Adolfo Díez-Pérez

Instituto de Salud Carlos III, Madrid, Madrid, Spain

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Publications (149)589.35 Total impact

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    ABSTRACT: This consensus article reviews the diagnosis and treatment of osteoporosis in geriatric populations. Specifically, it reviews the risk assessment and intervention thresholds, the impact of nutritional deficiencies, fall prevention strategies, pharmacological treatments and their safety considerations, the risks of sub-optimal treatment adherence and strategies for its improvement.
    07/2014;
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    ABSTRACT: We used a large population-based health care database to determine the impact of common co-morbidities on hip fracture risk amongst elderly men. We demonstrated that diabetes, chronic obstructive pulmonary disease, renal failure, HIV infection, dementia, and cerebrovascular disease are independent predictors of hip fracture, as is a Charlson score of ≥3. Risk factors for hip fractures in men are still unclear. We aimed to identify common co-morbidities (amongst those in the Charlson index) that confer an increased risk of hip fracture amongst elderly men. We conducted a population-based cohort study using data from the SIDIAP (Q) database. SIDIAP(Q) contains primary care and hospital inpatient records of a representative 30 % of the population of Catalonia, Spain (>2 million people). All men aged ≥65 years registered on 1 January 2007 were followed up until 31 December 2009. Both exposure (co-morbidities in the Charlson index) and outcome (incident hip fractures) were ascertained using ICD codes. Poisson regression models were fitted to estimate the effect of (1) each individual co-morbidity and (2) the composite Charlson index score, on hip fracture risk, after adjustment for age, body mass index, smoking, alcohol drinking, and use of oral glucocorticoids. We observed 186,171 men for a median (inter-quartile range) of 2.99 (2.37-2.99) years. In this time, 1,718 (0.92 %) participants had a hip fracture. The following co-morbidities were independently associated with hip fractures: diabetes mellitus, chronic obstructive pulmonary disease (COPD), renal failure, HIV infection, dementia, and cerebrovascular disease. A Charlson score of ≥3 conferred an increased hip fracture risk. Common co-morbidities including diabetes, COPD, cerebrovascular disease, renal failure, and HIV infection are independently associated with an increased risk of hip fracture in elderly men. A Charlson score of 3 or more is associated with a 50 % higher risk of hip fracture in this population.
    Osteoporosis International 03/2014; · 4.04 Impact Factor
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    ABSTRACT: Fractures in obese older individuals contribute significantly to the overall burden, but data on their impact on mortality are lacking. We studied the association between obesity and mortality following hip and non-hip clinical fractures in a retrospective, population-based cohort study. The SIDIAP(Q) database contains primary care computerized medical records of a representative sample of >2.1 million people (35% of the population) in Catalonia (Spain), linked to hospital admissions data. We included in this analysis anyone aged 40 years and older suffering a hip or non-hip clinical fracture in 2007-2009 in the SIDIAP(Q) database. The main exposure was the most recent body mass index (BMI) measured before fracture, categorized as underweight (<18.5 kg/m(2) ), normal (18.5 to <25 kg/m(2) ), overweight (25 to <30 kg/m(2) ) and obese (≥30 kg/m(2) ). Furthermore, the study outcome was all-cause mortality in 2007-2009 as provided to SIDIAP(Q) by the National Office of Statistics. Time to death after fracture was modelled using Cox regression. Multivariate models were adjusted for age, gender, smoking, alcohol intake, oral glucocorticoid use, and Charlson co-morbidity Index. Within the study period, 6,988 and 29,372 subjects with a hip or non-hip clinical fracture were identified and followed for a median (inter-quartile range) of 1.17(0.53-2.02) and 1.36(0.65-2.15) years, respectively. Compared to subjects of normal weight, adjusted hazard ratios (HR) for mortality in overweight and obese subjects were 0.74 (95%CI 0.62-0.88; p = 0.001) and 0.74 (0.60-0.91; p = 0.004) after hip and 0.50 (0.32-0.77; p = 0.002), 0.56 (0.36-0.87; p = 0.010) after non-hip fracture. In conclusion, the highest mortality was observed in individuals with low BMI, but compared to subjects of normal weight, obese and overweight individuals survived longer following fracture. The latter observation is consistent with data reported in other chronic conditions, but the reasons for reduced mortality in obese and overweight subjects when compared to those of normal weight require further research. © 2014 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2014; · 6.04 Impact Factor
