДИ: 1,68-5,69. В 3-летнем наблюдательном исследовании ROAD (Research on Osteoarthritis/Os teoporosis Against Disability) [14] также была опре делена роль кумуляции компонентов МС в развитии ОА. ...
A critical analysis of the study’s results on the relationship of cardiovascular diseases and osteoarthritis is carried out. An assessment of the possibility of their combined prevention and treatment is given. The analysis of experimental, clinical and large-scale studies of recent years allows to put forward a well-founded concept, according to which the joint tissues are the target organ for a number of cardiovascular factors. Hypertension, hyperlipidemia, and obesity are among the most significant risk factors for degenerative joint diseases. In a number of studies, the primary role of these factors in the pathogenesis of osteoarthritis has been established, and therefore an attempt has been made to clinically classify cardiovascular comorbidity in osteoarthritis. Currently, there are reasons to believe that active non-pharmacological and pharmacological correction of cardiovascular factors can be used in the treatment of osteoarthritis.
... This is consistent with a recent meta-analysis that reported an increased risk of diabetes in patients with knee OA but not for hip OA [46]. This difference might likely be largely explained by stronger association between obesity and knee OA as compared with hip OA, and thus metabolic factors associated with obesity [47,48]. ...
Objective
To determine the association between osteoarthritis (OA) and risk of hospitalization for ambulatory care sensitive conditions (HACSCs).
Methods
We included all individuals aged 40–85 years who resided in Skåne, Sweden on 31st December 2005 with at least one healthcare consultation during 1998–2005 (n = 515 256). We identified those with a main diagnosis of OA between January 1, 1998 and December 31, 2016. People were followed from January 1st 2006 until an HACSC, death, relocation outside Skåne, or December 31st 2016 (whichever occurred first). OA status was treated as a time-varying covariate (those diagnosed before January 1, 2006 considered as exposed for whole study period). We assessed relative (hazard ratios (HRs) using Cox proportional hazard model) and absolute (hazard difference using additive hazard model) effects of OA on HACSCs adjusted for potential confounders.
Results
Crude incidence rates of HACSCs were 239 (95% CI 235, 242) and 151 (150, 152) per 10 000 person-years among OA and non-OA persons, respectively. The OA persons had an increased risk of HACSCs (HR [95% CI] 1.11 [1.09, 1.13]) and its subcategories of medical conditions except chronic obstructive pulmonary disease (HR [95% CI] 0.86 [0.81, 0.90]). There were 20 (95% CI 16, 24) more HACSCs per 10 000 person-years in OA compared with non-OA persons. While HRs for knee and hip OA were generally comparable, only knee OA was associated with increased risk of hospitalization for diabetes.
Conclusion
OA is associated with an increased risk of HACSCs, highlighting the urgent need to improve outpatient care for OA patients.
... The results from longitudinal studies are equally contradictory [32,34]. Similarly, some studies have shown a positive association between hypertension and radiographic knee OA [35][36][37], while others found no associations [38,39]. In addition, we found no mediation by aorta PWV, which is in line with a lack of association of PWV with OA observed previously [40,41]. ...
Objective
We investigated the role of blood pressure, vessel wall stiffness [pulse wave velocity (PWV)] and subclinical atherosclerosis markers [carotid intima-media thickness (cIMT), popliteal vessel wall thickness (pVWT)] as mediators of the association of obesity with OA.
Methods
We used cross-sectional data from a subset of the population-based NEO study (n = 6334). We classified clinical hand and knee OA by the ACR criteria, and structural knee OA, effusion and bone marrow lesions on MRI (n = 1285). cIMT was assessed with ultrasonography. pVWT was estimated on knee MRI (n = 1285), and PWV by abdominal velocity-encoded MRIs (n = 2580), in subpopulations. Associations between BMI and OA were assessed with logistic regression analyses, adjusted for age, sex and education. Blood pressure, cIMT, pVWT and PWV were added to the model to estimate mediation.
Results
The population consisted of 55% women, with a mean (s.d.) age of 56(6) years. Clinical hand OA was present in 8%, clinical knee OA in 10%, and structural knee OA in 12% of participants. BMI was positively associated with all OA outcomes. cIMT partially mediated the association of BMI with clinical hand OA [10.6 (6.2; 30.5)%], structural knee OA [3.1 (1.9; 7.3)%] and effusion [10.8 (6.0; 37.6)%]. Diastolic blood pressure [2.1 (1.6; 3.0)%] minimally mediated the association between BMI and clinical knee OA. PWV and pVWT did not mediate the association between BMI and OA.
Conclusions
cIMT and diastolic blood pressure minimally mediated the association of BMI with OA. This suggests that such mediation is trivial in the middle-aged population.
... Postmenopausal women are more susceptible to knee arthritis because of their increased levels of calcitonin and bone resorption. However, there is some evidence that the loss of estrogen could be a contributing factor [30]. ...
Osteoarthritis (OA) is the most well-known degenerative disease among the geriatric and is a main cause of significant disability in daily living. It has a multifactorial etiology and is characterized by pathological changes in the knee joint structure including cartilage erosion, synovial inflammation, and subchondral sclerosis with osteophyte formation. To date, no efficient treatment is capable of altering the pathological progression of OA, and current therapy is broadly divided into pharmacological and nonpharmacological measures prior to surgical intervention. In this review, the significant risk factors and mediators, such as cytokines, proteolytic enzymes, and nitric oxide, that trigger the loss of the normal homeostasis and structural changes in the articular cartilage during the progression of OA are described. As the understanding of the mechanisms underlying OA improves, treatments are being developed that target specific mediators thought to promote the cartilage destruction that results from imbalanced catabolic and anabolic activity in the joint.
... Hence, an ACL-related injury preventive program should be supported, since incapability of complete recovery from ACL injury usually results in worsening of the pathogenesis (7). By providing fundamental information on the association of physiological markers such as body mass index (BMI), blood pressure (BP), and waist circumference (Waist), associated with OA (8)(9)(10)(11), this study can provide the basis for an effective knee injury preventive program. The role of different modalities of exercise and specific markers in ACL pathogenesis and cure is not clear. ...
Background:
Knee disease is prevalent in the post middle-aged and associated with lower quality of life. Knee disease (i.e., anterior cruciate ligament, ACL) related injury preventive program should be supported. We examined the significant effect of different age, gender, and exercise modalities on measureable nine dependent markers in National Health Insurance Sharing Service database (NHISS DB) registered ACL patients using big data analysis.
Methods:
The 1755 ACL patients from 514,866 in NHISS DB have been randomly selected by retrospective cohort study using big data from 2002 to 2013. Six independent and 9 dependent variables were used for analyzing patients with ACL injuries by T-test and Two-way analysis of variance (ANOVA).
Results:
Mean (SD) (men vs. women) of BMI, high blood pressure (BP), serum glutamic oxaloacetic transaminase (SGOT), and total cholesterol were 24.38±2.72 vs. 24.86±3.12 (P<0.01, 95% C.I., -0.763 ∼ -0.194), 126.64±14.70 vs. 125.02±16.62 (P<0.05, 95% C.I., 0.104 ∼ 3.151), 27.63±12.18 vs. 24.27±8.48 (P<0.01, 95% C.I., 2.393 ∼ 4.331), 197.77±37.60 vs. 205.72±36.72 (P<0.01, 95% C.I., -11.533 ∼ -4.378), respectively. Age and the frequency of 20 min severe exercise per week (Move20_Freq) intensive exercise had a significant association with BMI (P<0.05). Gender and Move20_Freq had a significant association with BP (P<0.05).
Conclusion:
Age-dependent Move20_Freq is associated with BMI in ACL patients. Women with ACL have higher BMI and cholesterol levels than men. These gender-specific differences can be relieved by exercise.
... The presence of atherosclerosis has been associated with an increased risk of OA [81] that may suggest that abnormal perfusion of subchondral bone, which is only generally seen in atherosclerosis, could be a plausible mechanism for OA disease progression in these patients [78]. Hypertension has also been associated with an increased risk of OA [82,83] and with more severe OA [69]; however, the risk of hypertension is also higher in patients with OA [84]. Lipid disorders, such as dyslipidemia [85] and higher levels of low-density lipoprotein cholesterol [86,87], are also associated with an increased risk of OA. ...
Globally, osteoarthritis (OA) is the most prevalent arthritic condition in those aged over 60 years. OA has a high impact on patient disability and is associated with a significant economic burden. Pain is the most common first sign of disease and the leading cause of disability. Data demonstrating the increasing global prevalence of OA, together with a greater understanding of the burden of the disease, have led to a reassessment of the seriousness of OA and calls for the designation of OA as a serious disease in line with the diseases impact on comorbidity, disability, and mortality.
While OA was traditionally seen as a prototypical ‘wear and tear’ disease, it is now more accurately thought of as a disease of the whole joint involving cartilage together with subchondral bone and synovium. As more has become known of the pathophysiology of OA, it has become increasingly common for it to be described using a number of overlapping phenotypes. Patients with OA will likely experience multiple phenotypes during their disease. This review focuses on what we feel are three key phenotypes: post-trauma, metabolic, and aging. A greater understanding of OA phenotypes, particularly at the early stages of disease, may be necessary to improve treatment outcomes. In the future, non-pharmacological and pharmacological treatments could be tailored to patients based on the key features of their phenotype and disease pathway.
... Metabolic syndrome (MetS), generally consisting of increased waist circumference, dyslipidaemia (elevated triglycerides and reduced high-density lipoprotein (HDL)), hypertension and elevated serum glucose, has shown a relatively consistent association with the development and progression of OA 7e12 and joint replacement 13,14 before adjustment for body mass index (BMI) in previous studies, although the positive associations between MetS and its components and OA disappeared or weakened after controlling for BMI. Furthermore, most prior studies have been cross-sectional, limiting the ability to determine causality and raising the possibility that OA and MetS simply co-exist through shared risk factors such as age and obesity. ...
Objectives:
To examine the association of metabolic syndrome (MetS) and its components with knee pain severity trajectories.
Methods:
Data from a population-based cohort study were utilised. Baseline blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) cholesterol were measured. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. Radiographic knee osteoarthritis (ROA) was assessed by X-ray. Pain severity was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain questionnaire at each time-point. Group-based trajectory modelling was used to identify pain trajectories and multi-nominal logistic regression was used for analysis. Mediation analysis was performed to assess whether body mass index (BMI)/central obesity mediated the association between MetS, its components and pain trajectories.
Results:
Among 985 participants (Mean ± SD age: 62.9 ± 7.4, 50% female), 32% had MetS and 60% had ROA. Three pain trajectories were identified: 'Minimal pain' (52%), 'Mild pain' (33%) and 'Moderate pain' (15%). After adjustment for potential confounders, central obesity increased risk of belonging to both 'Mild pain' and 'Moderate pain' trajectories as compared to the 'Minimal pain' trajectory group, but MetS [relative risk ratio (RRR): 2.26, 95%CI 1.50-3.39], hypertriglyceridemia (RRR: 1.75, 95%CI 1.16-2.62) and low HDL (RRR: 1.67, 95%CI 1.10-2.52) were only associated with 'Moderate pain' trajectory. BMI/central obesity explained 37-70% of these associations. Results were similar in those with ROA.
Conclusion:
MetS and its components are predominantly associated with worse pain trajectories through central obesity, suggesting that the development and maintenance of worse pain trajectories may be caused by MetS.
... However, there is growing evidence to suggest a possible link between systemic inflammation and OA progression [79] and to consider metabolic OA as a new OA phenotype [10,11]. Metabolic syndrome (MetS), defined as a cluster of disorders including central obesity, diabetes and insulin resistance, hypertension and dyslipidaemia, is associated with the development and progression of OA [1218] and joint replacement [19,20] before or even after controlling for body fatness in previous studies. Although there is a relatively consistent association between central obesity and OA, the results for other components of MetS are conflicting. ...
Objective:
To examine the association of metabolic syndrome (MetS) and its components with knee cartilage volume loss and bone marrow lesion (BML) change.
