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Mickael Hiligsmann,
John A Kanis,
Juliet Compston,
Cyrus Cooper,
Bruno Flamion,
Pierre Bergmann,
Jean-Jacques Body,
Steven Boonen,
Olivier Bruyere,
Jean-Pierre Devogelaer,
Stefan Goemaere, Jean-Marc Kaufman,
Serge Rozenberg,
Jean-Yves Reginster
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ABSTRACT: We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of health-care resources by decision makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society, with lifetime risks of any fracture of the hip, spine, and forearm of around 40 % for women and 13 % for men. The economic impact is also large; for example, Europe's six largest countries spent 31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture-risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision makers in health care on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce health-care resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision makers efficiently allocate health-care resources.
Calcified Tissue International 03/2013; · 2.38 Impact Factor
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ABSTRACT: The study aim was to investigate the health effects of a pedometer-based behavioural modification program in type 2 diabetes patients and to examine the relationship between changes in steps/day (baseline-post and baseline-follow up) and health outcomes. Ninety-two type 2 diabetes patients (69% male, mean age: 62 ± 9 years and mean BMI: 30.0 ± 2.5 kg/m(2)) were recruited and randomly assigned to an intervention or control group. The intervention consisted of one face-to-face session, pedometer use and seven telephone calls. Selection criteria included 35-75 years, 25-35 kg/m(2) and ≤12% HbA1c (108 mmol/mol). Outcome measures were assessed at baseline, post and follow up, and included systolic blood pressure, waist circumference, body mass index, glucose control (HbA1c and fasting glucose), triglycerides, total, HDL and LDL cholesterol and steps/day. The results showed no significant short- or intermediate-term differences in health outcomes between the control and intervention group. However, a threshold was identified, as HbA1c improved significantly in those who increased ≥4000 steps/day between baseline- and post-measurements (n = 18). This threshold was not applicable to any other health outcome. Hence, although the intervention successfully increased steps/day, no direct effect on health outcomes was identified. However, an increase of ≥4000 steps/day seemed a threshold to have a positive impact on HbA1c.
Health Education Research 03/2013; · 1.66 Impact Factor
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ABSTRACT: OBJECTIVE: Sclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in the less efficient bone acquisition in men with idiopathic low bone mass, this might be reflected in higher serum sclerostin levels. METHODS: In 116 men with idiopathic osteoporosis (<65 yrs), 40 of their sons and healthy controls, areal bone parameters were measured using dual energy X-ray absorptiometry, volumetric and geometric bone parameters using peripheral quantitative computed tomography. Serum analytes were measured using immunoassays, estradiol levels using liquid chromatography-tandem mass spectrometry. RESULTS: Men with idiopathic low bone mass had lower levels of sclerostin than controls (0.54±0.17 vs. 0.66±0.23 ng/mL; p<0.001). In both groups, sclerostin levels were strongly associated with age; when adjusting for age, no associations with anthropometrics were observed (p>0.14). In multivariate analyses, sclerostin levels displayed a positive association with whole body BMC and aBMD, as well as with trabecular and cortical vBMD at the tibia in the probands. No clear associations were observed in the control group, neither were sclerostin levels associated with BMC at the radius or lumbar spine (all p>0.11). Testosterone, but not estradiol, was inversely related to sclerostin levels in the probands. No difference in sclerostin levels was found in their sons as compared to their controls. CONCLUSION: Lower rather than higher serum sclerostin levels in probands with idiopathic low bone mass suggest that aberrant sclerostin secretion is not involved in the pathogenesis of low bone mass in these subjects.