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    ABSTRACT: Different studies have reported an association between HIV infection, antiretroviral therapies and impaired bone metabolism, but data on their impact on fracture risk are scarce. We studied the association between a clinical diagnosis of HIV infection and fracture risk. We conducted a case-control study using data from the Danish National Health Service registries, including 124,655 fracture cases and 373,962 age-gender-matched controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. A total of 50 (0.40/1,000) patients in the fracture group and 52 (0.14/1,000) controls had a HIV diagnosis. The risk of any fracture was thus significantly increased among HIV-infected patients (age and gender-matched OR = 2.89, 95% CI 1.99-4.18). Similarly, significant increases in the risk of hip (OR=8.99, 95% CI 1.39-58.0), forearm (OR=3.50, 95 CI 1.26-9.72), and spine fractures (OR=9.00, 95% CI 1.39-58.1) were observed. HIV infection is associated with an almost 3-fold increase in fracture risk compared to that of uninfected age and gender-matched uninfected patients. HIV patients are also at an almost 9-fold higher risk of hip fracture.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2014; · 4.65 Impact Factor
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    ABSTRACT: Osteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequence is bone fractures, which often lead to patient disability or even death. Currently, there are a number of commercial biomaterials used to treat osteoporotic bone fractures, but most of them have not been specifically designed for that purpose. Simultaneously, many drug- or cell-loaded biomaterials have been proposed in research laboratories, but hardly any has received approval for commercial use. In order to analyze this scenario and propose alternatives to overcome this scenario, the Spanish and European Network of Excellence for the Prevention and Treatment of Osteoporotic Fractures "Ageing" was created. This network integrates three communities, e. g. clinicians, materials scientists and industrial advisors, tackling the same problem from three different points of view. Keeping in mind the premise "living longer, living better", this commentary is the result of the thoughts, proposals and conclusions obtained after one year working in the framework of this network.
    Acta biomaterialia 01/2014; · 5.09 Impact Factor
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    ABSTRACT: Background Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. Methods In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator - oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. Results All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. Conclusions In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532 .).
    New England Journal of Medicine 01/2014; · 51.66 Impact Factor
  • Applied Surface Science 01/2014; 307:246–254. · 2.54 Impact Factor
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    ABSTRACT: From 50 years of age, postmenopausal women are at an increased risk of developing sarcopenia and osteoporosis as a result of deterioration of musculoskeletal health. Both disorders increase the risk of falls and fractures. The risk of developing sarcopenia and osteoporosis may be attenuated through healthy lifestyle changes, which include adequate dietary protein, calcium and vitamin D intakes, and regular physical activity/exercise, besides hormone replacement therapy when appropriate. Protein intake and physical activity are the main anabolic stimuli for muscle protein synthesis. Exercise training leads to increased muscle mass and strength, and the combination of optimal protein intake and exercise produces a greater degree of muscle protein accretion than either intervention alone. Similarly, adequate dietary protein intake and resistance exercise are important contributors to the maintenance of bone strength. Vitamin D helps to maintain muscle mass and strength as well as bone health. These findings suggest that healthy lifestyle measures in women aged >50 years are essential to allow healthy aging. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommends optimal dietary protein intake of 1.0–1.2 g/kg body weight/d with at least 20–25 g of high-quality protein at each main meal, with adequate vitamin D intake at 800 IU/d to maintain serum 25-hydroxyvitamin D levels >50 nmol/L as well as calcium intake of 1000 mg/d, alongside regular physical activity/exercise 3–5 times/week combined with protein intake in close proximity to exercise, in postmenopausal women for prevention of age-related deterioration of musculoskeletal health.