Methods:
Longitudinal data on 435 participants from a population-based cohort study were analysed. Blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) were collected. MetS was defined based on the National Cholesterol Education Program-Adult Treatment Panel III criteria. MRI of the right knee was performed to measure cartilage volume and BML. Radiographic knee OA was assessed by X-ray and graded using the Altman atlas for osteophytes and joint space narrowing.
Results:
Thirty-two percent of participants had MetS and 60% had radiographic knee OA. In multivariable analysis, the following were independently associated with medial tibial cartilage volume loss: MetS, β = -0.30%; central obesity, β = -0.26%; and low HDL, β = -0.25% per annum. MetS, hypertriglyceridaemia and low HDL were also associated with higher risk of BML size increase in the medial compartment (MetS: relative risk 1.72, 95% CI 1.22, 2.43; hypertriglyceridaemia: relative risk 1.43, 95% CI 1.01, 2.02; low HDL: relative risk 1.67, 95% CI 1.18, 2.36). After further adjustment for central obesity or BMI, MetS and low HDL remained statistically significant for medial tibial cartilage volume loss and BML size increase. The number of components of MetS correlated with greater cartilage volume loss and BML size increase (both P for trend <0.05). There were no statistically significant associations in the lateral compartment.
Conclusion:
MetS and low HDL are associated with medial compartment cartilage volume loss and BML size increase, suggesting that targeting these factors has the potential to prevent or slow knee structural change.
... Osteoarthritis is a common orthopaedic condition affecting many joints of the body, most commonly the knee, hip and hand, that typically results in joint pain, stiffness and swelling [62] and which may ultimately become so severe that joint replacements are required [63]. With respect to the upper body, the reductions in forearm and hand muscle mass and strength as well as the increased level of joint pain, stiffness and swelling may contribute to significant declines in upper limb fine motor control [64]. ...
Background
The ageing process and several health conditions may increase tremor and reduce force steadiness and dexterity, which can severely impact on function and quality of life. Resistance training can evoke a range of neuromuscular adaptions that may significantly reduce tremor and/or increase force steadiness and/or dexterity in older adults, irrespective of their health condition.
Objectives
The objective of this study was to systematically review the literature to determine if a minimum of 4 weeks’ resistance training can reduce postural tremor and improve force steadiness and/or dexterity in older adults, defined as aged 65 years and over.
Methods
An electronic search using Ovid, CINAHL, SPORTDiscus and EMBASE was performed. Risk of bias was assessed using the Cochrane Risk of Bias Tool.
Results
Fourteen studies met the eligibility criteria, including six randomised controlled trials and two quasi-randomised controlled trials. All eight studies that recruited healthy older adults reported significant reductions in postural tremor and/or improvements in force steadiness and dexterity. Five out of seven studies that examined older adults with a particular health condition reported some improvements in force steadiness and/or dexterity. Specifically, significant benefits were observed for older adults with chronic obstructive pulmonary disease and essential tremor; however, small or no changes were observed for individuals with osteoarthritis or stroke.
Conclusions
Resistance training is a non-pharmacological treatment that can reduce tremor and improve force steadiness and dexterity in a variety of older adult populations. Future research should employ randomised controlled trials with larger sample sizes, better describe training programme methods, and align exercise prescription to current recommendations for older adults.
... Moreover, OA is associated with the increased prevalence of MetS and its components, particularly in young individuals 22 . Regardless of some controversial findings 23,24 , the bona fide association between MetS and OA phenotypic outcomes is generally accepted, as this link persists after the body weight or body mass index is adjusted 22,25 . Metabolic OA has even been proposed as a new criterion for the definition of MetS, which is supported by shared pathogenic mechanisms, such as inflammation, in the etiologies of MetS and OA 26 . ...
Obesity is a well-known primary risk factor for osteoarthritis (OA). In recent decades, the biomechanics-based theoretical paradigm for the pathogenesis of obesity-associated OA has been gradually but fundamentally modified. This modification is a result of accumulating evidence that biological factors also contribute to the etiology of the disease. The gut microbiota is a complicated ecosystem that profoundly influences the health of the host and can be modulated by the combined effects of environmental stimuli and genetic factors. Recently, enteric dysbacteriosis has been identified as a causal factor in the initiation and propagation of obesity-associated OA in animal models. Gut microbes and their components, microbe-associated lipid metabolites, and OA interact at both systemic and local levels through mechanisms that involve interplay with the innate immune system. However, the demonstration of causality in humans will require further studies. Nonetheless, probiotics, prebiotics, dietary habits and exercise, which aid the restoration of a healthy microbial community, are potential therapeutic approaches in the treatment of obesity-associated OA.
... 10%男性和18%女性正遭受骨关节炎影响。据估计， 骨关节炎的医疗费用占一个国家国内生产总值的 0.25%~0.5% [4] 。因此，骨关节炎已越来越被公众认为 是造成国家医疗卫生与社会经济负担的主要问题来 源，也是造成人群发病与致残的主要原因 [5][6] 。 近年来，骨关节炎被分成3个亚型：年龄相关的 骨关节炎、损伤相关的骨关节炎以及代谢相关的骨 关节炎 [7] 。研究 [8][9][10][11][12] 发现：高血压不仅是心血管疾病 和慢性肾病最重要的危险因素，其也可能与骨关节 炎患病存在正相关。除此之外，部分研究 [13][14][15] ...
Objective:
To examine the association between serum copper concentration and the prevalence of hypertension in patients with knee osteoarthritis (OA).
Methods: A total of 935 patients who were aged ≥40 years and underwent routine checkups from October 2013 to November 2014 at the Health Management Center of Xiangya Hospital, Central South University were included. They were diagnosed as knee OA by weight-bearing bilateral anteroposterior radiography. Serum copper concentration was measured using the chemiluminescence method. Blood pressure was measured by an electronic sphygmomanometer. The association between serum copper concentration and hypertension was evaluated by conducting multivariable adjusted logistic regression.
Results: Compared with the lowest quintile, the multivariable-adjusted odds ratio (OR) and related 95% confidence interval (95% CI) of hypertension were 1.46 (95% CI 1.02 to 2.09, P for trend=0.035) and 1.47 (95% CI 0.77 to 2.78, P for trend=0.032) in the total population and female subgroup of the highestest quintile, respectively. There was no significant association between serum copper and hypertension in male subgroup among OA patients (OR=1.21, 95% CI 0.76 to 1.93, P for trend=0.354).
Conclusion: The serum copper concentration was significantly associated with the prevalence of hypertension in total population and female subgroup, but may not in male subgroup among patients with knee OA.
To examine the sex differences in the relationship of metabolic syndrome (MetS) criteria with arthritis and symptomatic arthritis among Mexican American older adults aged ≥ 65 without self-reported arthritis at baseline over 23-years of follow-up.
Participants (N = 1447) were from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1993/94–2016). Measures included MetS criteria, arthritis defined as self-reported physician-diagnosed arthritis, socio-demographics, morbidities, depressive symptoms, pain on weight-bearing, cognitive and physical function, handgrip strength, mobility, and activities of daily living (ADLs) limitations. Symptomatic arthritis was defined as self-reported arthritis and having ≥ 1 of the following: pain, mobility limitation, or limited ADLs.
At baseline, the mean age was 72.6 years and 730 (50.5%) of our participants were females. Female participants with 2 and 3 MetS criteria had greater odds of arthritis [odds ratio (OR) = 1.77, 95% Confidence Interval (Cl) = 1.28–2.45 and OR = 2.68, 95% CI = 1.69–4.27, respectively) and symptomatic arthritis (OR = 1.74, 95% Cl = 1.24–2.44 and OR = 3.27, 95% CI = 2.04–5.26, respectively) after controlling for covariates. Male participants with 2 and 3 MetS criteria had greater odds of arthritis (OR = 1.65, 95% Cl = 1.14–2.39 and OR = 2.52, 95% CI = 1.51–4.19, respectively) and symptomatic arthritis (OR = 1.93, 95% Cl = 1.30–2.86 and OR = 2.98, 95% CI = 1.62–5.47, respectively) after controlling for covariates. Both females and males with pain on weight-bearing had greater odds of arthritis than those without pain.
At 23-years of follow-up, Mexican American older adults with MetS have an increased risk of arthritis and symptomatic arthritis. Early MetS screening and management may reduce arthritis in this population at high risk of disability.
Background
Changes in lifestyle habits can reduce morbidity and mortality, but not everyone who can benefit from lifestyle intervention is ready to do so.
Purpose
To describe characteristics of patients who did and did not engage with a lifestyle medicine program, and to identify predictors of engagement.
Methods
This was a single-center, retrospective cohort study of 276 adult patients who presented for consultation to a goal-directed, individualized, interprofessional lifestyle medicine program. The primary outcome was patients’ extent of engagement. Candidate predictors considered in multivariable multinomial logistic regression models included baseline sociodemographic, psychological, and health-related variables.
Results
A predictor of full engagement over no engagement was having private or Medicare insurance (rather than Medicaid, other, or no insurance) (OR 4.2 [95% CI 1.3-14.2], P = .021). A predictor of partial engagement over no engagement was having a primary goal to lose weight (OR 3.1 [1.1-8.4], P = .026).
Conclusions
System-level efforts to support coverage of lifestyle medicine services by all insurers may improve equitable engagement with lifestyle medicine programs. Furthermore, when assessing patients’ readiness to engage with a lifestyle medicine program, clinicians should consider and address their goals of participation.
Background
Therapeutic lifestyle change can be challenging, and not every attempt is successful.
Purpose
To identify predictors of making progress toward lifestyle change among patients who participate in a lifestyle medicine program.
Methods
This was a single-center, retrospective cohort study of 205 adults who enrolled in a goal-directed, individualized, interprofessional lifestyle medicine program. The primary outcome was whether, by the end of participation with the program, a patient reported making progress toward lifestyle change. Candidate predictors included sociodemographic, psychological, and health-related variables.
Results
Among 205 patients (median (IQR) age 58 (44-66) years, 164 (80%) female), 93 (45%) made progress toward lifestyle change during program participation. A predictor of making progress was being motivated by stress reduction (OR 2.8 [95% CI 1.1-7.6], P = .038). Predictors of not making progress included having a primary goal of losing weight (OR .3 [.2-.8], P = .012) and having a history of depression (OR .4 [.2-.7], P = .041).
Conclusions
To maximize a patient’s likelihood of successfully making lifestyle changes, clinicians and patients may consider focusing on identifying goals that are immediately and palpably affected by lifestyle change. Additional research is warranted to identify effective program-level approaches to maximize the likelihood of success for patients with a history of depression.
Endocrinopathies affect multiple species in ever-increasing percentages of their populations, creating an opportunity to apply one-health approaches to determining creative preventative measures and therapies in athletes. Obesity and alterations in insulin and glucose dynamics are medical concerns that play a role in whole-body health and homeostasis in both horses and humans. The role and impact of endocrine disorders on the musculoskeletal, cardiovascular, and reproductive systems are of particular interest to the athlete. Elucidation of both physiologic and pathophysiologic mechanisms involved in disease processes, starting in utero, is important for development of prevention and treatment strategies for the health and well-being of all species. This review focuses on the unrecognized effects of endocrine disorders associated with the origins of metabolic disease; inflammation at the intersection of endocrine disease and related diseases in the musculoskeletal, cardiovascular, and reproductive systems; novel interventions; and diagnostics that are informed via multiomic and one-health approaches. Readers interested in further details on specific equine performance conditions associated with endocrine disease are invited to read the companion Currents in One Health by Manfredi et al, JAVMA, February 2023.
Background:
Knee osteoarthritis (KOA) is a chronic degenerative pathology that is associated with multiple risk factors such as age, sex, obesity, or metabolic syndrome (MetS). The present clinical trial aimed to investigate the influence of the environment of origin, body mass index (BMI), and MetS parameters on the KOA differentiated degrees.
Methods:
85 patients were admitted for the clinical study. The KOA presence was investigated using X-rays analysis. The Kellgren-Lawrence classification (KL) of the KOA severity and the MetS characteristic parameters using freshly collected blood were performed for each patient. All data collected were used for ANOVA statistic interpretation.
