The Danish HD Registry-a nationwide family registry of HD families in Denmark.

The Danish Huntington's Disease Registry (DHR) is a nationwide family registry comprising 14 245 individuals from 445 Huntington's disease (HD) families of which the largest family includes 845 individuals in 8 generations. 1136 DNA and/or blood samples and 18 fibroblast cultures are stored in a local biobank. The birthplace of the oldest HD carrier in each of the 261 families of Danish origin was unevenly distributed across Denmark with a high number of families in the middle part of the peninsula Jutland and in Copenhagen, the capital. The prevalence of HD in Denmark was calculated to be 5-8:100 000. 1451 individuals in the DHR had the size of the HTT CAG repeat determined of which 975 had 36 CAG repeats or more (mean ± SD: 43,5 ± 4,8). Two unrelated individuals were compound heterozygous for alleles ≥36 CAGs, and 60 individuals from 34 independent families carried an intermediate allele.

Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men.

Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40-79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline. INTRODUCTION: This study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change. METHODS: Men aged 40-79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (ß-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later. RESULTS: Five hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (-0.04 %/year), bone mineral content (BMC) (-0.1 %/year) and cortical thickness (-0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (-0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters. CONCLUSIONS: Age-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.

Health economic aspects of vertebral augmentation procedures.

We reviewed all peer-reviewed papers analysing the cost-effectiveness of vertebroplasty and balloon kyphoplasty for osteoporotic vertebral compression fractures. In general, the procedures appear to be cost effective but are very dependent upon model input details. Better data, rather than new models, are needed to answer outstanding questions. Vertebral augmentation procedures (VAPs), including vertebroplasty (VP) and balloon kyphoplasty (BKP), seek to stabilise fractured vertebral bodies and reduce pain. The aim of this paper is to review current literature on the cost-effectiveness of VAPs as well as to discuss the challenges for economic evaluation in this research area. A systematic literature search was conducted to identify existing published studies on the cost-effectiveness of VAPs in patients with osteoporosis. Only peer-reviewed published articles that fulfilled the criteria of being regarded as full economic evaluations including both morbidity and mortality in the outcome measure in the form of quality-adjusted life years (QALYs) were included. The search identified 949 studies, of which four (0.4 %) were identified as relevant with one study added later. The reviewed studies differed widely in terms of study design, modelling framework and data used, yielding different results and conclusions regarding the cost-effectiveness of VAPs. Three out of five studies indicated in the base case results that VAPs were cost effective compared to non-surgical management (NSM). The five main factors that drove the variations in the cost-effectiveness between the studies were time horizon, quality of life effect of treatment, offset time of the treatment effect, reduced number of bed days associated with VAPs and mortality benefit with treatment. The cost-effectiveness of VAPs is uncertain. In answering the remaining questions, new cost-effectiveness analysis will yield limited benefit. Rather, studies that can reduce the uncertainty in the underlying data, especially regarding the long-term clinical outcomes of VAPs, should be conducted.

Bone turnover markers predict hip bone loss in elderly European men: results of the European Male Ageing Study (EMAS).

SUMMARY: The aim of this study was to determine whether bone turnover markers (BTMs) predict changes in areal bone mineral density (aBMD) in middle-aged and elderly European men. Older men with high bone turnover are at a higher risk of accelerated hip bone loss, but the clinical utility of BTMs in individuals is limited. INTRODUCTION: Prospective studies on the value of BTMs to predict changes in aBMD in men are few and conflicting. The aim of this study was to determine whether BTMs predict changes in aBMD in middle-aged and elderly European men. METHODS: In 487 men aged 40-79 years from the European Male Ageing Study (EMAS), BTMs were assessed at baseline and dual-energy X-ray absorptiometry (DXA) at the lumbar spine (LS), femoral neck (FN) and total hip (TH) was performed at baseline and after a mean follow-up of 4.3 years. RESULTS: The mean aBMD decreased by 0.32%/year at FN and 0.22%/year at TH and increased by 0.32%/year at LS. Higher baseline levels of ß C-terminal cross-linked telopeptide (ß-CTX) and N-terminal propeptide of type I procollagen (PINP) were significantly associated with higher loss of hip aBMD in the whole cohort and men aged 60-79 years. These associations remained significant after adjustment for age, centre and body mass index (BMI). Men aged 60-79 years with ß-CTX in the upper quintile were more likely of being in the upper quintile of annual percentage (%) aBMD loss at FN (OR=4.27; 95% CI=2.09-8.73) and TH (OR=3.73; 95% CI=1.84-7.57). The positive predictive value (PPV) was 46% at both hip sites. CONCLUSION: Older men with high bone turnover have a higher risk of accelerated hip bone loss, but the PPV is low. BTMs are therefore unlikely to be of clinical utility in predicting accelerated hip bone loss in individual subjects.