    Maturitas 01/2014; · 2.84 Impact Factor
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    ABSTRACT: Context. Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired. Objective. To improve model discrimination by developing a 5-yr composite fracture prediction model for fracture sites that display similar risk profiles. Design. Prospective, observational cohort study. Setting. Primary care practices in 10 countries. Patients. Women aged ≥55 years. Intervention. Self-administered questionnaires collected data on patient characteristics, fracture risk factors and previous fractures. Main Outcome Measure. Main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age. Results. Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index 0.75, 47,066 women), and lowest for FRAX major fracture and a 10-site model (c indices 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 yr of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 yr of age from a 10% decrease to a 60% increase. Conclusions. After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
    The Journal of clinical endocrinology and metabolism 01/2014; · 6.50 Impact Factor
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    ABSTRACT: The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM.
    PLoS ONE 01/2014; 9(4):e94607. · 3.73 Impact Factor
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    ABSTRACT: Temporal trends in hip fracture incidence have recently been reported in some developed countries. Such data in Spain has previously been incomplete; this study reports the stratified incidence of hip fractures in people over 65 in Spain during the last 14 years. The main objective is to establish whether temporal trends in hip fracture incidence in Spain exist. Ecological study with data from hospital discharges nationwide. The study includes patients aged ≥65 years during a 14-year period (1997-2010). The analysis compares two periods of four years: 1997-2000 (P1) and 2007-2010 (P2). There were 119,857 fractures in men and 415,421 in women. Comparing periods (P1 vs P2) over 10 years, the crude incidence rate/100,000 inhabitant/year increased an average of 2.3 %/year in men and 1.4 % in women. After adjustment, the rate increased an average of 0.4 %/year in men (p < 0.0001), but decreased 0.2 %/year in women (p < 0.0001). In men, younger than 85, the decrease was not significant except in 70-74 years, and from 80 years, the adjusted rate increases significantly (p < 0.0001). In women under 80 years of age, the decrease in adjusted rate was significant; there was no change in 80-84 years, and the adjusted rate increased significantly in individuals 85 years and older (p < 0.0001). Mortality rates declined by 22 % in both sexes, and the index of overaging population rises 30.1 % in men and 25.2 % in women. This study supports other international studies by showing changes in the incidence of hip fractures after age-population adjustment, which denotes a decrease in the younger age groups and among women and shows an increase in both groups over 85 years. The increase in the crude incidence rate of hip fracture in Spain reflects changes in population structure.
    Osteoporosis International 12/2013; · 4.04 Impact Factor
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    ABSTRACT: A novel, hand-held Reference Point Indentation (RPI) instrument, measures how well the bone of living patients and large animals resists indentation. The results presented here are reported in terms of Bone Material Strength, which is a normalized measure of how well the bone resists indentation, and is inversely related to the indentation distance into the bone. We present examples of the instrument's use in: (1) laboratory experiments on bone, including experiments through a layer of soft tissue, (2) three human clinical trials, two ongoing in Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two ongoing horse clinical trials, one at Purdue University and another at Alamo Pintado Stables in California. The instrument is capable of measuring consistent values when testing through soft tissue such as skin and periosteum, and does so handheld, an improvement over previous Reference Point Indentation instruments. Measurements conducted on horses showed reproducible results when testing the horse through tissue or on bare bone. In the human clinical trials, reasonable and consistent values were obtained, suggesting the Osteoprobe(®) is capable of measuring Bone Material Strength in vivo, but larger studies are needed to determine the efficacy of the instrument's use in medical diagnosis.