Results:
The total cholesterol and glycemia were found to be statistically significant (p < 0.028, and p < 0.03, respectively), with a high level in patients with severe KOA compared to healthy ones. Patients from rural regions are 5.18 times more prone to develop severe KOA when compared to ones from urban areas.
Conclusions:
The results of the statistical analysis confirmed the correlation between the incidence and severity of KOA and the influence of increased values of BMI, glycemia, triglycerides, and total cholesterol. The investigations revealed a statistically significant influence of the environment of origin on the KOA degree of the patients.
Background: Only few studies have explored whether BMI across life is associated with knee OA. The aim of this study was to examine if the risk of knee arthroplasty related to adult BMI is modified by early lifetime overweight.
Methods: A total of 22 083 female nurses were followed from 1st of May 1999 until 10th of August 2015, date of knee arthroplasty or censoring (emigration, end of study or death). At baseline participants completed a questionnaire on different lifestyle-related factors. Knee arthroplasty events were identified through linkage to the Danish National Patient Register. The association was examined using Poisson regression of incidence rate of knee arthroplasty.
Results: A direct association was found between BMI and rate of knee arthroplasty. The largest difference in the incidence rate of knee arthroplasty per unit increase in BMI was seen among women with no early lifetime overweight (IRR: 1.15, 95% CI: 1.13; 1.17), while the smallest difference was seen among women with early lifetime overweight (IRR: 1.09, 95% CI: 1.06; 1.12).
Conclusion: Early lifetime overweight seems to modify the association between BMI and knee arthroplasty, suggesting a lower incidence rate for obese women with early lifetime overweight than obese women without early lifetime overweight.
In this chapter, the author presents a comprehensive review of the articular cartilage. The function, structure, and metabolism of the cartilage as integrant component of the joint are discussed. The readers can find an in-depth analysis of biomechanical behavior of the articular cartilage and the mechanism of cartilage degeneration. The link between osteoarthritis and diabetes is discussed as well as the risk factors associated with the advent of both conditions. A section of the chapter is dedicated to the triad—“diabetes, arthritis, and obesity.” The effects of diabetes (and hyperglycemia) on the cartilage and subchondral bones are included in the chapter. MR images of cartilage destruction and osteochondral lesions associated with diabetes Type 2 and Charcot neuroarthropathy are also provided.
Introduction:
Factors that motivate musculoskeletal patients to pursue an intensive, lifestyle medicine based approach to care are poorly understood.
Objective:
To determine whether, compared to patients seeking musculoskeletal care through traditional pathways, patients who choose an intensive lifestyle medicine program for musculoskeletal pain endorse greater physical dysfunction, worse psychological health, and/or more biopsychosocial comorbidities.
Design:
Cross-sectional analysis of existing medical records from 2018-2021.
Setting:
Orthopedic department of one academic medical center.
Patients:
Fifty consecutive patients who enrolled in an intensive lifestyle medicine program to address a musculoskeletal condition. Comparison groups were: 1.) 100 patients who presented for standard non-operative musculoskeletal care, and 2.) 100 patients who presented for operative evaluation by an orthopedic surgeon and qualified for joint arthroplasty.
Intervention:
Not applicable.
Main outcome measures:
Primary outcomes were age-adjusted, between-group differences in Patient-Reported Outcomes Measurement Information System (PROMIS) physical and psychological health measures. Secondary outcomes were between-group differences in sociodemographic and medical history characteristics.
Results:
Patients who enrolled in the intensive lifestyle medicine program were more racially diverse (non-white race: lifestyle cohort 34% versus comparison cohorts 16-18%, p≤.029) and had a higher prevalence of obesity and diabetes than both comparison groups (mean body mass index: lifestyle cohort 37.6 kg/m2 versus comparison cohorts 29.3-32.0, p<.001; diabetes prevalence: lifestyle cohort 32% versus comparison cohorts 12-16%, p≤.024). Compared to standard non-operative patients, there were no clear between-group differences in PROMIS physical or psychological health scores. Compared to standard operative evaluation patients, patients in the lifestyle program reported worse anxiety but less pain interference (PROMIS Anxiety: B=3.8 points [0.1-7.4], p=.041; Pain Interference: B=-3.6 [-6.0- -1.2], p=.004).
Conclusions:
Compared to musculoskeletal patients who sought care through traditional pathways, patients who chose an intensive lifestyle medicine pathway had a higher prevalence of metabolic comorbidities, but there was substantial overlap in patients' physical, psychological, and sociodemographic characteristics. This article is protected by copyright. All rights reserved.
Some studies have suggested that diabetes may be a risk factor for osteoarthritis. However, whether prediabetes is also associated with osteoarthritis has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoarthritis. This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Ten datasets from six observational studies were included, which involved 41 226 general adults and 10 785 (26.2%) of them were prediabetic. Pooled results showed that prediabetes was not independently associated with osteoarthritis [risk ratio (RR): 1.07, 95% confidence interval (CI): 1.00 to 1.14, p=0.06, I2=0%]. Sensitivity limited to studies with adjustment of age and body mass index showed consistent result (RR: 1.06, 95% CI: 0.99 to 1.14, p=0.09, I2=0%). Results of subgroup analyses showed that prediabetes was not associated with osteoarthritis in cross-sectional or cohort studies, in studies including Asian or non-Asian population, or in studies with different quality scores (p for subgroup difference>0.10). Besides, prediabetes was not associated with osteoarthritis in men or in women, in studies with prediabetes defined as impaired fasting glucose, impaired glucose tolerance, or HbA1c (approximately 39–46 mmol/mol). Moreover, prediabetes was not associated with overall osteoarthritis, and knee or hip osteoarthritis. Current evidence does not support that prediabetes is independently associated with osteoarthritis in adult population.
Hypertension was one common comorbidity of knee osteoarthritis (KOA), but the effect of different types of antihypertensive drugs on pain and joint space width (JSW) was unclear and not compared. Four hundred ninety KOA patients using one of the beta-blockers, ACE inhibitors, angiotensin receptor blockers, Calcium channel blockers (CCBs), or thiazide diuretics were followed for four years. The blood pressure, cumulative knee replacement rate, Womac pain, and JSW were compared among groups. All data were from the Osteoarthritis Initiative project. The CCBs group has the highest systolic blood pressure, replacement rate, and pain score at most visit timepoints. At baseline, the CCBs group was with significantly higher pain score than the beta-blockers group (3.3 vs 1.3, p < .05), the angiotensin receptor blockers group (3.3 vs 1.4, p < .05), and the thiazide diuretics group (3.3 vs 1.6, p < .05) in male; the CCBs group was with significantly higher pain score than the beta-blockers group (3.8 vs 2.0, p < .01), and the angiotensin receptor blockers group (3.8 vs 2.2, p < .05) in female. The results of females at 36 months were similar to the baseline. Among the common antihypertensive drugs, CCBs were associated with high replacement rates, high pain scores, and less JSW in KOA patients.
Objective
Obesity was once considered a risk factor for knee osteoarthritis (OA) primarily for biomechanical reasons. Here we provide an additional perspective by discussing how obesity also increases OA risk by altering metabolism and inflammation.
Design
This narrative review is presented in four sections: 1) metabolic syndrome and OA, 2) metabolic biomarkers of OA, 3) evidence for dysregulated chondrocyte metabolism in OA, and 4) metabolic inflammation: joint tissue mediators and mechanisms.
Results
Metabolic syndrome and its components are strongly associated with OA. However, evidence for a causal relationship is context dependent, varying by joint, gender, diagnostic criteria, and demographics, with additional environmental and genetic interactions yet to be fully defined. Importantly, some aspects of the etiology of obesity-induced OA appear to be distinct between men and women, especially regarding the role of adipose tissue. Metabolomic analyses of serum and synovial fluid have identified potential diagnostic biomarkers of knee OA and prognostic biomarkers of disease progression. Connecting these biomarkers to cellular pathophysiology will require future in vivo studies of joint tissue metabolism. Such studies will help reveal when a metabolic process or a metabolite itself is a causal factor in disease progression. Current evidence points towards impaired chondrocyte metabolic homeostasis and metabolic-immune dysregulation as likely factors connecting obesity to the increased risk of OA.
Conclusions
A deeper understanding of how obesity alters metabolic and inflammatory pathways in synovial joint tissues is expected to provide new therapeutic targets and an improved definition of “metabolic” and “obesity” OA phenotypes.
Background: Metabolic syndrome has been associated with poorer outcomes in the immediate postoperative period following joint replacement surgery for osteoarthritis. The aim of this study was to determine whether a multidisciplinary, preoperative intervention would minimize postoperative differences between people with and without metabolic syndrome who underwent joint replacement surgery for osteoarthritis. Method: A retrospective cohort study of older adults with multiple comorbidities (n = 230) attending a preoperative intervention service before lower limb joint replacement surgery. The intervention aimed to optimize the patient's health and functional reserve before surgery through weight loss, physical activity and medical management. Patient outcomes were adverse events, discharge destination and function. Health service outcomes were length of stay, hospital readmissions and emergency department presentations over a 2-year follow-up. Results: Two-thirds of participants (n = 151) had metabolic syndrome. There were no significant differences between those with and without metabolic syndrome in terms of discharge destination or adverse events during the acute hospital admission. There were no differences in function during rehabilitation but people with metabolic syndrome had significantly more adverse events (P = 0.037) during rehabilitation. In the 2 years following surgery, there were no differences in hospital readmission rates but people with metabolic syndrome had a higher observed frequency of potentially avoidable emergency department presentations (P = 0.066). Conclusions: Providing a preoperative intervention may help minimize differences between people with and without metabolic syndrome in the immediate postoperative period. However, having a diagnosis of metabolic syndrome may still adversely affect some long-term health service outcomes following joint replacement surgery.
Objective
Metabolic syndrome (MetS) is a clustering of at least three of the following four medical conditions: obesity, hypertension, dyslipidemia, and hyperglycemia. We aimed to discover the relationships between these diseases and osteoarthritis (OA) of the knee.Methods
We searched four databases (EMBASE, PubMed, Cochrane Library, and MEDLINE), as well as articles on websites and conference materials. Study effect estimates and their 95% confidence intervals (CIs) were extracted and calculated. Sensitivity analyses were undertaken to determine inter-study heterogeneity. Finally, we tested for publication bias to determine whether the outcome of the meta-analysis was robust.ResultsA total of 1609 articles were identified, 40 of which were included. In radiological studies, the relationships with OA were increased for people with the following diseases: metabolic syndrome (OR 1.418, 95% CI 1.162 to 1.730), hypertension (OR 1.701, 95% CI 1.411 to 2.052), and hyperglycemia (OR 1.225, 95% CI 1.054 to 1.424). In symptomatic studies, the outcomes were similar in metabolic syndrome (OR 1.174, 95% CI 1.034 to 1.332) and hypertension (OR 1.324, 95% CI 1.186 to 1.478) studies, while there were no associations in hyperglycemia (OR 0.975, 95% CI 0.860 to 1.106) studies. There was no correlation between dyslipidemia and OA, whether in radiological studies (OR 1.216, 95% CI 0.968 to 1.529) or symptomatic studies (OR 1.050, 95% CI 0.961 to 1.146).Conclusions
In both studies, metabolic syndrome and hypertension were positively associated with knee OA, and dyslipidemia showed no correlations. Hyperglycemia was associated with OA in radiological studies, while results were reversed in symptomatic studies.
Key Points
• The hypothesis that metabolic syndrome and its components increase the risk for knee osteoarthritis is attractive; thus, this meta-analysis may help us find out the answer.
• There were lots of large-scale studies here, and the total participants were considerable; and this meta-analysis was relatively robust because of reasonable heterogeneity and publication bias.
• Targeted education and effective management of risk factors may be helpful for reducing the prevalence of knee osteoarthritis.
Objective
The objective of the study was to determine whether statin use could reduce the risk of the incidence or progression of osteoarthritis (OA).
Methods
The PubMed, Embase, and Cochrane databases were systematically searched for observational studies on the association between statin use and OA. ORs and 95% CIs were directly retrieved or calculated. The Newcastle-Ottawa quality assessment scale was used for study quality assessment. Subgroup analysis, sensitivity analysis, and publication bias were conducted using Stata software.