Management of osteoporosis of the oldest old.

UNLABELLED: 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. INTRODUCTION: This consensus article reviews the therapeutic strategies and management options for the treatment of osteoporosis of the oldest old. This vulnerable segment (persons over 80 years of age) stands to gain substantially from effective anti-osteoporosis treatment, but the under-prescription of these treatments is frequent. METHODS: This report is the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores some of the reasons for this and presents the arguments to counter these beliefs. The risk assessment of older individuals is briefly reviewed along with the differences between some intervention guidelines. The current evidence on the impact of nutritional deficiencies (i.e. calcium, protein and vitamin D) is presented, as are strategies to prevent falls. One possible reason for the under-prescription of pharmacological treatments for osteoporosis in the oldest old is the perception that anti-fracture efficacy requires long-term treatment. However, a review of the data shows convincing anti-fracture efficacy already by 12 months. RESULTS: The safety profiles of these pharmacological agents are generally satisfactory in this patient segment provided a few precautions are followed. CONCLUSION: These patients should be considered for particular consultation/follow-up procedures in the effort to convince on the benefits of treatment and to allay fears of adverse drug reactions, since poor adherence is a major problem for the success of a strategy for osteoporosis and limits cost-effectiveness.

Late-onset hypogonadism and mortality in aging men.

CONTEXT: Late-onset hypogonadism (LOH) has recently been defined as a syndrome in middle-aged and elderly men reporting sexual symptoms in the presence of low T. The natural history of LOH, especially its relationship to mortality, is currently unknown. OBJECTIVE: The aim of this study was to clarify the associations between LOH, low T, and sexual symptoms with mortality in men. DESIGN, SETTING, AND PARTICIPANTS: Prospective data from the European Male Aging Study (EMAS) on 2599 community-dwelling men aged 40-79 years in eight European countries was used for this study. MAIN OUTCOME MEASURE(S): All-cause, cardiovascular, and cancer-related mortality was measured. RESULTS: One hundred forty-seven men died during a median follow-up of 4.3 years. Fifty-five men (2.1%) were identified as having LOH (31 moderate and 24 severe). After adjusting for age, center, body mass index (BMI), current smoking, and poor general health, compared with men without LOH, those with severe LOH had a 5-fold [hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.7, 11.4] higher risk of all-cause mortality. Compared with eugonadal men, the multivariable-adjusted risk of mortality was 2-fold higher in those with T less than 8 nmol/L (irrespective of symptoms; HR 2.3; 95% CI 1.2, 4.2) and 3-fold higher in those with three sexual symptoms (irrespective of serum T; compared with asymptomatic men; HR 3.2; 95% CI 1.8, 5.8). Similar risks were observed for cardiovascular mortality. CONCLUSIONS: Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the level of T and the presence of sexual symptoms contribute independently. Detecting low T in men presenting with sexual symptoms offers an opportunity to identify a small subgroup of aging men at particularly high risk of dying.

Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study.

UNLABELLED: 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.

Ergotamine-induced pleural and pericardial effusion successfully treated with colchicine.

A 83-year-old woman was admitted to hospital with chest pain, fever, dry cough and palpitations. Chest X-ray revealed a pleural effusion, assumed to be caused by cardiac failure and respiratory infection. Despite treatment with antibiotics and diuretics, the pleural effusion increased on chest X-ray and there were signs of pleural and pericardial effusion on computed tomography (CT) scan. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was not successful. Meanwhile patients' long-term use of ergotamine for migraine was revealed, which is associated with pleuropulmonary and cardiac fibrotic reactions. Tentative treatment with colchicine was successful, with complete resolution of pleural fluid, fever, cough and inflammatory parameters. This case highlights the importance of establishing an ergot alkaloid use registry in unexplained pleuropericardial effusions and supports the use of colchicine as a potential therapeutic approach.