European Journal of Endocrinology 02/2013; · 3.42 Impact Factor
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ABSTRACT: Background Triiodothyronine (T3) has many effects on the heart and marked changes in cardiac function and structure occur in patients with (subclinical) thyroid disease. We investigated whether between-subject variation in thyroid hormone levels within the euthyroid range is also associated with heart rate and echocardiographic heart function and structure. Methods Subjects were selected from the Asklepios study (n=2524), a population-representative random sample between 35 and 55 yrs, free from overt cardiovascular disease at baseline. Analyses were restricted to 2078 subjects (1013 women and 1065 men), not using antihypertensive or thyroid medication nor having anti-TPO levels above clinical cut-off or TSH levels outside the reference range. All subjects were phenotyped in-depth and underwent comprehensive echocardiography, including diastolic evaluation. Thyroid function parameters were determined by automated electrochemiluminescence. Results Heart rate was robustly positively associated with (quartiles of) (F)T3, both in subjects with TSH levels within reference (0.27-4.2 µU/l) as in narrow TSH-range (0.5-2.5 µU/l) (p≤0.0001). (F)T3 was negatively associated with LV (left ventricular) end-diastolic volume but positively with relative wall thickness. TT3 was associated with enhanced ventricular contraction (as assessed by tissue Doppler imaging). FT4, FT3 and TT3 were positively associated with late ventricular filling, and TT3 was associated with early ventricular filling. Conclusion We have demonstrated a strong positive association between thyroid hormone levels within the euthyroid range and heart rate, and more subtle effects on cardiac function and structure. More specifically, we suggest smaller LV cavity size (with increased relative wall thickness), an enhanced atrial and ventricular contraction and LV relaxation with higher circulating thyroid hormones. These results illustrate that variation of thyroid hormone levels even within the reference range exerts effects on the heart.
Thyroid: official journal of the American Thyroid Association 01/2013; · 2.60 Impact Factor
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ABSTRACT: BACKGROUND: To assess and compare the predictive value of physical function measurements (PFMs) for all-cause mortality in older men and to evaluate the Timed Up and Go test (TUG) as a predictor in subjects with underlying comorbidity. DESIGN: Observational study of a population-based sample of 352 ambulatory older men aged 71-86 at study baseline. The Rapid disability rating scale-2, 36-Item short form health survey, Grip strength, Five times sit-to-stand test, Standing balance, and TUG were determined at baseline. Associations with all-cause mortality were assessed using Cox proportional hazard analyses. Age, Body mass index (BMI), smoking status, education, physical activity and cognitive status were included as confounders. Follow-up exceeded 15 years. Comorbidity status was categorized into cardiovascular disease, chronic obstructive pulmonary disease (COPD) and diabetes mellitus. RESULTS: All examined PFMs were associated with all-cause mortality. TUG was the best predictor (adjusted HR per SD increase = 1·58, 95% CI = 1·40-1·79, P < 0·001) for global mortality and continued to be predictive in subjects with cardiovascular disease (adjusted HR per SD increase = 1·80, 95% CI = 1·40-2·33, P < 0·001). CONCLUSIONS: The assessment of physical functioning is important in the evaluation of older persons. We encourage the use of the TUG as a reliable, quick and feasible screening tool in clinical settings.
European Journal of Clinical Investigation 01/2013; · 3.02 Impact Factor
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Thyroid: official journal of the American Thyroid Association 12/2012; · 2.60 Impact Factor
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ABSTRACT: Studies reporting associations between genetic factors and mood-related traits have often been critized (i) for failing to take into account the role of the social environment in which individuals act and (ii) for not maintaining a 'transparent narrative connection' between genes and outcomes. In a sample of adolescents, we analyzed whether PvuII and XbaI, two polymorphisms on the ESR1 (Estrogen Receptor Gene α) were related to depressive symptoms, and considered whether daily hassles moderated this relationship and whether anger expression style mediated this relationship. Analyses suggested that ESR1 polymorphisms are relevant to the intra-sexual variability in depressive symptoms in boys and that the experience of daily hassles moderated this relationship. No such relationships were found in girls. Additionally, ESR1 polymorphisms are related to anger expression styles in girls. Anger-related variables, however, did not mediate the relationship between ESR1 polymorphisms and depressive symptoms, in boys nor in girls.
Hormones and Behavior 11/2012; · 3.87 Impact Factor
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Steven Boonen,
Jean-Yves Reginster, Jean-Marc Kaufman,
Kurt Lippuner,
Jose Zanchetta,
Bente Langdahl,
Rene Rizzoli,
Stanley Lipschitz,
Hans Peter Dimai,
Richard Witvrouw, [......],
Luis Russo,
Frank Claessens,
Philemon Papanastasiou,
Oscar Antunez,
Guoqin Su,
Christina Bucci-Rechtweg,
Josef Hruska,
Elodie Incera,
Dirk Vanderschueren,
Eric Orwoll
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ABSTRACT: Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.
In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months.
The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P=0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss (P=0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%).
Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.).
New England Journal of Medicine 11/2012; 367(18):1714-23. · 53.30 Impact Factor
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ABSTRACT: Thyroid disorders affect metabolism and body composition. Existing literature has been conflicting on whether this is also the case for thyroid hormone levels within the euthyroid range. Therefore, we have investigated the relationship between thyroid hormone concentrations and body composition together with metabolic parameters in a population of healthy euthyroid men.