Results
A total of 11 studies (679807 participants) were identified from the systematic literature search. No significant association between statin use and incidence (OR = 1.010; 95% CI: 0.968 to 1.055; P = 0.638) or progression (OR = 1.076; 95% CI: 0.824 to 1.405; P = 0.589) of OA was found in our meta-analysis. The meta-analysis according to the symptomatic or radiological OA also found no significant association between statin use and OA. The subgroup analysis showed that atorvastatin (OR = 0.953; 95% CI: 0.911 to 0.998; P = 0.041) and rosuvastatin (OR = 1.180; 95% CI: 1.122 to 1.241; P < 0.0001) had opposite effects on OA. The results of the analysis according to the joint site, interval, and statin dose were all not significant.
Conclusions
Statin use may not be associated with a lower risk of incidence and progression of OA, regardless of joint site. The opposite effects of atorvastatin and rosuvastatin were detected in OA.
Objective
To investigate the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with changes in knee cartilage composition and joint structure over 48 months, using magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative (OAI).Materials and methodsA total of 1126 participants with right knee Kellgren-Lawrence (KL) score 0–2 at baseline, no history of rheumatoid arthritis, blood pressure measurements at baseline, and cartilage T2 measurements at baseline and 48 months were selected from the OAI. Cartilage composition was assessed using MRI T2 measurements, including laminar and gray-level co-occurrence matrix texture analyses. Structural knee abnormalities were graded using the whole-organ magnetic resonance imaging score (WORMS). We performed linear regression, adjusting for age, sex, body mass index, physical activity, smoking status, alcohol use, KL score, number of anti-hypertensive medications, and number of nonsteroidal anti-inflammatory drugs.ResultsHigher baseline DBP was associated with greater increases in global T2 (coefficient 0.22 (95% CI 0.09, 0.34), P = 0.004), global superficial layer T2 (coefficient 0.39 (95% CI 0.20, 0.58), P = 0.001), global contrast (coefficient 15.67 (95% CI 8.81, 22.53), P < 0.001), global entropy (coefficient 0.02 (95% CI 0.01, 0.03) P = 0.011), and global variance (coefficient 9.14 (95% CI 5.18, 13.09), P < 0.001). Compared with DBP, the associations of SBP with change in cartilage T2 parameters and WORMS subscores showed estimates of smaller magnitude.Conclusion
Higher baseline DBP was associated with higher and more heterogenous cartilage T2 values over 48 months, indicating increased cartilage matrix degenerative changes.
Background
Association between diabetes mellitus (DM) and risk of osteoarthritis (OA) can be confounded by body mass index (BMI), a strong risk factor for both conditions. We evaluate the association between DM or hyperglycaemia with OA using systematic review and meta-analysis.
Methods
We searched PubMed and Web of Science databases in English for studies that gave information on the association between DM and OA. Two meta-analysis models were conducted to address: (1) risk of DM comparing subjects with and without OA and (2) risk of OA comparing subjects with and without DM. As far as available, risk estimates that adjusted for BMI were used.
Results
31 studies with a pooled population size of 295 100 subjects were reviewed. 16 and 15 studies reported positive associations and null/ negative associations between DM and OA. 68.8% of positive studies had adjusted for BMI, compared with 93.3% of null/negative studies. In meta-analysis model 1, there was an increase prevalence of DM in subjects with OA compared with those without (OR 1.56, 95% CI 1.28 to 1.89). In meta-analysis model 2, there was no increased risk of OA (OR 1.14, 95% CI 0.98 to 1.33) in subjects with DM compared with those without, regardless of gender and OA sites. Comparing subjects with DM to those without, an increased risk of OA was noted in cross-sectional studies, but not in case-control and prospective cohort studies.
Conclusions
This meta-analysis does not support DM as an independent risk factor for OA. BMI was probably the most important confounding factor.
Résumé
L’association entre obésité et arthrose a un temps été considérée comme résultant uniquement d’une augmentation des charges mécaniques, mais il est probable que des facteurs systémiques interviennent également dans la physiopathologie de l’arthrose. L’excès de nutriments aboutissant à l’obésité peut provoquer une lipotoxicité qui pourrait être impliquée dans l’apparition de l’arthrose. Les différents types d’acides gras ont des effets distincts sur l’inflammation. Cette revue explore les études disponibles qui résument les effets des différents types d’acides gras sur l’arthrose et les tissus articulaires touchés. Des études chez l’animal ont montré que des acides gras poly-insaturés oméga 3 atténuaient l’expression des marqueurs de l’inflammation, de la dégradation du cartilage et du stress oxydatif dans les chondrocytes. À l’inverse, ces marqueurs ont augmenté sous la stimulation d’acides gras poly-insaturés oméga 6 et d’acides gras saturés. En outre, une diminution des douleurs et des troubles fonctionnels a été mise en évidence chez des chats et des chiens recevant une supplémentation en oméga 3. De la même manière, la plupart des études in vitro chez l’être humain révèlent une action pro-apoptotique et pro-inflammatoire des acides gras saturés. Tous les acides gras poly-instaurés ont réduit les marqueurs du stress oxydatif, et les oméga 3 ont également atténué la production de prostaglandine. Des études interventionnelles chez l’être humain utilisant une supplémentation en oméga 3 suggèrent un effet bénéfique sur la douleur et la capacité fonctionnelle, ainsi qu’une diminution des dommages structuraux. En revanche, un effet néfaste des acides gras saturés sur l’arthrose a été observé. Les études sur les acides gras mono-insaturés sont peu nombreuses et leurs résultats non concluants. Selon les études existantes, les acides gras poly-insaturés, et en particulier les oméga 3, ont un effet encourageant sur les signes et les symptômes de l’arthrose. D’autres études interventionnelles chez l’être humain sont toutefois nécessaires pour pouvoir tirer des conclusions solides.
Objective
Vascular pathology (changes in blood vessels) and osteoarthritis are both common chronic conditions associated with ageing and obesity, but whether vascular pathology is a risk factor for osteoarthritis is unclear. To systematically review the evidence for an association between vascular pathology and risk of joint specific osteoarthritis.
Methods
Scopus, Ovid Medline and EMBASE were searched between January 1946 and February 2019. MeSH terms and key words were used to identify studies examining the association between vascular pathology and osteoarthritis. Two reviewers independently extracted the data and assessed the methodological quality. Qualitative evidence synthesis was performed.
Results
Fifteen studies with high (n=3), fair (n=3) or low (n=9) quality were included. Features of vascular pathology included atherosclerosis, vascular stiffness, and endothelial dysfunction in different vascular beds. There was evidence for an association between vascular pathology and risk of hand osteoarthritis in women but not men, and between vascular pathology and risk of knee osteoarthritis in both men and women. Only two studies examined hip osteoarthritis showing no association between vascular pathology and risk of hip osteoarthritis.
Conclusion
There is evidence suggesting an association between vascular pathology and risk of hand and knee osteoarthritis with a potential causal relationship for knee osteoarthritis. Based on the limited evidence, it is hard to conclude an association for hip osteoarthritis. Further stronger evidence is needed to determine whether there is a causal relationship.
OBJECTIVE
To evaluate if type 2 diabetes is an independent risk predictor for severe osteoarthritis (OA).
RESEARCH DESIGN AND METHODS
Population-based cohort study with an age- and sex-stratified random sample of 927 men and women aged 40–80 years and followed over 20 years (1990–2010).
RESULTS
Rates of arthroplasty (95% CI) were 17.7 (9.4–30.2) per 1,000 person-years in patients with type 2 diabetes and 5.3 (4.1–6.6) per 1,000 person-years in those without (P < 0.001). Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard ratios (95% CI), 3.8 (2.1–6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1–3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA. The probability of arthroplasty increased with disease duration of type 2 diabetes and applied to men and women, as well as subgroups according to age and BMI. Our findings were corroborated in cross-sectional evaluation by more severe clinical symptoms of OA and structural joint changes in subjects with type 2 diabetes compared with those without type 2 diabetes.
CONCLUSIONS
Type 2 diabetes predicts the development of severe OA independent of age and BMI. Our findings strengthen the concept of a strong metabolic component in the pathogenesis of OA.
Background: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs).
Methods: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis.
Findings: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa.
Conclusions: Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world.
Funding: Bill & Melinda Gates Foundation.
Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs.
In total, 394 older men and women (mean age, 63 years; range, 52 to 79) were measured at baseline and approximately 2.7 years later. BMLs were determined by using T2-weighted fat-saturation magnetic resonance imaging (MRI) by measuring the maximal area of the lesion. Nutrient intake (total energy, fat, carbohydrate, protein, and sugar) and serum lipids were assessed at baseline.
Cross-sectionally, dietary factors and lipids were not significantly associated with BMLs. Energy, carbohydrate, and sugar intake (but not fat) were positively associated with a change in BML size (β = 15.44 to 19.27 mm2 per 1 SD increase; all P < 0.05). High-density lipoprotein (HDL) cholesterol tended to be negatively associated with BML change (β = -11.66 mm2 per 1 SD increase; P = 0.088).
Energy, carbohydrate, and sugar intake may be risk factors for BML development and progression. HDL cholesterol seems protective against BMLs. These results suggest that macronutrients and lipids may be important in BML etiology and that dietary modification may alter BML natural history.
Arthritis Research UK published a report in 2009 entitled "Osteoarthritis and obesity" in which they highlight the severe consequences of obesity for musculoskeletal health. Throughout the report, however, the mechanical effect of excess body weight is assumed to be the direct cause of osteoarthritis (OA). Although this assumption is common, is it supported by the evidence? A survey of the studies associating OA with obesity is inconclusive on whether body weight is the causative factor. The increase in direct-loading on joints due to weight-gain is not as great as is often believed, and compensatory gait patterns ameliorate much of the kinematic effects. One manifestation of obesity, however, is increased adipose tissue--a rich source of proinflammatory endocrine factors. I propose that body weight might not be the main problem in OA pathogenesis, but that increased adipose tissue itself might be both an indicator and a driver of widespread disease.
Given the emerging evidence that osteoarthritis (OA) may have a vascular basis, the aim of this study was to determine whether serum lipids were associated with change in knee cartilage, presence of bone marrow lesions (BMLs) at baseline and the development of new BMLs over a 2-year period in a population of pain-free women in mid-life.
One hundred forty-eight women 40 to 67 years old underwent magnetic resonance imaging (MRI) of their dominant knee at baseline and 2.2 (standard deviation 0.12) years later. Cartilage volume and BMLs were determined for both time points. Serum lipids were measured from a single-morning fasting blood test approximately 1.5 years prior to the MRI.
The incidence of BML at follow-up was associated with higher levels of total cholesterol (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.01, 3.36; P = 0.048) and triglycerides (OR 8.4, 95% CI 1.63, 43.43; P = 0.01), but not high-density lipoprotein (HDL) (P = 0.93), low-density lipoprotein (LDL) (P = 0.20) or total cholesterol/HDL ratio (P = 0.17). No association between total cholesterol, triglycerides, HDL, LDL or total cholesterol/HDL ratio and presence of BMLs at baseline or annual change in total tibial cartilage volume was observed.
In this study of asymptomatic middle-aged women with no clinical knee OA, serum cholesterol and triglyceride levels were associated with the incidence of BMLs over 2 years. This provides support for the hypothesis that vascular pathology may have a role in the pathogenesis of knee OA. Further work is warranted to clarify this and whether treatments aimed at reducing serum lipids may have a role in reducing the burden of knee OA.
Osteoarthritis (OA) and cardiovascular disease (CVD) share age and obesity as risk factors, but may also be linked by pathogenic mechanisms involving metabolic abnormalities and systemic inflammation. This study compared the prevalence of OA and metabolic syndrome (MetS) in subjects with OA versus the general population without OA to determine whether having OA predicts increased cardiovascular risk.
National Health and Nutrition Examination Survey III data were used as a representative sample of the general US population. Subjects included adults aged > or = 18 years with records of history, physical, radiographic, and laboratory data adequate to assess for diagnoses of MetS and OA. Logistic regression was used to examine the association between MetS and population-weighted variables.