    Journal of Medical Devices 12/2013; 7(4):410051-410056. · 0.71 Impact Factor
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    ABSTRACT: Osteoporosis is defined as a reduction in bone mass and impairment of bone quality that lead to bone fragility and fracture risk. Bone quality includes a hierarchy of properties from macroscopic to nanoscale level. Several techniques have been developed in an attempt to measure these non-density properties. Densitometry, high-resolution images (radiography, CT scan), and MRI can measure the geometry and microarchitecture of bone. Tissue mineralization and composition can be assessed by use of microradiography, Fourier-transform infrared spectroscopy, or Raman microspectroscopy. Finite-element analysis is an image-based method that enables calculation of bone strength. More recently, microindentation has enabled direct estimation of bone material strength, measured in the cortical bone of the tibia. Most of these techniques are of limited use to clinics, although finite-element analysis and microindentation have high potential for clinical use and can enable more comprehensive and accurate evaluation of bone fragility and fracture susceptibility.
    Current Rheumatology Reports 11/2013; 15(11):373.
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    Erik F Eriksen, Adolfo Díez-Pérez, Steven Boonen
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    ABSTRACT: Osteoporosis is a progressive skeletal disorder that requires long-term treatment. However, there is little guidance regarding optimal treatment duration and what the treatment discontinuation and retreatment criteria should be. Given that bisphosphonates are the most commonly prescribed class of agent for the treatment of osteoporosis, we reviewed the long-term data relating to these therapies and discussed the considerations for using bisphosphonates in postmenopausal women with osteoporosis. A PubMed search, using the search terms 'bisphosphonate', 'postmenopausal osteoporosis' and 'long term' and/or 'extension' was conducted in January 2013. Results from 9 controlled studies that prospectively assessed alendronate, risedronate, ibandronate or zoledronic acid in women with postmenopausal osteoporosis were reviewed. Clinical studies in postmenopausal women with osteoporosis showed that long-term use of bisphosphonates resulted in persistent antifracture and bone mineral density (BMD) increasing effects beyond 3years of treatment. No unexpected adverse events were identified in these studies and the long-term tolerability profiles of bisphosphonates remain favorable. Data from the withdrawal extension studies of alendronate and zoledronic acid also showed that residual fracture benefits were seen in patients who discontinued treatment for 3 to 5years after an initial 3- to 5-year treatment period. BMD monitoring and fracture risk assessments should be conducted regularly to determine whether treatment could be stopped or should be reinitiated. Patients exhibiting T-scores<-2.5 or who have suffered a new fracture while on treatment should continue treatment, while patients with T-scores>-2.5 could be considered for discontinuation of active treatment while undergoing continued monitoring of their bone health. The duration and potential discontinuation of treatment should be personalized for individual patients based on their response to treatment, fracture risk and comorbidities.
    Bone 10/2013; · 3.82 Impact Factor
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    ABSTRACT: Fractures may be associated with higher morbidity in obese postmenopausal women than in nonobese women. We compared health-care utilization, functional status, and health-related quality of life (HRQL) in obese, nonobese, and underweight women with fractures. Information from the GLOW study, started in 2006, was collected at baseline and at 1, 2, and 3 years. In this subanalysis, self-reported incident clinical fractures, health-care utilization, HRQL, and functional status were recorded and examined. Women in GLOW (n = 60,393) were aged ≥55 years, from 723 physician practices at 17 sites in 10 countries. Complete data for fracture and body mass index were available for 90 underweight, 3,270 nonobese, and 941 obese women with one or more incident clinical fractures during the 3-year follow-up. The median hospital length of stay, adjusted for age, comorbidities, and fracture type, was significantly greater in obese than nonobese women (6 vs. 5 days, p = 0.017). Physical function and vitality score were significantly worse in obese than in nonobese women, both before and after fracture; but changes after fracture were similar across groups. Use of antiosteoporosis medication was significantly lower in obese than in nonobese or underweight women. In conclusion, obese women with fracture undergo a longer period of hospitalization for treatment and have poorer functional status and HRQL than nonobese women. Whether these differences translate into higher economic costs and adverse effects on longer-term outcomes remains to be established.