Healthy male siblings (n=941, 25-45 years, median BMI 24.6) were recruited in a cross-sectional, population-based study; a history or treatment of thyroid disease and thyroid autoimmunity were exclusion criteria. Body composition and muscle cross-sectional area were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Total (triiodothyronine (T(3); TT(3)) thyroxine and (T(4); TT(4))) and free thyroid hormones (FT(3) and FT(4)), TSH, and reverse T(3) (rT(3)) and thyroid-binding globulin (TBG) were determined using immunoassays.
BMI was positively associated with (F)T(3) (P<0.0001). Whole body fat mass displayed positive associations with TT(3) and with (F)T(4) and TBG (P≤0.0006). Positive associations were further observed between leptin and (F)T(3), TT(4), and TBG (P≤0.0002). Inverse associations between lean mass and muscle cross-sectional area and (F)T(3), (F)T(4), and TBG were observed (P≤0.0003). Higher levels of (F)T(3) and TBG were associated with lower insulin sensitivity, assessed by homeostatic model assessment of insulin resistance (IR; P≤0.0001). No associations between TSH and body composition or metabolic parameters were seen.
We show that a less favorable body composition (with higher fat and lower muscle mass and accompanying higher leptin concentrations) and IR are associated with higher thyroid hormone levels in healthy young men with well characterized euthyroidism.
European Journal of Endocrinology 09/2012; 167(5):719-26. · 3.42 Impact Factor
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ABSTRACT: The literature provides no clear answer as to whether total oestradiol (E2) concentrations increase the risk of incident cardiovascular disease (CVD) in healthy men.
The authors conducted a systematic review and meta-analysis to estimate the predictive value of E2 for CVD, and to identify study features explaining conflicting results.
Articles were identified by a Medline and Embase search and citation tracking.
Eligible articles were prospective population-based cohorts and nested case-control studies on E2 and incident cardiovascular disease (CVD), including myocardial infarction, stroke or death from coronary heart disease. DATA-EXTRACTION: Independent researchers re-expressed associations of E2 and incident CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of E2 for CVD.
14 studies out of 128 electronically identified articles were eligible. Data to be used for meta-analysis could be calculated in seven cases, and in the remaining seven cases, data of three more became available by contacting those authors. Overall, a non-significant association was found with an estimated summary RR of 0.98 for a change of >75th versus <25th percentile in E2 (95% CI 0.74 to 1.31). Mean body mass index (BMI) of the study population (βs -0.8, p<0.004), and quality of E2 assay (βs -0.6, p<0.08) may have modified the relationship between E2 and incident CVD. The present systematic review does not provide evidence for a pronounced harmful or beneficial effect of E2 on risk for incident CVD in healthy men. If present, an effect of E2 on risk for CVD might be modulated by BMI.
Heart (British Cardiac Society) 06/2012; 98(20):1478-82. · 4.22 Impact Factor
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Johannes B Ruige,
Marlies Bekaert,
Bruno Lapauw,
Tom Fiers,
Stefan Lehr,
Sonja Hartwig,
Daniella Herzfeld de Wiza,
Martina Schiller,
Waltraud Passlack,
Yves Van Nieuwenhove,
Piet Pattyn,
Claude Cuvelier,
Youri E Taes,
Henrike Sell,
Juergen Eckel, Jean-Marc Kaufman,
D Margriet Ouwens
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ABSTRACT: Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men.
The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines.
Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches.
Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo.
Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.
The Journal of clinical endocrinology and metabolism 04/2012; 97(7):E1187-91. · 6.50 Impact Factor
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D Margriet Ouwens,
Marlies Bekaert,
Bruno Lapauw,
Yves Van Nieuwenhove,
Stefan Lehr,
Sonja Hartwig,
Patrick Calders, Jean-Marc Kaufman,
Henrike Sell,
Juergen Eckel,
Johannes B Ruige
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ABSTRACT: To allow early detection and prevention of metabolic disorders, circulating levels of adipokines involved in insulin sensitivity were compared with the hyperinsulinemic-euglycemic clamp. Twenty non-obese normo-glycaemic men (age 32.1 ± 6 years) underwent a clamp procedure. Levels of leptin, adiponectin, resistin, visfatin, omentin and chemerin levels were determined in fasting blood samples. Pearson correlation coefficients between the M-value for insulin sensitivity and fasting levels of chemerin (r = -0.63, P = 0.003) and leptin (r = -0.54, P = 0.013) performed better than conventional surrogate measures of insulin sensitivity (HOMA-IR: r = -0.45, P = 0.048; Quicki: r = 0.36, P = 0.12). However, only the relation between M-value(LBM) and chemerin remained significant when adjusting for BMI and fasting insulin levels (r = -0.559, P = 0.016). In conclusion, fasting levels of chemerin might be used as biomarker to identify insulin resistance in healthy men without typical characteristics of metabolic disorders.