The general population sample included 7714 subjects (weighted value representing 174.9 million population), of whom 975 subjects had OA (weighted value 17.5 million) and 6739 did not (weighted value 157.4 million). Metabolic syndrome was prevalent in 59% of the OA population and 23% of the population without OA. Each of the 5 cardiovascular risk factors that comprise MetS was more prevalent in the OA population versus the population without OA: hypertension (75% vs 38%), abdominal obesity (63% vs 38%), hyperglycemia (30% vs 13%), elevated triglycerides (47% vs 32%), and low high-density lipoprotein cholesterol (44% vs 38%). Metabolic syndrome was more prevalent in subjects with OA regardless of sex or race. The association between OA and MetS was greater in younger subjects and diminished with increasing age. Having OA at age 43.8 years (mean age of the general population) was associated with a 5.26-fold (SE = 1.58, P < 0.001) increased risk of MetS. This association remained strong when obesity was controlled for in additional regression models.
Osteoarthritis is associated with an increased prevalence of MetS, particularly in younger individuals. Global cardiovascular risk should be assessed in individuals aged < or = 65 years with OA, and should be considered when prescribing analgesics for OA patients.
Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. It is unknown whether the adipose mass and the distribution of adipose mass are associated with the risk of primary knee and hip replacement for osteoarthritis. The aim of the present investigation was to examine this in a cohort study.
A total of 39,023 healthy volunteers from Melbourne, Australia were recruited for a prospective cohort study during 1990 to 1994. Their body mass index, waist circumference, and waist-to-hip ratio were obtained from direct anthropometric measurements. The fat mass and percentage fat were estimated from bioelectrical impedance analysis. Primary knee and hip replacements for osteoarthritis between 1 January 2001 and 31 December 2005 were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) for primary joint replacement associated with each adiposity measure.
Comparing the fourth quartile with the first, there was a threefold to fourfold increased risk of primary joint replacement associated with body weight (HR = 3.44, 95% confidence interval (CI) = 2.83 to 4.18), body mass index (HR = 3.44, 95% CI = 2.80 to 4.22), fat mass (HR = 3.51, 95% CI = 2.87 to 4.30), and percentage fat (HR = 2.99, 95% CI = 2.46 to 3.63). The waist circumference (HR = 2.77, 95% CI = 2.26 to 3.39) and waist-to-hip ratio (HR = 1.46, 95% CI = 1.21 to 1.76) were less strongly associated with the risk. Except for the waist-to-hip ratio, which was not significantly associated with hip replacement risk, all adiposity measures were associated with the risk of both knee and hip joint replacement, and were significantly stronger risk factors for knee.
Risk of primary knee and hip joint replacement for osteoarthritis relates to both adipose mass and central adiposity. This relationship suggests both biomechanical and metabolic mechanisms associated with adiposity contribute to the risk of joint replacement, with stronger evidence at the knee rather than the hip.
In the financial year ending June 2002, 26 689 hip replacements and 26089 knee replacements (total, 52778) were performed in Australia. Hip and knee replacement procedures have increased between 5%-10% each year for the past 10 years, with a combined increase in hip and knee replacement of 13.4% in the past year. The revision rate for hip replacement surgery in Australia is unknown but is estimated to be 20%-24%; the revision rate for hip replacement surgery in Sweden is 7%. Although data collection for the Registry is voluntary, it has 100% compliance from hospitals undertaking joint-replacement surgery.
White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.
Growing evidence from epidemiological studies suggests that osteoarthritis (OA) is linked to atheromatous vascular disease. This hypothesis article proposes that OA, or at least OA structural progression, may be an atheromatous vascular disease of subchondral bone. Further epidemiological studies, imaging investigations of relevant blood vessels, and trials of the effects of statins on the prevention and treatment of OA are needed to examine this hypothesis.
Osteoarthritis is usually considered to be a joint disorder the central pathological feature of which is cartilage destruction. However, this concept has evolved, and today osteoarthritis is generally regarded as a disease that may affect the whole joint (bone, muscles, ligaments and synovium). Although the aetiology of osteoarthritis is not established, the main risk factors are well known and commonly include mechanical, biochemical and genetic factors. Of these risk factors, obesity is beyond doubt considered a prominent one.
The authors used data from the United States first national Health and Nutrition Examination Survey of 1971–1975 (HANES I) to explore the cross-sectional associations between radiographic osteoarthritis of the knee and a variety of putative risk factors. A total of 5,193 black and white study participants aged 35– 74 years, 315 of whom had x-ray-diagnosed osteoarthritis of the knee, were available for analysis. After controlling for confounders, the authors found significant associations of knee osteoarthritis with overweight, race, and occupation, all of which have been suggested by smaller cross-sectional studies. They then focused specifically on those factors. For overweight, they found a strong association between current obesity and osteoarthritis of the knee, with a dose-response effect not previously assessed. This association was also seen for self-reported minimum adult weight, a proxy for long-term obesity, and was present in persons with asymptomatic osteoarthritis of the knee. These findings strongly suggest that obesity is causative. HANES I was the first study in which racial differences in osteoarthritis of the knee could be assessed within the same country. The black women who were studied had an increased risk of disease (odds ratio (OR) = 2.12, 95% confidence interval (Cl) = 1.39−3.23) after controlling for age and weight, although the black men did not. Finally, the authors used the US Department of Labor Dictionary of Occupational Titles to obtain characterizations of the physical demands and knee-bending stress associated with occupations and to study the relation between physical demands of jobs and osteoarthritis of the knee. They found for persons aged 55–64 years an association between knee-bending demands and osteoarthritis of the knee (men, OR = 2.45, 95% CI = 1.21−4.97; women, OR = 3.49, 95% CI = 1.22−10.52). Since such occupational physical demands are common, the authors conclude that they may be associated with a substantial proportion of osteoarthritis of the knee.
In the financial year ending June 2002, 26 689 hip replacements and 26 089 knee replacements (total, 52 778) were performed in Australia. Hip and knee replacement procedures have increased between 5%-10% each year for the past 10 years, with a combined increase in hip and knee replacement of 13.4% in the past year. The revision rate for hip replacement surgery in Australia is unknown but is estimated to be 20%-24%; the revision rate for hip replacement surgery in Sweden is 7%. Although data collection for the Registry is voluntary, it has 100% compliance from hospitals undertaking joint-replacement surgery
Objective: This study examined whether vascular alterations are associated with the presence and progression of osteoarthritis of the knee, the hip and the different hand joints in a large prospective cohort study. Methods: In this population-based study involving participants aged 55 years and older (Rotterdam Study I), men (n=2372) and women (n=3278) were analysed separately. x-Rays of the knee, hip and hand were scored using the Kellgren and Lawrence score for osteoarthritis at baseline, after 6.6 years and 10 years. Measures of atherosclerosis (carotid intima media thickness (IMT) and carotid plaque) and data on covariates (age, body mass index, hypertension, cholesterol ratio, diabetes mellitus and smoking) were collected at baseline. Multivariate logistic regression models with generalised estimated equations were used to calculate OR and corresponding 95% CI. Secondary multiple comparison adjustment resulted in a significance level of p<0.0021. Results: In women, IMT showed an independent association with the prevalence of knee osteoarthritis (adjusted OR (aOR) 1.7, 1.1 to 2.7), and carotid plaque with distal interphalangeal (DIP) osteoarthritis (aOR 1.4, 1.2 to 1.7) and with metacarpophalangeal osteoarthritis (aOR 1.5, 1.1 to 2.2). An independent association for IMT with progression of metacarpophalangeal osteoarthritis was found in women (aOR 2.9, 1.18 to 6.93). Additional adjustment for multiple testing yielded a significant association between carotid plaque and DIP osteoarthritis in women (p<0.001). Conclusions: This study showed independent associations of atherosclerosis with osteoarthritis of the knee and hand joints in women. The evidence was most solid for a relation with DIP osteoarthritis. More research is needed to confirm the associations and examine the differential association with various joints.
Results: Participants born in Italy and Greece had a lower rate of primary joint replacement compared with those born in Australia [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26−0.39, P < 0.001], independent of age, gender, body mass index, education level, and physical functioning. This lower rate was observed for joint replacements performed in private hospitals (HR 0.17, 95% CI 0.13−0.23), but not for joint replacements performed in public hospitals (HR 0.96, 95% CI 0.72−1.29). Conclusions: People born in Italy and Greece had a lower rate of primary joint replacement for osteoarthritis in this cohort study, compared to Australian-born people, which could not simply be explained by factors such as education level and physical functioning, despite being overweight. This may be due to poorer access to health care or social factors and preferences regarding treatment. However, it may reflect ethnic differences in rates of progression to end stage osteoarthritis. Understanding this warrants further investigation.
Imhof H, Sulzbacher I, Grampp S, Czerny C, Youssefzadeh S, Kainberger F. Subchondral bone and cartilage disease: A rediscovered functional unit. Invest Radiol 2000;35:581-588.
ABSTRACT. The role of subchondral bone in the pathogenesis of cartilage damage has likely been underestimated. Subchondral bone is not only an important shock absorber, but it may also be important for cartilage metabolism. Contrary to many drawings and published reports, the subchondral region is highly vascularized and vulnerable. Its terminal vessels have, in part, direct contact with the deepest hyaline cartilage layer. The perfusion of these vessels accounts for more than 50% of the glucose, oxygen, and water requirements of cartilage. Bony structure, local metabolism, hemodynamics, and vascularization of the subchondral region differ within a single joint and from one joint to another. Owing to these differences, repetitive, chronic overloading or perfusion abnormalities may result in no pathological reaction at all in one joint, while in another joint, these same conditions may lead to osteonecrosis, osteochondritis dissecans, or degenerative changes. According to this common etiological root, similar pathological reactions beginning with marrow edema and necrosis and followed by bone and cartilage fractures, joint deformity, and insufficient healing processes are found in osteonecrosis, osteochondritis dissecans, and degenerative disease as well.
Metabolic osteoarthritis (OA) has now been characterized as a subtype of OA, and links have been discovered between this phenotype and metabolic syndrome (MetS)-both with individual MetS components and with MetS as a whole. Hypertension associates with OA through subchondral ischaemia, which can compromise nutrient exchange into articular cartilage and trigger bone remodelling. Ectopic lipid deposition in chondrocytes induced by dyslipidemia might initiate OA development, exacerbated by deregulated cellular lipid metabolism in joint tissues. Hyperglycaemia and OA interact at both local and systemic levels; local effects of oxidative stress and advanced glycation end-products are implicated in cartilage damage, whereas low-grade systemic inflammation results from glucose accumulation and contributes to a toxic internal environment that can exacerbate OA. Obesity-related metabolic factors, particularly altered levels of adipokines, contribute to OA development by inducing the expression of proinflammatory factors as well as degradative enzymes, leading to the inhibition of cartilage matrix synthesis and stimulation of subchondral bone remodelling. In this Review, we summarize the shared mechanisms of inflammation, oxidative stress, common metabolites and endothelial dysfunction that characterize the aetiologies of OA and MetS, and nominate metabolic OA as the fifth component of MetS. We also describe therapeutic opportunities that might arise from uniting these concepts.
To clarify the association between the occurrence and progression of knee osteoarthritis (KOA) with components of metabolic syndrome (MS), including overweight (OW), hypertension (HT), dyslipidaemia (DL), and impaired glucose tolerance (IGT), in a general population.
From the large-scale population-based cohort study entitled Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) initiated in 2005, 1,690 participants (596 men, 1,094 women) residing in mountainous and coastal areas were enrolled. Of these, 1,384 individuals (81.9%; 466 men, 918 women) completed the second survey, including knee radiography, 3 years later. KOA was defined as Kellgren-Lawrence (KL) grade ≥ 2 using paired X-ray films. Based on changes in KL grades between the baseline and second surveys, cumulative incidence and progression of KOA were determined. OW, HT, DL, and IGT at baseline were assessed using standard criteria.