    Calcified Tissue International 09/2013; · 2.50 Impact Factor
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    ABSTRACT: Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles. Introduction We compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW). Methods GLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged ≥55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures. Results In total 2,945/43,832 (6.8 %) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95 % confidence interval [CI], 3.89; 2.78–5.44), multiple sclerosis (2.70; 1.90–3.83), cerebrovascular events (2.02; 1.67–2.46), and rheumatoid arthritis (2.15; 1.53–3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46 %) or lower than (36 %) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29 % experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74–3.29) compared with women without morbidities. Conclusions Postmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease.
    Osteoporosis International 07/2013; · 4.04 Impact Factor
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    ABSTRACT: A major side effect of aromatase inhibitor (AI) therapy is AI-related arthralgia (AIA), which often leads to therapy discontinuation. We aimed to identify genetic variants associated with AIA and therapy discontinuation in the first year of AI treatment. Our prospective cohort study included 343 postmenopausal women with early breast cancer starting AI therapy. Single nucleotide polymorphisms (SNPs) in candidate genes involved in estrogen and vitamin D signaling were selected. Univariate and multivariate linear/logistic regressions were fitted in order to asses the association between studied SNPs and AIA intensity (visual analogic scale score) at 3 and 12 months of follow-up, worsening pain, and therapy discontinuation. We also tested for a priori-defined interactions by introducing multiplicative terms in the regression equations. SNPs in CYP17A1 and VDR genes appeared significantly associated with AIA (P = 0.003, P = 0.012, respectively). One SNP in CYP27B1 gene was related to therapy discontinuation [P = 0.02; OR 0.29 (0.09-0.99)]. We revealed interactions between CYP27B1 and both CYP17A1 (P = 0.01) and VDR SNPs (P = 0.06). Furthermore, an additive effect on pain intensity was shown for unfavorable alleles, with two points higher mean absolute pain increase and up to 5.3-fold higher risk of worsening pain compared to favorable genotypes. SNPs in CYP17A1, VDR, and CYP27B1 genes predict the risk of AIA. Their determination would be useful to trigger the monitoring strategies in women at risk of therapy discontinuation.
    Breast Cancer Research and Treatment 07/2013; · 4.47 Impact Factor
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    ABSTRACT: Anti-osteoporosis medication (AOM) does not abolish fracture risk, and some individuals experience multiple fractures while on treatment. Therefore, criteria for treatment failure have recently been defined. Using data from the Global Longitudinal study of Osteoporosis in Women (GLOW), we analyzed risk factors for treatment failure, defined as sustaining ≥2 fractures while on AOM. GLOW is a prospective, observational cohort study of women aged ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires collected data on patient characteristics, fracture risk factors, previous fractures, AOM use, and health status. Data were analyzed from women who used the same class of AOM continuously over 3 survey-years and had data available on fracture occurrence. Multivariable logistic regression was used to identify independent predictors of treatment failure. Data from 26,918 women were available, of whom 5550 were on AOM. During follow-up, 73/5550 women in the AOM group (1.3%) and 123/21,368 in the non-AOM group (0.6%) reported occurrence of ≥2 fractures. The following variables were associated with treatment failure: lower SF-36 score (physical function and vitality) at baseline, higher FRAX score, falls in the past 12 months, selected comorbid conditions, prior fracture, current use of glucocorticoids, need of arms to assist to standing, and unexplained weight loss ≥10 lb (≥4.5 kg). Three variables remained predictive of treatment failure after multivariable analysis: worse SF-36 vitality score (odds ratio [OR] per 10-point increase 0.85; 95% confidence interval [CI] 0.76-0.95; p = 0.004), ≥2 falls in the past year (OR 2.40; 95% CI 1.34-4.29; p = 0.011), and prior fracture (OR 2.93; 95% CI 1.81-4.75; p < 0.0001). The C statistic for the model was 0.712. Specific strategies for fracture prevention should therefore be developed for this subgroup of patients.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2013; · 6.04 Impact Factor
