Introducing mobile fracture prevention services with DXA in Northern Scotland: a comparative study of three rural communities.

Mobile fracture prevention services, with DXA, significantly improved access to care for those at high risk of fracture living in rural areas. Introduction of mobile services facilitated access to fracture liaison services and development of integrated of care pathways across community- and secondary-based care. INTRODUCTION: The ageing population is growing faster in rural areas, yet most fracture prevention services are located in urban areas. As part of a wider study, evaluating the introduction of mobile fracture prevention services, we focus on whether mobile services improve access to care for those at highest risk of fracture. METHODS: Services outcomes were assessed against the Royal Osteoporosis Society clinical standards for fracture liaison services. This included standardised, age-specific referral rates, FRAX 10-year probability of major osteoporotic and hip fracture of referrals, pre- and post-introduction of the mobile service across two island and one rural mainland sites. This was compared with referrals from a similar rural mainland region with local access to a comprehensive service. RESULTS: Greatest impact occurred in areas with most limited service provision at baseline. Mean age of patients referred increased from 59 to 68 years (CI 6.8-10.1, p < 0.001). Referral rates increased from 2.8 to 5.4 per 1000 population between 2011 and 2018, with a 5-fold rise in those ≥ 75 years (0.4 to 2.0 per 1000). Mean FRAX 10-year risk of major osteoporotic fracture increased from 12.7 to 17.7% (CI 3.2-5.7, p < 0.001). Mean hip fracture risk probability increased from 3.0 to 5.7% (CI 2.0-3.4, p < 0.001). However, referral rates from the mobile sites remained lower than the comparator site. CONCLUSIONS: Mobile fracture prevention services, including DXA, greatly improved uptake amongst high-risk individuals. Mobile services facilitated development of integrated of care pathways, including fracture liaison services, across community- and secondary-based care.

Significant morphological change in osteoarthritic hips identified over 6-12 months using statistical shape modelling.

OBJECTIVE: Predicting who will develop osteoarthritis, assessing how rapidly their disease will progress and monitoring early responses to treatment are key to the development of therapeutic agents able to treat this crippling disease and to their future clinical use. Statistical Shape Modelling (SSM) enables quantification of variations in multiple geometric measures describing the whole hip joint to be considered in concert. This prospective study evaluates the responsiveness of SSM to changes in hip-shape within 1 year. METHODS: Sixty-two people, mean age 67.1 yrs, were recruited. Dual-energy X-ray Absorptiometry images were taken at three timepoints (baseline, 6 and 12 months). Based on Kellgren-Lawrence grading (KLG) of their baseline images, subjects were classified into control/doubtful OA: KLG < 1 in both hips; moderate OA: KLG = 2; and severe OA: KLG ≥ 3 in their most severe hip. Morphology was quantified using SSM and changes in shape were assessed using generalised estimating equations. Standardized response means (SRMs) were calculated for the first and second 6 month periods, then the full 12 months. RESULTS: Disease severity ranged from KLG0-KLG4 in the 124 hips assessed at baseline. Three SSM modes (Modes 1, 3 and 4) were associated with OA severity. Across the whole cohort, SRM magnitudes ranged from 0.16 to 0.63. The greatest subgroup SRM (magnitude 0.91) was observed over 12 months in those subjects with moderate OA (KLG2). CONCLUSIONS: We have demonstrated that SSM can capture changes in hip shape over 6 and 12 months across the entire hip joint providing a sensitive measure of hip OA progression.

FRAX-based assessment and intervention thresholds--an exploration of thresholds in women aged 50 years and older in the UK.

UNLABELLED: Under current guidelines, based on prior fracture probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold (a fixed threshold from the age of 70 years) reduces this disparity, increases treatment access and decreases the need for bone densitometry. INTRODUCTION: Several international guidelines set age-specific intervention thresholds at the 10-year probability of fracture equivalent to a woman of average BMI with a prior fracture. At older ages (≥70 years), women with prior fracture selected for treatment are at lower average absolute risk than those selected for treatment in the absence of prior fracture, prompting consideration of alternative thresholds in this age group. METHODS: Using a simulated population of 50,633 women aged 50-90 years in the UK, with a distribution of risk factors similar to that in the European FRAX derivation cohorts and a UK-matched age distribution, the current NOGG intervention and assessment thresholds were compared to one where the thresholds remained constant from 70 years upwards. RESULTS: Under current thresholds, 45.1% of women aged ≥70 years would be eligible for therapy, comprising 37.5% with prior fracture, 2.2% with high risk but no prior fracture and 5.4% selected for treatment after bone mineral density (BMD) measurement. Mean hip fracture probability was 11.3, 23.3 and 17.6%, respectively, in these groups. Under the alternative thresholds, the overall proportion of women treated increased from 45.1 to 52.9%, with 8.4% at high risk but no prior fracture and 7.0% selected for treatment after BMD measurement. In the latter group, the mean probability of hip fracture was identical to that observed in women with prior fracture (11.3%). The alternative threshold also reduced the need for BMD measurement, particularly at older ages (>80 years). CONCLUSIONS: The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages.

Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

UNLABELLED: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. INTRODUCTION: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. METHODS: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. RESULTS: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. CONCLUSIONS: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

A parallel group double-blind RCT of vitamin D3 assessing physical function: is the biochemical response to treatment affected by overweight and obesity?

UNLABELLED: Vitamin D may affect skeletal muscle function. In a double-blind, randomised, placebo-controlled trial, we found that vitamin D3 supplementation (400 or 1,000 I.U. vs. placebo daily for 1 year with bimonthly study visits) does not improve grip strength or reduce falls. INTRODUCTION: This study aimed to test the supplementation effects of vitamin D3 on physical function and examine associations between overweight/obesity and the biochemical response to treatment. METHODS: In a parallel group double-blind RCT, healthy postmenopausal women from North East Scotland (latitude-57° N) aged 60-70 years (body mass index (BMI), 18-45 kg/m(2)) were assigned (computer randomisation) to daily vitamin D3 (400 I.U. (n = 102)/1,000 I.U. (n = 101)) or matching placebo (n = 102) (97, 96 and 100 participants analysed for outcomes, respectively) from identical coded containers for 1 year. Grip strength (primary outcome), falls, diet, physical activity and ultraviolet B radiation exposure were measured bimonthly, as were serum 25(OH)D, adjusted calcium (ACa) and phosphate. Fat/lean mass (dual energy X-ray absorptiometry), anthropometry, 1,25-dihydroxyvitamin D and parathyroid hormone were measured at baseline and 12 months. Participants and researchers were blinded throughout intervention and analysis. RESULTS: Treatment had no effect on grip strength (mean change (SD)/year = -0.5 (2.5), -0.9 (2.7) and -0.4 (3.3) kg force for 400/1,000 I.U. vitamin D3 and placebo groups, respectively (P = .10, ANOVA)) or falls (P = .65, chi-squared test). Biochemical responses were similar across BMI categories (<25.25-29.99, ≥30 kg/m(2)) with the exception of a small change at 12-months in serum ACa in overweight compared to non-overweight participants (P = .01, ANOVA; 1,000 I.U. group). In the placebo group, 25(OH)D peak concentration change (winter to summer) was negatively associated with weight (r = -.268), BMI (r = -.198), total (r = -.278) and trunk fat mass (r = -.251), with total and trunk fat mass predictive of winter to summer 25(OH)D change (P = .01/.004 respectively, linear regression). CONCLUSION: We found no evidence of an improvement in physical function following vitamin D3 supplementation for 1 year.

Impact of femoral neck and lumbar spine BMD discordances on FRAX probabilities in women: a meta-analysis of international cohorts.

There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. We studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS-FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculated using FN BMD. To examine the effect of an adjustment for ΔLS-FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in the highest third of each cohort. The absolute ΔLS-FN was greater than 2 SD for 2.5% of women and between 1 and 2 SD for 21%. ΔLS-FN was associated with a significant risk of fracture adjusted for baseline FRAX (HR per SD change = 1.09; 95% CI = 1.04-1.15). In reclassification analyses, only 2.3-3.2% of the women moved to a higher or lower risk category when using FRAX with ΔLS-FN compared with FN-derived FRAX alone. Adjustment of estimated fracture risk for a large LS/FN discrepancy (>2SD) impacts to a large extent on only a relatively small number of individuals. More moderate (1-2SD) discordances in FN and LS T-scores have a small impact on FRAX probabilities. This might still improve clinical decision-making, particularly in women with probabilities close to an intervention threshold.

Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and increased fracture risk. Current evidence suggests that the inheritance of bone mass is under polygenic control but the genes responsible are poorly defined. Type I collagen is the major protein of bone encoded by the COLIA1 and COLIA2 genes. While these are strong candidates for the genetic regulation of bone mass, no abnormality of either gene has so far been defined in osteoporosis. In this study, we describe a novel G-->T polymorphism in a regulatory region of COLIA1 at a recognition site for the transcription factor Sp1(7) that is significantly related to bone mass and osteoporotic fracture. G/T heterozygotes at the polymorphic Sp1 site (Ss) had significantly lower bone mineral density (BMD) than G/G homozygotes (SS) in two populations of British women and BMD was lower still in T/T homozygotes (ss). The unfavourable Ss and ss genotypes were over-represented in patients with severe osteoporosis and vertebral fractures (54%), as compared with controls (27%), equivalent to a relative risk of 2.97 (95% confidence interval 1.63-9.56) for vertebral fracture in individuals who carry the 's' allele. While the mechanisms that underlie this association remain to be defined, the COLIA1 Sp1 polymorphism appears to be an important marker for low bone mass and vertebral fracture, raising the possibility that genotyping at this site may be of value in identifying women who are at risk of osteoporosis.