The cumulative incidence of KOA among 1,384 completers over 3 years was 3.3%/year, and progression in KL grades for either knee, 8.0%/year. Logistic regression analyses after adjusting for potential risk factors revealed that the odds ratio (OR) for the occurrence of KOA significantly increased according to the number of MS components present (OR vs no component: one component, 2.33; two components, 2.82; ≥three components, 9.83). Similarly, progression of KOA significantly increased according to the number of MS components present (OR vs no component: one component, 1.38; two components, 2.29; ≥three components: 2.80).
Accumulation of MS components is significantly related to both occurrence and progression of KOA. MS prevention may be useful in reducing future KOA risk.
There is evidence to suggest that elevated glucose concentration and clinical diabetes are associated with osteoarthritis (OA). However, the association may be confounded by knee symptoms, concomitant treatment for OA or diabetes. We performed a longitudinal cohort study to examine the relationship between serum glucose concentration and knee structure in adults with no knee symptoms or diabetes.
179 participants who had fasting serum glucose measurements at 1990-4, with no knee symptoms or diabetes (physician-diagnosed or fasting serum glucose ≥7 mmol/L), underwent knee MRI in 2003-4 and 2 years later. Body mass index was measured at 1990-4 and 2003-4. Cartilage volume and bone marrow lesions were determined from MRI at 2003-4 and 2006-7.
Fasting serum glucose concentration was positively associated with the rate of tibial cartilage volume loss over 2 years in women (B=44.2mm(3), 95% CI 4.6, 83.8) but not in men (B=6.0mm(3), 95% CI -68.5, 80.6). Fasting serum glucose concentration was positively associated with incident bone marrow lesions in women (OR=5.76, 95% CI 1.06, 31.21) but not in men (OR=0.11, 95% CI 0.01, 1.79) with significant gender difference (p=0.001 for interaction).
Increased fasting serum glucose concentration in a non-diabetic population was associated with adverse structural changes at the knee in women but not in men, suggesting that there may be susceptibility to knee structural change even below the arbitrary "diabetic range" of serum glucose levels. The sex differences warrant further investigation as this may be one mechanism underlying the sex difference in knee OA.
Objective This study examined whether vascular alterations are associated with the presence and progression of osteoarthritis of the knee, the hip and the different hand joints in a large prospective cohort study.
Methods In this population-based study involving participants aged 55 years and older (Rotterdam Study I), men (n=2372) and women (n=3278) were analysed separately. x-Rays of the knee, hip and hand were scored using the Kellgren and Lawrence score for osteoarthritis at baseline, after 6.6 years and 10 years. Measures of atherosclerosis (carotid intima media thickness (IMT) and carotid plaque) and data on covariates (age, body mass index, hypertension, cholesterol ratio, diabetes mellitus and smoking) were collected at baseline. Multivariate logistic regression models with generalised estimated equations were used to calculate OR and corresponding 95% CI. Secondary multiple comparison adjustment resulted in a significance level of p<0.0021.
Results In women, IMT showed an independent association with the prevalence of knee osteoarthritis (adjusted OR (aOR) 1.7, 1.1 to 2.7), and carotid plaque with distal interphalangeal (DIP) osteoarthritis (aOR 1.4, 1.2 to 1.7) and with metacarpophalangeal osteoarthritis (aOR 1.5, 1.1 to 2.2). An independent association for IMT with progression of metacarpophalangeal osteoarthritis was found in women (aOR 2.9, 1.18 to 6.93). Additional adjustment for multiple testing yielded a significant association between carotid plaque and DIP osteoarthritis in women (p<0.001).
Conclusions This study showed independent associations of atherosclerosis with osteoarthritis of the knee and hand joints in women. The evidence was most solid for a relation with DIP osteoarthritis. More research is needed to confirm the associations and examine the differential association with various joints.
To examine the relationship of knee osteoarthritis (OA) with cardiovascular and metabolic risk factors by obesity status and gender.
Data from 1,066 National Health and Nutrition Examination Survey III participants (≥60 years of age) was used to examine relationships of osteophytes-defined radiographic knee OA and cardiovascular and metabolic measures. Analyses were considered among obese [body mass index (BMI)≥30 kg/m(2)] and non-obese (BMI<30 kg/m(2)) men and women.
The prevalence of osteophytes-defined radiographic knee OA was 34%. Leptin levels and homeostatic model assessment-insulin resistance (HOMA-IR), a proxy measure of insulin resistance, were significantly associated with knee OA; those with knee OA had 35% higher HOMA-IR values and 52% higher leptin levels compared to those without knee OA. The magnitude of the association between HOMA-IR and knee OA was strongest among men, regardless of obesity status; odds ratios (ORs) for HOMA-IR were 34% greater among non-obese men (OR=1.18) vs obese women (OR=0.88). Among obese women, a 5-μg/L higher leptin was associated with nearly 30% higher odds of having knee OA (OR=1.28). Among men, ORs for the association of leptin and knee OA were in the opposite direction.
Cardiometabolic dysfunction is related to osteophytes-defined radiographic knee OA prevalence and persists within subgroups defined by obesity status and gender. A sex dimorphism in the direction and magnitude of cardiometabolic risk factors with respect to knee OA was described including HOMA-IR being associated with OA prevalence among men while leptin levels were most important among women.
The objectives of this study were to investigate the prevalence rate of metabolic syndrome (MetS) among knee osteoarthritis (OA) patients in the Japanese general population, and to analyze the relationship between MetS and knee OA.
A total of 795 volunteers participated in this study. Based on the Kellgren-Lawrence (K-L) grade, participants were classified into two groups: the non-knee OA (non-KOA) group (K-L grade 0 or 1) or knee OA (KOA) group (grade 2-4). MetS was defined according to the Japanese Committee for the Diagnostic Criteria of MetS with a slight modification. The presence of hyperlipidemia, hypertension, diabetes mellitus and MetS were compared between the non-KOA and KOA groups. Furthermore, risk factors for MetS were analyzed by logistic regression analysis.
The prevalence rate of hypertension in the KOA group was significantly higher than in the non-KOA group (P = 0.025) in males. Those of hypertension (P < 0.001), hyperlipidemia (P < 0.001) and diabetes mellitus (P = 0.019) in the KOA group were significantly higher than in the non-KOA group in females. Aging was significantly associated with MetS in males; the odds ratio (OR) for age was 1.033 (P = 0.020), suggesting that a 1-year increase in age raised the risk of MetS. In females, the presence of KOA was significantly associated with MetS; the risk of MetS in the KOA group was 2.196 (P = 0.034) fold the risk in the non-KOA group.
The prevalence rates of MetS and knee OA tended to increase with age in males; however, there was no association between MetS and knee OA. On the other hand, knee OA was significantly associated with MetS in females. Knee OA patients must be provided the best treatment approach because of their high risk for MetS, which promotes cardiovascular diseases.
To clarify the association of knee osteoarthritis (KOA) with overweight (OW), hypertension (HTN), dyslipidemia (DL), and impaired glucose tolerance (IGT), which are components of metabolic syndrome (MS), in a Japanese population.
We enrolled 1690 participants (596 men, 1094 women) from the large-scale cohort study Research on Osteoarthritis Against Disability (ROAD), begun in 2005 to clarify epidemiologic features of OA in Japan. KOA was evaluated by the Kellgren-Lawrence grade, minimum joint space width (MJSW), minimum joint space area (JSA), and osteophyte area (OPA). OW, HTN, DL, and IGT were assessed using standard criteria.
The prevalence of KOA in the total population in the age groups ≤ 39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years was 2.2%, 10.7%, 28.2%, 50.8%, 69.0%, and 80.5%, respectively. Logistic regression analyses after adjustment for age, sex, regional difference, smoking habit, alcohol consumption, physical activities, regular exercise, and history of knee injuries revealed that the OR of KOA significantly increased according to the number of MS components present (1 component: OR 1.21, 95% CI 0.88-1.68, p = 0.237; 2 components: OR 1.89, 95% CI 1.33-2.70, p < 0.001; 3 or more components: OR 2.72, 95% CI 1.77-4.18; p < 0.001). The number of MS components was inversely related to medial MSJW (ß = -0.148, R(2) = 0.21, p < 0.001), medial JSA (women only; ß = -0.096, R(2) = 0.18, p = 0.001), and positively related to OPA (ß = 0.12, R(2) = 0.11, p < 0.001).
The accumulation of MS components is significantly related to presence of KOA. MS prevention may be useful to reduce cardiovascular disease and KOA risk.
Osteoarthritis (OA) is an age-related degenerative disease comprising the main reason of handicap in the Western world. Interestingly, to date, there are neither available biomarkers for early diagnosis of the disease nor any effective therapy other than symptomatic treatment and joint replacement surgery. OA has long been associated with obesity, mainly due to mechanical overload exerted on the joints. Recent studies however, point to the direction that OA is a metabolic disease, as it also involves non-weight bearing joints. In fact, altered lipid metabolism may be the underlying cause. First, adipokines have been shown to be key regulators of OA pathogenesis. Second, epidemiological studies have shown serum cholesterol to be a risk factor for OA development. Third, lipid deposition in the joint is observed at the early stages of OA before the occurrence of histological changes. Fourth, proteomic analyses have shown an important connection between OA and lipid metabolism. Finally, recent gene expression studies reveal a deregulation of cholesterol influx and efflux and in the expression of lipid metabolism-related genes. Interestingly, lipids and lipid metabolism are known to be implicated in the development and progression of another age-related degenerative disease, atherosclerosis (ATH). Thus, although it is tempting to speculate that the osteoarthritic chondrocyte has been transformed to foam cell, it has not been proven yet. However, this may be an intriguing theory linking ATH and OA, which may open new avenues to novel therapeutic interventions for OA taking advantage of previous knowledge from ATH.
Hyperlipidemia is a major risk factor for coronary heart disease. The most commonly used antihyperlipidemic drugs are 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), of which atorvastatin is one of the most widely used. Little is known about the relationship between tendinopathy and HMG CoA reductase inhibitors (statins) or the effects of atorvastatin use on tendon healing following surgical repair of tendon rupture. We hypothesized that atorvastatin negatively affects this healing process.
The Achilles tendons of 16 New Zealand rabbits were ruptured surgically and repaired with sutures. Eight of the rabbits were given oral atorvastatin. The other 8 served as a surgical control group. Six weeks postoperatively, all the rabbits were sacrificed, and the repaired tendons were removed. After standard histological preparation, fibroblastic activity, revascularization, collagenization, collagen construction, and inflammatory-cell infiltration were evaluated. On comparing the atorvastatin and surgical control groups, we observed no difference in fibroblastic activity. Although it did not reach statistical significance in our study, a difference was noted in revascularization, collagenization, and inflammatory cell infiltration; and a statistical difference was observed in collagen construction.
Doubt remains about the adverse effect of atorvastatin use during tendon healing. Further investigations in animal and human models are needed on the effects of tendon healing when atorvastatin is administered for a longer time frame prior to the injury.
The frequency of knee osteoarthritis continues to accelerate, likely because of the increasing proliferation of obesity, particularly in men and women 40-60 years of age at the leading edge of the 'baby boom' demographic expansion. The increasing pervasiveness of obesity and the growing appreciation of obesity's accompanying metabolic/inflammatory activities suggest rethinking the knee osteoarthritis paradigm.
Whereas once knee osteoarthritis was considered a 'wear-and-tear' condition, it is now recognized that knee osteoarthritis exists in the highly metabolic and inflammatory environments of adiposity. Cytokines associated with adipose tissue, including leptin, adiponectin, and resistin, may influence osteoarthritis though direct joint degradation or control of local inflammatory processes. Further, pound-for-pound, not all obesity is equivalent for the development of knee osteoarthritis; development appears to be strongly related to the co-existence of disordered glucose and lipid metabolism. Additionally, obesity loads may be detected by mechanoreceptors on chondrocyte surfaces triggering intracellular signaling cascades of cytokines, growth factors, and metalloproteinases.
This review summarizes recent literature about obesity, knee osteoarthritis and joint pain. Consideration of adipocytokines, metabolic factors, and mechanical loading-metabolic factor interactions will help to broaden the thinking about targets for both prevention and intervention for knee osteoarthritis.