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    ABSTRACT: Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 years (range 20-105 years) and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6,457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI≥30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR, 95% CI) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (0.85-0.90). When adjusted for BMD, however, the same comparison showed that the hazard ratio for osteoporotic fracture was increased (HR= 1.16; 95% CI = 1.09 - 1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2013; · 6.04 Impact Factor
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    ABSTRACT: Although oral bisphosphonates (BP) are highly effective in preventing fractures, some patients will fracture while on treatment. We identified predictors of such fractures in a population-based cohort of incident users of oral BP. We screened the SIDIAP database to identify new users of oral BP in 2006-2007. SIDIAP includes pharmacy invoice data and primary care electronic medical records for a representative 5 million people in Catalonia (Spain). Exclusion criteria were: Paget disease, <40 years of age, and any anti-osteoporosis treatment in the previous year. A priori defined risk factors included age, gender, body mass index, vitamin D deficiency, smoking, alcohol drinking, pre-existing comorbidities, and medications. Fractures were considered if they appeared after at least 6 months after treatment initiation. Fractures while on treatment were defined as those occurring among participants persisting for at least 6 months and with an overall high compliance (medication possession ratio ≥ 80%). Fine and Gray survival models accounting for competing risk with therapy discontinuation were fitted to identify key predictors. RESULTS: Only 7,449/21,385 (34.8%) participants completed >6 months of therapy. Incidence of "fracture while on treatment" was 3.4/100 person-years [95%CI 3.1-3.7]. Predictors of these among patients persisting and adhering to treatment included: older age (sub-hazard ratio (SHR) for 60 to <80 years 2.18 [1.70-2.80]; for ≥80years 2.5 [1.82-3.43]), previous fracture (SHR 1.75 [1.39-2.20] and 2.49 [1.98-3.13] in the last 6 months and longer respectively), underweight (SHR 2.11 [1.14-3.92]), inflammatory arthritis (SHR 1.46 [1.02-2.10]), use of proton pump inhibitors (PPI) (SHR 1.22 [1.02-1.46]) and vitamin D deficiency (SHR 2.69 [1.27-5.72]. CONCLUSION(S): Even among high compliers, 3.4% of oral BP users will fracture every year. Older age, underweight, vitamin D deficiency, PPI use, previous fracture and inflammatory arthritides increase risk. Monitoring strategies and/or alternative therapies should be considered for these patients.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2013; · 6.04 Impact Factor

Publication Stats

2k Citations
589.35 Total Impact Points

Institutions

  • 2010–2014
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
  • 2009–2014
    • IMIM Hospital del Mar Medical Research Institute
      Barcino, Catalonia, Spain
  • 2013
    • Cambridge University Hospitals NHS Foundation Trust
      Cambridge, England, United Kingdom
  • 2003–2013
    • Parc de Salut Mar
      Barcino, Catalonia, Spain
  • 2002–2013
    • Autonomous University of Barcelona
      • Departamento de Medicina
      Cerdanyola del Vallès, Catalonia, Spain
  • 2011
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
    • Centro de Investigación Biomédica en Red de Enfermedades Raras
      Valenza, Valencia, Spain
    • Alfried Krupp Krankenhaus
      Essen, Lower Saxony, Germany
  • 2008–2011
    • Universidad de Cantabria
      Santander, Cantabria, Spain
  • 2000–2011
    • University of Barcelona
      • • Departament de Medicina
      • • Departament de Genètica
      Barcelona, Catalonia, Spain
  • 2007–2008
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2006
    • The University of Edinburgh
      • Rheumatic Diseases Unit
      Edinburgh, SCT, United Kingdom
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
    • Eli Lilly
      Indianapolis, Indiana, United States
  • 2004
    • University of California, San Francisco
      San Francisco, California, United States
  • 2001
    • Consorci MAR Parc de Salut de Barcelona
      Barcino, Catalonia, Spain