Tools in the assessment of sarcopenia.

This review provides a framework for the development of an operational definition of sarcopenia and of the potential end points that might be adopted in clinical trials among older adults. While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate end points for determining outcomes of clinical importance which might be utilized in intervention studies. We review current approaches to the definition of sarcopenia and the methods used for the assessment of various aspects of physical function in older people. The potential end points of muscle mass, muscle strength, muscle power, and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these end points in clinical trials. Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomized clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area.

The transcription intermediary factor 1ß coactivates the androgen receptor.

The androgen receptor (AR) is a ligand-inducible transcription factor. Its transcription activation domain consists of the two transcription activation units called Tau-1 and Tau- 5. Tau-5 interacts with p160 coactivators like the transcription intermediary factor 2 (TIF2), which in their turn recruit histone modifiers and chromatin-remodelling complexes. The mechanism of action of Tau-1, however, remains elusive. Here, we demonstrate that transcription intermediary factor 1ß (TIF1ß) can induce the activity of the AR up to five fold when tested in vitro. Although there is no evidence for direct interactions between TIF1ß and AR, mutation studies show that the activity of TIF1ß depends on the integrity of Tau-1 in AR on the one hand, and the so-called tripartite motif domain in TIF1ß on the other. Surprisingly, the coactivation by TIF1ß via Tau-1 seems additive rather than cooperative with the AR coactivation by TIF2. Some mutations naturally occurring in androgen-insensitivity syndrome patients that reside in Tau-1 seem to impair the TIF1ß coactivation of the AR, indicating that TIF1ß could also be relevant for the in vivo androgen response in humans. Moreover, since TIF1ß is well expressed in prostate cancer cells, its functional interaction with androgen signalling could in the long run be a therapeutic target for this disease.

The impact of different health dimensions on overall quality of life related to kyphoplasty and non-surgical management.

UNLABELLED: This study uses data from a previously published randomised trial where balloon kyphoplasty was compared to non-surgical management. Of the improved overall quality of life, 60 % was caused by decreased pain. However, ignoring other dimensions of quality of life would underestimate the procedure's effect. INTRODUCTION: Acute back pain has been viewed as the most important factor lowering quality of life (QoL) for patients suffering vertebral fractures. The objective of this study was to quantify the impact of different health dimensions on overall QoL using patient-reported outcome measurements (PROMs) collected in Fracture Reduction Evaluation (FREE) trial. METHODS: The analysis was based on patients included in the 2-year-long randomised controlled FREE trial studying the efficacy and safety of balloon kyphoplasty procedure (BKP) compared to non-surgical management (NSM). The PROMs included were EQ-5D, Short Form (SF)-36, visual analogue scale (VAS) pain and the Roland-Morris Disability Questionnaire (RMDQ). The health dimensional contribution to the overall QoL improvements was analysed by isolating the impact of each dimension on QoL in the SF-36 and EQ-5D, respectively. A correlation analysis of the QoL improvement was performed to investigate the relationships between the four instruments. RESULTS: Changes in pain explained 60 % of the quality-adjusted life years (QALY) gained in BKP vs. NSM followed by self-care (17 %), mobility (16 %) and usual activities (10 %) (EQ-5D). Health dimensions capturing the mental state had little impact on the QALY gained. The SF-36 dimensional analysis showed similar results. The correlation analysis showed that the correlation between VAS pain, RMDQ and QALY improvement was fairly weak. CONCLUSIONS: Changes in the pain dimension of health are the most important drivers for changes of overall QoL in patients treated with BKP or NSM. However, ignoring the impact of other dimensions would lead to an underestimation of the actual improvement in overall QoL.

Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study.

OBJECTIVE: Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. DESIGN: A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (±S.D.) 4.4±0.3 years later. RESULTS: Paired testosterone results were available for 2395 men. Mean (±S.D.) annualised hormone changes were as follows: testosterone -0.1±0.95  nmol/l; free testosterone (FT) -3.83±16.8  pmol/l; sex hormone-binding globulin (SHBG) 0.56±2.5  nmol/l and LH 0.08±0.57  U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost ≥15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. CONCLUSIONS: Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction.