Osteoarthritis (OA) has become a major public health problem not only because of its increasing prevalence worldwide but also because of its frequent association with cardiovascular disease, the leading cause of death in industrialized countries. There is growing evidence that OA is not simply a disease related to aging or mechanical stress of joints but rather a "metabolic disorder" in which various interrelated lipid, metabolic, and humoral mediators contribute to the initiation and progression of the disease process. Indeed, OA has been linked not only to obesity but also to other cardiovascular risk factors, namely, diabetes, dyslipidemia, hypertension, and insulin resistance.
It is estimated that Asia will be the home of more than 100 million people with type 2 diabetes by the year of 2025. This region combines a high proportion of the world's population with rapidly rising diabetes prevalence rates. The increase in diabetes in Asia differs from that reported in other parts of the world: it has developed in a shorter time, in a younger age group, and in people with lower body-mass index (BMI). Studies reported that for the same BMI, Asians have a higher body fat percentage, a prominent abdominal obesity, a higher intramyocellular lipid and/or a higher liver fat content compared to Caucasians. These characteristics may contribute to a higher predisposition to insulin resistance at a lesser degree of obesity than Caucasians. The differences in body composition are more pronounced depending on the region. For the same BMI, among three major ethnic groups in Asia, Asian Indians have the highest body fat, followed by Malay and Chinese. Lower insulin sensitivity is already observed in Asian Indian adolescents with a higher body fat and abdominal obesity compared to Caucasian adolescents. In general, Asian adolescents share the same feature of body composition such as higher body subcutaneous fat, lower appendicular skeletal muscle and lower gynoid fat compared to Caucasian adolescents. This unfavourable body composition may predispose to the development of insulin resistance at later age. Genetics may play a role and the interaction with environmental factors (changes in lifestyle) could increase the risk of developing the metabolic syndrome.
To assess the role of obesity and metabolic dysfunctionality with knee osteoarthritis (OA), knee joint pain, and physical functioning performance, adjusted for joint space width (JSW) asymmetry.
Knee OA was defined as a Kellgren/Lawrence score > or =2 on weight-bearing radiographs. Obesity was defined as a body mass index > or =30 kg/m2. Cardiometabolic clustering classification was based on having > or =2 of the following factors: low levels of high-density lipoprotein cholesterol; elevated levels of low-density lipoprotein cholesterol, triglycerides, blood pressure, C-reactive protein, waist:hip ratio, or glucose; or diabetes mellitus. The difference between lateral and medial knee JSW was used to determine joint space asymmetry.
In a sample of women (n = 482, mean age 47 years), prevalences of knee OA and persistent knee pain were 11% and 30%, respectively. The knee OA prevalence in nonobese women without cardiometabolic clustering was 4.7%, compared with 12.8% in obese women without cardiometabolic clustering and 23.2% in obese women with cardiometabolic clustering. Nonobese women without cardiometabolic clustering were less likely to perceive themselves as limited compared with women in all other obesity/cardiometabolic groups (P < 0.05). Similar associations were seen with knee pain and physical functioning measures. The inclusion of a joint space asymmetry measure was associated with knee OA but not with knee pain or physical functioning.
Knee OA was twice as frequent in obese women with cardiometabolic clustering compared with those without, even when considering age and joint asymmetry. Obesity/cardiometabolic clustering was also associated with persistent knee pain and impaired physical functioning.
Tendon injuries have been reported to occur more frequently in individuals with increased adiposity. Treatment also appears to have poorer outcomes among these individuals. Our objective was to examine the extent and consistency of associations between adiposity and tendinopathy.
A systematic review of observational studies was conducted. Eight electronic databases were searched (Allied and Complementary Medicine, Biological Abstracts, CINAHL, Current Contents, EMBase, Medline, SPORTDiscus, and Web of Science) and citation tracking was performed on included reports. Studies were included if they compared adiposity between subjects with and without tendon injury or examined adiposity as a predictor of conservative treatment success.
Four longitudinal cohorts, 14 cross-sectional studies, 8 case-control studies, and 2 interventional studies (28 in total) met the inclusion criteria, providing a total of 19,949 individuals. Forty-two subpopulations were identified, 18 of which showed elevated adiposity to be associated with tendon injury (43%). Sensitivity analyses indicated a clustering of positive findings among studies that included clinical patients (81% positive) and among case-control studies (77% positive).
Elevated adiposity is frequently associated with tendon injury. Published reports suggest that elevated adiposity is a risk factor for tendon injury, although this association appears to vary depending on aspects of study design and measurement. Adiposity is of particular interest in tendon research because, unlike a number of other reported risk factors for tendon injury, it is somewhat preventable and modifiable. Further research is required to determine if reducing adiposity will reduce the risk of tendon injury or improve the results of treatment.
To determine whether nuclear magnetic resonance (NMR)-determined lipoprotein profiles predict type 2 diabetes.
Subjects were 813 male and female participants in the Melbourne Collaborative Cohort Study, aged 40-69 years at baseline (1990-1994), and with a baseline fasting plasma glucose <7.0 mmol/L. Incident type 2 diabetes was identified in 1994-1998 by self-report and confirmation from doctors. Eligible cases and a random group of controls were selected, with NMR data available for 59 cases and 754 non-cases.
Concentration of very low density lipoprotein (VLDL) particles (positive) and high density lipoprotein (HDL) particle size (negative) were selected by stepwise regression as predictors of type 2 diabetes. These associations were independent of other non-lipid risk factors, but not plasma triglycerides. Factor analysis identified a factor from NMR variables, explaining 47% of their variation, and characterized by a positive correlation with VLDL, particularly large and medium sized; more low density lipoprotein (LDL) that were smaller; and relatively smaller, but not more HDL particles. This factor was positively associated with diabetes incidence, but not independently of triglycerides.
We identified an atherogenic NMR lipoprotein profile in people who developed diabetes, but this did not improve diabetes prediction beyond conventional triglyceride levels.
To explore the relationships between C-reactive protein (CRP), metabolic syndrome (MetS) and incidence of severe knee or hip osteoarthritis (OA) in a prospective study.
A population-based cohort (n=5171, mean age 57.5+/-5.9 years) was examined between 1991 and 1994. Data was collected on lifestyle habits, measures of overweight, blood pressure as well as high-density lipoprotein (HDL) cholesterol, triglycerides, glucose and CRP measured with high-sensitive methods. Incidence of severe OA, defined as arthroplasty due to knee or hip OA, was monitored over 12 years of follow-up, in relation to CRP levels and presence of the MetS according to the adult treatment panel III-national cholesterol education program (ATPIII-NCEP) definition.
A total of 120 participants had severe hip OA and 89 had knee OA during the follow-up. After adjustment for age, sex, smoking, physical activity and CRP, presence of MetS was associated with significantly increased risk of knee OA (relative risk [RR]: 2.1, 95% confidence interval [CI]: 1.3-3.3). However, this relationship was attenuated and non-significant after adjustment for body mass index (BMI) (RR: 1.1, 95% CI: 0.7-1.8). MetS was not significantly associated with incidence of hip OA. In women, CRP was associated with knee OA in the age-adjusted analysis. However, there was no significant relationship between CRP and incidence of knee or hip OA after risk factor adjustments.
The increased incidence of knee OA in participants with the MetS was largely explained by increased BMI. CRP was not associated with incidence of knee or hip OA when possible confounding factors were taken into account.
The clinical, pathological, and epidemiological relationships between fasting plasma glucose (FPG) concentrations and the sites of lesion in osteoarthritis (OA) were evaluated in 1026 patients. The mean FPG (99 +/- 22.2 mg/dL) was significantly higher in OA (p less than 0.01) than in the normal controls (88 +/- 19.9 mg/dL). In addition, the mean FPG (97.9 +/- 23 mg/dL) was significantly higher in female patients with OA (p less than 0.01) than in an osteoporotic sex-matched control group (92.8 +/- 24.5). FPG concentrations did not vary significantly according to the sites of the OA lesions. Fifty-six (5.5%) OA patients had long-term diabetes mellitus (FPG greater than 140 mg/dl). Few significant differences in the pathological and clinical findings were seen between normoglycemic and hyperglycemic OA patients, only the ESR (p less than 0.01) and pain at rest (p less than 0.02) being higher in the second group. These epidemiological data support the observation that hyperglycemia, which acts on matrix macromolecules, may be related to the development of bone degenerative disease.
This review has focused on the prevalence and risk factors associated with knee and hip osteoarthritis. Risk factors for knee osteoarthritis are obesity and major injury, and knee osteoarthritis probably fits into the generalized osteoarthritis diathesis. Repetitive use, such as in jobs requiring heavy labor and knee bending, probably increases the risk of knee osteoarthritis. Hip osteoarthritis is probably frequently secondary to developmental defects. As Rothman (182) has pointed out in discussing causation, this does not necessarily mean that the same factors do not also contribute to causing hip osteoarthritis. Yet, it appears that, in many cases, developmental defects are severe enough to be sufficient causes of hip osteoarthritis. To delineate other causes, it may be necessary to examine risk factors separately in those with and in those without developmental disease. Although large epidemiologic studies are best able to identify the relative contributions of specific risk factors while controlling for other risk factors, new studies need to focus on important unresolved questions. First, longitudinal studies with comprehensive follow-up using repeated radiographic assessments are needed to identify factors that cause development of disease or the onset of symptoms. Second, cohorts with early and possibly asymptomatic disease need to be followed to determine the causes of progression or regression of disease and the natural history of disease. Such cohorts may include those at high risk of injury such as sports enthusiasts or manual laborers.
The authors used data from the United States first national Health and Nutrition Examination Survey of 1971-1975 (HANES I) to explore the cross-sectional associations between radiographic osteoarthritis of the knee and a variety of putative risk factors. A total of 5,193 black and white study participants aged 35-74 years, 315 of whom had x-ray-diagnosed osteoarthritis of the knee, were available for analysis. After controlling for confounders, the authors found significant associations of knee osteoarthritis with overweight, race, and occupation, all of which have been suggested by smaller cross-sectional studies. They then focused specifically on those factors. For overweight, they found a strong association between current obesity and osteoarthritis of the knee, with a dose-response effect not previously assessed. This association was also seen for self-reported minimum adult weight, a proxy for long-term obesity, and was present in persons with asymptomatic osteoarthritis of the knee. These findings strongly suggest that obesity is causative. HANES I was the first study in which racial differences in osteoarthritis of the knee could be assessed within the same country. The black women who were studied had an increased risk of disease (odds ratio (OR) = 2.12, 95% confidence interval (CI) = 1.39-3.23) after controlling for age and weight, although the black men did not. Finally, the authors used the US Department of Labor Dictionary of Occupational Titles to obtain characterizations of the physical demands and knee-bending stress associated with occupations and to study the relation between physical demands of jobs and osteoarthritis of the knee. They found for persons aged 55-64 years an association between knee-bending demands and osteoarthritis of the knee (men, OR = 2.45, 95% CI = 1.21-4.97; women, OR = 3.49, 95% CI = 1.22-10.52). Since such occupational physical demands are common, the authors conclude that they may be associated with a substantial proportion of osteoarthritis of the knee.
Several studies have shown an association with density and knee osteoarthritis (OA), however the role of other metabolic factors is unclear, with conflicting data in the literature. We studied the association between metabolic risk factors and k nee OA in women in the general population.
One thousand three women aged 45-64 from the Chingford population study completed risk factor questionnaires. Current blood pressure and ever hypertension were noted and fasting blood glucose, serum cholesterol, triglycerides, high density lipoprotein( HDL), and uric acid levels were measured. AP weight bearing radiographs were available in 979 women and scored using the Kellgren and Lawrence system. Grade 2+ (definite osteophytes) was used a definition of knee OA. Odds ratios (OR) and 95% confidence intervals were calculated for risk of knee OA in highest tertile versus lowest for death risk factor. All OR were adjusted for age and body mass index as potential confounders for OA.