Archives of Physiology and Biochemistry 02/2012; 118(3):135-8.
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ABSTRACT: Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2.
913 obese females unknown to have diabetes were recruited (mean age: 41.2±SD 12.3; median BMI: 36.2, IQR 32.9-40.2). Visceral (VAT) and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test.
Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT), and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT). Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared.
Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.
PLoS ONE 01/2012; 7(9):e45145. · 4.09 Impact Factor
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Steven Boonen,
Eric Orwoll,
Jay Magaziner,
Cathleen S Colón-Emeric,
Jonathan D Adachi,
Christina Bucci-Rechtweg,
Patrick Haentjens, Jean-Marc Kaufman,
Rene Rizzoli,
Dirk Vanderschueren,
Frank Claessens,
An Sermon,
Richard Witvrouw,
Koen Milisen,
Guoqin Su,
Kenneth W Lyles
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ABSTRACT: To assess the efficacy of once-yearly zoledronic acid (ZOL) 5 mg in increasing bone mineral density (BMD) in men with a recent hip fracture participating in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once- Yearly Recurrent Fracture Trial and to compare the efficacy with that in women from the same study.
Randomized, placebo-controlled, double-blind trial.
International multicenter.
Five hundred and eight men and 1,619 women within 90 days of surgical repair of low-trauma hip fracture in the same study (for comparison).
Once-yearly intravenous (IV) ZOL 5 mg (n = 248) or placebo (n = 260), loading dose of vitamin D, daily calcium, and vitamin D supplements.
Changes in BMD.
Percentage change from baseline in total hip BMD at Months 12 and 24 was significantly higher with ZOL than with placebo (between-group difference, 2.0%, P = .003, and 3.8%, P = .002, respectively). Percentage change from baseline in femoral neck BMD at Month 24 was significantly higher with ZOL than with placebo (3.8%, P = .003). The BMD benefit was comparable with that observed in women in this study. New clinical fractures occurred in 36 (7.1%) participants (ZOL, n = 16; placebo, n = 20; P = .64). The ZOL safety profile was comparable with that of placebo, with no significant differences in cardiovascular or long-term renal function and a trend toward lower mortality in ZOL-treated men.
Once-yearly IV ZOL 5 mg increases bone mass at the hip and femoral neck in men within 90 days of repair of a low-trauma hip fracture. Increases were of a similar magnitude to those observed in women in the same study.
Journal of the American Geriatrics Society 10/2011; 59(11):2084-90. · 3.74 Impact Factor
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ABSTRACT: Many studies have reported significant behavioral impact of physical activity interventions. However, few have examined changes in potential mediators of change preceding behavioral changes, resulting in a lack of information concerning how the intervention worked. Our purpose was to examine mediation effects of changes in psychosocial variables on changes in physical activity in type 2 diabetes patients.
Ninety-two patients (62 ± 9 years, 30, 0 ± 2.5 kg/m(2), 69% males) participated in a randomized controlled trial. The 24-week intervention was based on social-cognitive constructs and consisted of a face-to-face session, telephone follow-ups, and the use of a pedometer. Social-cognitive variables and physical activity (device-based and self-reported) were collected at baseline, after the 24-week intervention and at one year post-baseline. PA was measured by pedometer, accelerometer and questionnaire.
Post-intervention physical activity changes were mediated by coping with relapse, changes in social norm, and social modeling from family members (p ≤ 0.05). One-year physical activity changes were mediated by coping with relapse, changes in social support from family and self-efficacy towards physical activity barriers (p ≤ 0.05)
For patients with type 2 diabetes, initiatives to increase their physical activity could usefully focus on strategies for resuming regular patterns of activity, on engaging family social support and on building confidence about dealing with actual and perceived barriers to activity.