Reduction in the risk of clinical fractures after a single dose of zoledronic Acid 5 milligrams.

CONTEXT: Annual infusions of zoledronic acid 5 mg over 3 years have been shown to reduce fracture incidence. There is now evidence that the effects of a single dose of zoledronic acid on bone mineral density and bone turnover last for much more than a year. Whether this is associated with sustained fracture prevention is not known. OBJECTIVE: The objective of the study was to assess fracture incidence after only 1 infusion of zoledronic acid. DESIGN: The design of the study included post hoc analysis of subgroups of subjects from 2 trials, who received only 1 study infusion. SETTING: The study included multicenter, randomized controlled trials. PARTICIPANTS: A total of 1367 subjects from HORIZON-PFT and HORIZON-RFT studies who received only 1 of the planned annual infusions participated in the study. INTERVENTION: The intervention of the study consisted of 1 infusion of zoledronic acid or placebo. MAIN OUTCOME MEASURE: Clinical fracture was the main outcome measure of the study. RESULTS: Mean follow-up period was 1.5 years. In patients who received only a single infusion, there was a 32% reduction in clinical fracture comparing zoledronic acid with placebo over 3 years of follow-up (95% confidence interval 2-53%, P = .04), comparable with the fracture reduction seen in those who had 3 or more annual infusions (34%; 95% confidence interval, 23-43%, P < .0001). New morphometric vertebral fractures were reduced by 68% in the single-infusion group (P = .004). The between-group differences in total hip bone mineral density at 3 years were 3.8% in those receiving 1 infusion and 6.2% in those receiving 3 infusions. CONCLUSIONS: In this post hoc analysis based on postrandomization subgroups, fracture risk appears to be reduced for more than 1 year after a single infusion of zoledronic acid. Prospective studies designed to assess this possibility are now warranted.

Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

BACKGROUND: Vitamin D insufficiency has deleterious consequences on health outcomes. In elderly or postmenopausal women, it may exacerbate osteoporosis. SCOPE: There is currently no clear consensus on definitions of vitamin D insufficiency or minimal targets for vitamin D concentrations and proposed targets vary with the population. In view of the potential confusion for practitioners on when to treat and what to achieve, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) convened a meeting to provide recommendations for clinical practice, to ensure the optimal management of elderly and postmenopausal women with regard to vitamin D supplementation. FINDINGS: Vitamin D has both skeletal and extra-skeletal benefits. Patients with serum 25-hydroxyvitamin D (25-(OH)D) levels <50 nmol/L have increased bone turnover, bone loss, and possibly mineralization defects compared with patients with levels >50 nmol/L. Similar relationships have been reported for frailty, nonvertebral and hip fracture, and all-cause mortality, with poorer outcomes at <50 nmol/L. CONCLUSION: The ESCEO recommends that 50 nmol/L (i.e. 20 ng/mL) should be the minimal serum 25-(OH)D concentration at the population level and in patients with osteoporosis to ensure optimal bone health. Below this threshold, supplementation is recommended at 800 to 1000 IU/day. Vitamin D supplementation is safe up to 10,000 IU/day (upper limit of safety) resulting in an upper limit of adequacy of 125 nmol/L 25-(OH)D. Daily consumption of calcium- and vitamin-D-fortified food products (e.g. yoghurt or milk) can help improve vitamin D intake. Above the threshold of 50 nmol/L, there is no clear evidence for additional benefits of supplementation. On the other hand, in fragile elderly subjects who are at elevated risk for falls and fracture, the ESCEO recommends a minimal serum 25-(OH)D level of 75 nmol/L (i.e. 30 ng/mL), for the greatest impact on fracture.

Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men.