Radiological evidence of knee OA was found in 118 women (12%). For knee OA in either knee the variables significantly associated were raised blood glucose OR = 1.95 (1.08-3.59), and moderately raised serum cholesterol OR = 2.06 (1.06-3.98). For symptomatic women (n = 58) raised blood glucose OR = 2.77 (1.13-6.76), and use of diuretics OR = 2.27 (1.11-4.65) were significantly associated. For bilateral knee disease (n = 55) significant associations were found for ever hypertension OR = 3.02 (1.51-6.06), subjects taking diuretics OR = 2.84 (1.37-5.89), and both high and moderately raised serum cholesterol OR = 3.91 (1.07-14.25), and OR = 3.63 (1.00-13.88), respectively. In all categories of knee OA serum uric acid was nonsignificantly increased. No association was found with raised triglyceride or HDL levels or with current systolic blood pressure. Further adjustment for physical activity and social class did not affect the results.
These data suggest that hypertension, hypercholesterolemia, and blood glucose are associated with both unilateral and bilateral knee OA independent of obesity, and support the concept that OA has an important systemic and metabolic component in its etiology.
One thousand and three women aged 45-64 from the Chingford general population survey were studied cross sectionally to find the effect of quantity and distribution of body fat on the prevalence of radiologically confirmed osteoarthritis (OA) in the knee, carpometacarpal (CMC), distal interphalangeal (DIP), and proximal interphalangeal (PIP) joints. Obesity was classified as the upper tertile of body mass index (BMI kg/m2); the boundaries of the middle tertile were 23.4 and 26.4 kg/m2. The age adjusted odds ratio (OR) [and 95% confidence interval (CI)] of radiographic OA at the knee comparing the high and low tertile of BMI was 6.17 (3.26-11.71) and for bilateral knee radiographic OA was 17.99 (6.25-51.73). Comparing the middle and low tertile of BMI, the odds ratio for radiographic OA knee was 2.86 (1.44-5.68). For other joints the association between BMI and radiographic OA was less strong; the OR at CMC was 1.71 (1.05-2.78), at DIP was 1.52 (0.90-2.57), and at PIP was 1.23 (0.52-2.91). For all joints except PIP these OR increased if the diagnostic criteria included knee pain for at least a month, clinically evident swelling at the DIP or PIP, and pain or tenderness at the CMC. Recalled weight at age 20 years, or recalled maximum weight improved prediction of radiographic OA from current BMI, but measurement of fat distribution from circumference of waist, hip and thigh did not. Our results confirm that excess body weight is a powerful predictor of OA of the knee in middle aged women, and a modest predictor of DIP and CMC OA.(ABSTRACT TRUNCATED AT 250 WORDS)
To explore the relation between noninsulin dependent diabetes mellitus (NIDDM) and osteoarthritis (OA) in a population.
The study population included 632 men and 882 women aged 52-95 years from the Rancho Bernardo community. In 1984-87, participants answered questions about history of diabetes and had a standard oral glucose tolerance (OGTT). In 1988-92, subjects completed a questionnaire about history of arthritis, type of arthritis diagnosed, and presence of joint pain. Nurses examined subjects for presence of Heberden's nodes. Subjects with no history of arthritis were compared to those with a history of OA and other types of arthritis with regard to age, body size, and plasma glucose levels. In addition, subjects were classified by diabetes status to determine differences in the prevalence of arthritis and related characteristics.
Neither impaired glucose tolerance nor NIDDM was associated with history of OA, regardless of how inclusive the definition of OA, before or after adjustment for age and maximum lifetime obesity. In age and obesity adjusted analyses, men with a history of OA had lower fasting plasma glucose levels than men with no arthritis (100.2 vs. 103.6 mg/dl, p < 0.05), and men with NIDDM had less hand and hip pain than normoglycemic men (p < 0.05). Heberden's nodes were unrelated to glucose tolerance status.
This population based study found no positive association between clinical OA and NIDDM defined by OGTT. These results are compatible with community based data examining radiographic OA and history of diabetes.
To assess the association between serum cholesterol and osteoarthritis (OA).
OA patterns were studied in 809 patients with knee or hip joint replacement due to OA in 4 hospitals in southwest Germany. Participants had a standardized interview and examination. Radiographs of the contralateral joint as well as both hands and a blood sample were obtained. Serum cholesterol levels were divided into tertiles and hypercholesterolemia was defined as > or = 6.2 mmol/l or use of antihyperlipidemic drugs. According to the presence or absence of radiographic OA in the contralateral joint, participants were categorized as having bilateral or unilateral OA. If radiographic OA of different finger joints was present, participants were categorized as having generalized OA. Odds ratios and 95% confidence intervals for the association of serum cholesterol with OA patterns were calculated with logistic regression, adjusting for potential confounders.
Eighty-five percent of participants with radiographs had bilateral OA and 26% generalized OA. No association was observed between hypercholesterolemia and bilateral OA. Hypercholesterolemia (OR 1.61; 95% CI 1.06-2.47) and high serum cholesterol levels (3rd versus 1st tertile: OR 1.73; 95% CI 1.02-2.92) were independently associated with generalized OA. This association was almost exclusively due to participants with knee OA.
These data add to the evidence regarding the independent role of serum cholesterol as a systemic risk factor for OA. The discrepant associations observed for different OA patterns are likely due to the relative weight of other risk factors.
Despite recent advances regarding the role of diabetes with respect to cartilage metabolism, epidemiologic data to quantify the role of diabetes in the development of osteoarthritis (OA) are sparse.
OA patterns were studied in 809 patients with knee or hip joint replacement due to OA. NIDDM was defined by a history of physician diagnosed diabetes or use of antihyperglycemics.
Patients with NIDDM had more often bilateral OA (adjusted odds ratio (OR)=2.2; 95% confidence interval (CI): 0.8-6.4). No association between NIDDM and generalized OA (adjusted OR= 1.0; 95%CI: 0.5-1.9) was observed.
Our results are consistent with the hypothesis that NIDDM might be a potentially important systemic risk factor for knee and hip OA, but chance cannot be ruled out as an alternative explanation.
To determine the population-based prevalence of diabetes and other categories of glucose intolerance (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) in Australia and to compare the prevalence with previous Australian data.
A national sample involving 11,247 participants aged > or =25 years living in 42 randomly selected areas from the six states and the Northern Territory were examined in a cross-sectional survey using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma glucose concentrations. The World Health Organization diagnostic criteria were used to determine the prevalence of abnormal glucose tolerance.
The prevalence of diabetes in Australia was 8.0% in men and 6.8% in women, and an additional 17.4% of men and 15.4% of women had IGT or IFG. Even in the youngest age group (25-34 years), 5.7% of subjects had abnormal glucose tolerance. The overall diabetes prevalence in Australia was 7.4%, and an additional 16.4% had IGT or IFG. Diabetes prevalence has more than doubled since 1981, and this is only partially explained by changes in age profile and obesity.
Australia has a rapidly rising prevalence of diabetes and other categories of abnormal glucose tolerance. The prevalence of abnormal glucose tolerance in Australia is one of the highest yet reported from a developed nation with a predominantly Europid background.
To find out the relationship between radiographic osteoarthritis (OA) of the knee, generalized OA and serum cholesterol.
Over a period of 7 months from September 1998 through to March 1999, 246 patients attending 14 primary care clinics in Northern Riyadh, Kingdom of Saudi Arabia, for different non-musculoskeletal complaints were recruited in the study. Their knees, hands and wrists were radiographed. Their ages, sex, weight, height, body mass index (BMI), fasting serum cholesterol, triglycerides and uric acid were recorded.
There were 113 females and 133 males with average ages 46 14.2 and 51.54 16.0 years. One hundred and twenty-two (49.6%) cases of knee OA and 58 (23.6%) cases of generalized OA were found and analyzed for the association with serum cholesterol levels. Crude odds ratio (OR) for the relationship between knee OA and the third tertile of serum cholesterol was 2.33 (95% CI, 1.19-4.58) which on adjusting for age, sex, BMI, serum uric acid and triglycerides were 2.68 (95% CI, 2.00-3.64). For generalized OA, the crude odds ratio (OR) in relation to the third tertile of serum cholesterol was 1.65 (95% CI, 0.78-3.53), adjusted OR was 2.18 (95% CI, 1.55-3.15).
The results showed an association between high serum cholesterol level and both knee and generalized OA.
The aim of this study was to evaluate bone metabolism in patients with bone marrow edema syndrome of the hip. In 37 consecutive patients undergoing core decompression of the femoral head, biochemical markers of bone metabolism were measured in aspirates from cancellous bone and in samples obtained simultaneously from peripheral blood. The diagnosis was made by means of radiographs, magnetic resonance imaging (MRI), and core biopsy specimens. Undecalcified microtome section were available for histopathological evaluation. Bone specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen Type I N-terminal propeptide (PINP), and C-terminal cross-linking telopeptide (ICTP) were studied. Mean serum levels of analytes were 13.1 ng/mL (OC), 11.2 ng/mL (bone ALP), 4.7 ng/mL (ICTP), and 38.8 ng/mL (PINP). In samples obtained from cancellous bone, mean concentrations of all markers were elevated significantly. The mean bone to serum ratios for bone ALP and OC were 14.1 (P=0.005) and 4.1 (P=0.002), respectively. For collagen Type I metabolites, bone to serum ratios averaged 16.3 (P=0.001) for ICTP and 9.6 (P=0.001) for PINP. Markers of bone formation correlated with each other in serum as well as in aspirates from cancellous bone. Elevation of all markers in aspirates from cancellous bone pointed at increased bone turnover, which correlated with histopathological findings of irregularly woven bone, osteoid seams, and lining cells. Mean serum concentrations of all markers, however, were not different from healthy individuals and thus did not provide any useful clue in the diagnosis of this disease. The lack of osteonecrotic regions in our specimens, the marked increase of bone turnover in samples obtained from edematous lesions, and the fact that none of the patients developed osteonecrosis of the femoral head so far seem to further support the contention that transient bone marrow edema syndrome of the hip is a distinct clinical entity.
Several studies of male colon cancer have found positive associations with body size and composition. It is uncertain whether this relationship is due to non-adipose mass, adipose mass, distribution of adipose mass such as central adiposity, or all three.
In a prospective cohort study of men aged 27-75 at recruitment in 1990-1994, body measurements were taken by interviewers. Fat mass and fat-free mass (FFM) were estimated from bioelectrical impedance analysis. Waist circumference and waist-to-hips ratio (WHR) estimated central adiposity. Incident colon cancers were ascertained via the population cancer registry. Altogether, 16,556 men contributed 145,433 person-years and 153 colon cancers.
Rate ratios (RRs) comparing men in the fourth quartile with those in the first quartile were as follows: FFM 2.3 [95% confidence interval (CI) 1.4-3.7]; height 1.9 (95% CI 1.1-3.1); waist circumference 2.1 (95% CI 1.3-3.5); WHR 2.1 (95% CI 1.3-3.4); fat mass 1.8 (95% CI 1.1-3.0); and body mass index 1.7 (95% CI 1.1-2.8). When continuous measures of FFM and WHR were modeled together, the RR for FFM per 10 kg was 1.37 (95% CI 1.04-1.80) and the RR for WHR per 0.1 unit was 1.65 (95% CI 1.28-2.13). After adjustment for FFM and WHR, the RRs for fat mass and body mass index were no longer statistically significant.
Male colon cancer appears to be related to body size and composition by two different pathways, via central adiposity and via non-adipose mass.
Pain is the most common complaint of individuals with osteoarthritis but the cause of symptoms in this disorder remains unclear. Quantitative sensory testing reveals that in patients with chronic joint disease there is diffuse and persistent alteration of nociceptive (pain) pathways, irrespective of the level of activity of the underlying disease. Inflammatory mediators contribute to this plasticity either by directly activating high threshold receptors or more commonly by sensitizing nociceptive neurons to subsequent everyday stimuli. This involves early post-translational modification of receptors/ion channels and later, longer-lasting transcription-dependent mechanisms involving changes to the chemical phenotype of the neuron. Included amongst these changes are the increased production and release of various pro- and anti-inflammatory neuropeptides which have diverse actions on both circulating and resident cell populations. These neurally derived mediators act synergistically with cytokines and growth factors to contribute to ongoing tissue injury. It is becoming apparent that the interaction between a damaged joint and the sensory nervous system is far from straightforward and that activity arising from such interactions may produce not only pain but may also influence the subsequent course of the underlying disease.
This new definition should assist both researchers and clinicians.