NCT00903500, ClinicalTrials.gov.
International Journal of Behavioral Nutrition and Physical Activity 09/2011; 8:105. · 3.83 Impact Factor
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ABSTRACT: Effectiveness of a behavioral modification program on physical activity (PA) and sedentary behavior in diabetes patients.
Ninety-two patients were randomly assigned to an intervention or control group. The 24-weeks intervention consisted of a face-to-face session, pedometer and seven telephone follow-ups. Mean selection criteria were 35-75 years; 25-35 kg/m(2); ≤ 12% HbA1c, treated for type 2 diabetes; no PA limitations. PA and sedentary behavior were measured by pedometer, accelerometer and questionnaire over the short- (24 weeks) and intermediate- (1 year) term.
The intervention group increased their steps/day by 2744, their total PA by 23 min/day (p<0.001) and decreased their sedentary behavior by 23 min/day (p<0.05) post-intervention. After 1 year the intervention group still had an increase of 1872 steps/day, 11 min/day total PA and a decrease of 12 min/day in sedentary behavior (p<0.001).
This pedometer-based behavioral modification program with telephone support showed lasting positive effects on steps/day, PA and sedentary behavior.
This study tested a convenient way to increase PA among type 2 diabetes patients.
Patient Education and Counseling 08/2011; 84(2):275-9. · 2.31 Impact Factor
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ABSTRACT: Orthopaedic surgeons frequently have to deal with osteoporotic fractures of the distal radius, hip and proximal humerus. Low bone mineral density is not only associated with an increased fracture risk but also with more fracture displacement and reduction loss. The specific problems and main treatment options for these fragility fractures are reviewed.
Acta orthopaedica Belgica 08/2011; 77(4):441-7. · 0.40 Impact Factor
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ABSTRACT: Although the number of iodine-deficient countries has been reduced by almost 50 % over the last decade, it still remains a frequently misunderstood health problem. The most devastating effects of iodine deficiency occur during fetal development and childhood, periods in which sufficient iodine delivery remains critical. Besides the determination of thyroid size, the concentration of urinary iodine, serum thyroid-stimulating hormone and serum thyroglobulin are useful biomarkers to assess iodine status. Severe iodine deficiency is associated with neurological complications, cretinism, endemic goitre development, hypothyroidism, decreased fertility and increased infant mortality. The recommended iodine supplementation strategies are based on correction of iodine deficiency, close monitoring and evaluation of iodine administration, cooperation of the salt industry, training of local health care professionals and education of the population. Besides the multiple beneficial effects of supplementation, we present in this review a critical look at the possible side effects.
The British journal of nutrition 07/2011; 106(7):964-73. · 3.45 Impact Factor
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ABSTRACT: Sex hormone-binding globulin (SHBG) modulates the bioavailability of sex steroids at tissue level. Genetic, hormonal and lifestyle-related factors determine the SHBG levels, and low SHBG levels are a known risk factor for the development of the metabolic syndrome, diabetes and cardiovascular diseases. We investigated to what extent different determinants contribute to the variation in SHBG levels in healthy young men.
Healthy male siblings (n = 677) aged 25-45 year were recruited in a cross-sectional, population-based study.
Lean and fat mass were measured using dual-energy X-ray absorptiometry (DXA), and immunoassays were used to determine the serum hormonal levels. Additional information about smoking and physical activity was obtained using questionnaires. Carriers of two SHBG polymorphisms, the Asp327Asn polymorphism and the (TAAAA)(n) repeat polymorphism, were identified.
Weight, BMI, whole body fat mass and truncal fat mass were negatively associated with SHBG levels. Body composition characteristics did not differ between SHBG genotype groups, indicating that body composition controls SHBG levels rather than the other way around. The associations may be mediated by adipokines because leptin and adiponectin were, respectively, inversely and positively associated with SHBG levels. Insulin and glucose were negatively associated with SHBG levels, as well as IGF-1 and IGF-BP3, while no associations were found with free thyroid hormone status.
In conclusion, we found that fat mass, insulin and IGF-1 levels are important negative determinants of SHBG levels in young healthy men. The association with fat mass could be mediated by the effects of adiponectin and/or leptin on SHBG synthesis.
Clinical Endocrinology 06/2011; 76(1):111-8. · 3.17 Impact Factor
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ABSTRACT: The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.
Calcified Tissue International 06/2011; 89(2):91-104. · 2.38 Impact Factor