CONTEXT: Strontium ranelate reduces vertebral and nonvertebral fracture risk in postmenopausal osteoporosis. OBJECTIVE: The objective of this study was to determine the efficacy and safety of strontium ranelate in osteoporosis in men over 2 years (main analysis after 1 year). DESIGN: This was an international, unbalanced (2:1), double-blind, randomized placebo-controlled trial (MALEO [MALE Osteoporosis]). SETTING: This international study included 54 centers in 14 countries. PARTICIPANTS: PARTICIPANTS were 261 white men with primary osteoporosis. INTERVENTION: Strontium ranelate at 2 g/d (n = 174) or placebo (n = 87) was administered. MAIN OUTCOME MEASURES: Lumbar spine (L2-L4), femoral neck, and total hip bone mineral density (BMD), biochemical bone markers, and safety were measured. RESULTS: Baseline characteristics were similar in both groups in the whole population (age, 72.9 ± 6.0 years; lumbar spine BMD T-score, -2.7 ± 1.0; femoral neck BMD T-score, -2.3 ± 0.7). Men who received strontium ranelate over 2 years had greater increases in lumbar spine BMD than those who received placebo (relative change from baseline to end, 9.7% ± 7.5% vs 2.0% ± 5.5%; between-group difference estimate (SE), 7.7% (0.9%); 95% confidence interval, 5.9%-9.5%; P < .001). There were also significant between-group differences in relative changes in femoral neck BMD (P < .001) and total hip BMD (P < .001). At the end of treatment, mean levels of serum cross-linked telopeptides of type I collagen, a marker of bone resorption, were increased in both the strontium ranelate group (10.7% ± 58.0%; P = .022) and the placebo group (34.9% ± 65.8%; P < .001). The corresponding mean changes of bone alkaline phosphatase, a marker of bone formation, were 6.4% ± 28.5% (P = .005) and 1.9% ± 25.4% (P = .505), respectively. After 2 years, the blood strontium level (129 ± 66 µmol/L) was similar to that in trials of postmenopausal osteoporosis. Strontium ranelate was generally well tolerated. CONCLUSIONS: The effects of strontium ranelate on BMD in osteoporotic men were similar to those in postmenopausal osteoporotic women, supporting its use in the treatment of osteoporosis in men.

Frailty Is Associated with Impaired Quality of Life and Falls in Middle-Aged and Older European Men.

OBJECTIVES: Adapt a measure of frailty for use in a cohort study of European men and explore relationships with age, health related quality of life and falls. DESIGN: Longitudinal cohort study. SETTING: 8 European centers. PARTICIPANTS: 3047 men aged 40-79 participating in the European Male Ageing Study (EMAS). MEASUREMENTS: Frailty was assessed using an adaptation of the Cardiovascular Health Study criteria. Health related quality of life was evaluated using the Rand Short Form-36 (SF-36) questionnaire which comprises both mental and physical component scores. Self reported falls in the preceding 12 months were recorded at 2-year follow-up. RESULTS: 78 men (2.6%) were classified as frail (≥3 criteria) and 821 (26.9%) as prefrail (1-2 criteria). The prevalence of frailty increased from 0.1% in men aged 40-49 up to 6.8% in men aged 70-79. Compared to robust men, both prefrail and frail men had lower health related quality of life. Frailty was more strongly associated with the physical than mental subscales of the SF-36. Frailty was associated with higher risk of falls OR (95% CI) 2.92 (1.52, 5.59). CONCLUSIONS: Frailty, assessed by the EMAS criteria, increased in prevalence with age and was related to poorer health related quality of life and higher risk of falls in middle-aged and older European men. These criteria may help to identify a vulnerable subset of older men.

Epidemiological evidence against a role for C-reactive protein causing leptin resistance.

OBJECTIVE: It has been suggested that elevated levels of C-reactive protein (CRP) might interfere with leptin signalling and contribute to leptin resistance. Our aim was to assess whether plasma levels of CRP influence leptin resistance in humans, and our hypothesis was that CRP levels would modify the cross-sectional relationships between leptin and measures of adiposity. DESIGN AND METHODS: W assessed four measures of adiposity: BMI, waist circumference, fat mass and body fat (%) in 2113 British Regional Heart Study (BRHS) men (mean (s.d.) age 69 (5) years), with replication in 760 (age 69 (6) years) European Male Ageing Study (EMAS) subjects. RESULTS: IN BRHS subjects, leptin correlated with CRP (SPEARMAN'S R=0.22, P0.0001). Leptin and crp correlated with all four measures of adiposity (R VALUE RANGE: 0.22-0.57, all P<0.0001). Age-adjusted mean levels for adiposity measures increased in relation to leptin levels, but CRP level did not consistently influence the ß-coefficients of the regression lines in a CRP-stratified analysis. In BRHS subjects, the BMI vs leptin relationship demonstrated a weak statistical interaction with CRP (P=0.04). We observed no similar interaction in EMAS subjects and no significant interactions with other measures of adiposity in BRHS or EMAS cohorts. CONCLUSION: We have shown that plasma CRP has little influence on the relationship between measures of adiposity and serum leptin levels in these middle-aged and elderly male European cohorts. This study provides epidemiological evidence against CRP having a significant role in causing leptin resistance.

Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men.

UNLABELLED: The aim of this study was to determine the relationship between reduced muscle mass (sarcopenia) and areal bone mineral density (BMD(a)) in middle-aged and elderly community-dwelling European men. Men with sarcopenia had significantly lower BMD(a) and were more likely to have osteoporosis compared with men without sarcopenia. INTRODUCTION: In men, the relationship between reduced muscle mass (sarcopenia) and BMD(a) is unclear. This study aimed to determine this relationship in middle-aged and elderly community-dwelling men. METHODS: Men aged 40-79 years from the Manchester (UK) and Leuven (Belgium) cohorts of the European Male Ageing Study were invited to attend for assessment including dual-energy X-ray absorptiometry, from which appendicular lean mass (aLM), fat mass (FM) and whole-body, spine and hip BMD(a) were determined. Relative appendicular skeletal muscle mass (RASM) was calculated as aLM/height². Muscle strength was assessed in subjects from Leuven. Sarcopenia was defined by RASM at <7.26 kg/m² and by the recent definition of the European Working Group on Sarcopenia in Older People (RASM at <7.26 kg/m(2) plus low muscle function). Linear regression was used to determine the associations between aLM, FM, muscle strength and BMD(a) and logistic regression to determine the association between sarcopenia and osteoporosis. RESULTS: Six hundred seventy-nine men with a mean age of 59.6 (SD = 10.7), contributed data to the analysis; 11.9 % were sarcopenic by the conventional definition. After adjustment for age and centre, aLM, RASM and FM were positively associated with BMD(a). Men with RASM at <7.26 kg/m² had significantly lower BMD(a) compared with those with RASM at ≥7.26 kg/m(2). In a multivariable model, aLM was most consistently associated with BMD(a). Men with sarcopenia were more likely to have osteoporosis compared with those with normal RASM (odds ratio = 3.0; 95 % CI = 1.6-5.8). CONCLUSIONS: Sarcopenia is associated with low BMD(a) and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis.

Non-hip, non-spine fractures drive healthcare utilization following a fracture: the Global Longitudinal Study of Osteoporosis in Women (GLOW).

UNLABELLED: We evaluated healthcare utilization associated with treating fracture types in >51,000 women aged ≥55 years. Over the course of 1 year, there were five times more non-hip, non-spine fractures than hip or spine fractures, resulting in twice as many days of hospitalization and rehabilitation/nursing home care for non-hip, non-spine fractures. INTRODUCTION: The purpose of this study is to evaluate medical healthcare utilization associated with treating several types of fractures in women ≥55 years from various geographic regions. METHODS: Information from the Global Longitudinal Study of Osteoporosis in Women (GLOW) was collected via self-administered patient questionnaires at baseline and year 1 (n = 51,491). Self-reported clinically recognized low-trauma fractures at year 1 were classified as incident spine, hip, wrist/hand, arm/shoulder, pelvis, rib, leg, and other fractures. Healthcare utilization data were self-reported and included whether the fracture was treated at a doctor's office/clinic or at a hospital. Patients were asked if they had undergone surgery or been treated at a rehabilitation center or nursing home. RESULTS: During 1-year follow-up, there were 195 spine, 134 hip, and 1,654 non-hip, non-spine fractures. Clinical vertebral fractures resulted in 617 days of hospitalization and 512 days of rehabilitation/nursing home care; hip fractures accounted for 1,306 days of hospitalization and 1,650 days of rehabilitation/nursing home care. Non-hip, non-spine fractures resulted in 3,805 days in hospital and 5,186 days of rehabilitation/nursing home care. CONCLUSIONS: While hip and vertebral fractures are well recognized for their associated increase in health resource utilization, non-hip, non-spine fractures, by virtue of their 5-fold greater number, require significantly more healthcare resources.