Prevalence of non-fracture short vertebral height is similar in premenopausal and postmenopausal women: the osteoporosis and ultrasound study.

UNLABELLED: We observed similar prevalence of short vertebral height without endplate depression (SVH) in young women aged 20-39 years and older women aged 55-79 years. There was no association between SVH and low bone density. In older women, therefore, SVH may be largely long standing and not indicative of osteoporotic fracture. INTRODUCTION: Algorithm-based qualitative (ABQ) definition of osteoporotic vertebral fracture (VF) requires evidence of endplate fracture, and there is no minimum threshold for apparent 'reduction' in vertebral height. In older women, SVH without endplate fracture identified on baseline assessment may be long standing and unrelated to VF. If this is so, we would expect to see a similar prevalence of SVH in younger women. We aimed to compare the prevalence of pre- and postmenopausal women with SVH and the characteristics of women with and without SVH. METHODS: We used the ABQ method to classify baseline vertebral images (DXA-based imaging) from 257 premenopausal and 1,361 postmenopausal women participating in the population-based Osteoporosis and Ultrasound Study. Images were classified as follows: normal (no VF, no SVH), SVH (no VF) or VF (with/without SVH in unfractured vertebrae). We compared proportions of women with SVH (chi-squared test) and compared age, height, weight and bone mineral density (BMD) by ABQ classification (two-sample t test/analysis of variance). RESULTS: The prevalence of pre- and postmenopausal women with SVH was 37% and 33%, respectively (P>0.05). Compared to women without SVH, premenopausal women with SVH were older (P<0.001) and heavier (P=0.05), and postmenopausal women with SVH were taller (P<0.05), with higher spine BMD (P<0.01). Postmenopausal women with VF were older (P<0.001) and shorter (P<0.01) with lower BMD (P<0.001) than women without VF. CONCLUSIONS: Short vertebral height without endplate fracture is equally prevalent in pre- and postmenopausal women and not associated with low bone density.

A European multicenter comparison of quantitative ultrasound measurement variables: the OPUS study.

UNLABELLED: Quantitative ultrasound (QUS) measurement variables vary between European countries in a different way to hip bone mineral density. Standardization of data can be achieved through statistical approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied. INTRODUCTION: European between-center differences in hip bone mineral density (BMD) have been shown to exist; however, little is known about the geographical heterogeneity of QUS measurement variables. We aimed to examine the differences in QUS variables between three different European countries. METHODS: Five calcaneal and phalangeal QUS devices in Sheffield, Aberdeen (UK), Kiel and Berlin (Germany), and three devices in Paris (France) were used to measure QUS variables in younger (n = 463, 20-39 years old) and older (n = 2,399, 55-79 years old) women participating in the European multicenter Osteoporosis and Ultrasound (OPUS) study. Broadband ultrasound attenuation, speed of sound, stiffness index, amplitude-dependent speed of sound, bone transmission time, and ultrasonic bone profiler index data were collected. Between-center differences were examined using ANOVA followed by post hoc Fisher's least significant difference tests, and ANCOVA with linear contrasts. p < 0.05 indicated statistical significance. RESULTS: Between-center differences in nonstandardized QUS measurement variables existed for younger (p = 0.0023 to p < 0.0001) and older women (p < 0.001). Anthropometric characteristics exerted a significant influence on nonstandardized data (p = 0.045 to p < 0.001). However, following statistical standardization, based on height and weight or based on measurements made in young people, geographical heterogeneity in QUS measurement variables was no longer apparent. CONCLUSIONS: QUS measurement variables vary between European countries in a different way to those for hip BMD. Standardization of data can be achieved through statistical approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied.

Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis.

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤ 3 months) subpopulations]were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤ 74 years (P<0.05) in the treatment and 65-74 years (P = 0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P<0.05), cumulative prednisone dose (all P<0.01), and postmenopausal status (all P<0.05). In premenopausal women, in both subpopulations, zoledronic acid significantly increased total hip BMD (all P<0.05) versus risedronate at month 12 but not LS BMD. Osteoporotic patients in the prevention (P=0.0189) and osteopenic patients in the treatment subpopulation (P=0.0305) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12. Conclusions This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients.

Endogenous estradiol and the risk of incident fracture in postmenopausal women: the OPUS study.

Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study. Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for all subjects at baseline and 6-year follow-up. Nonfasting blood samples were taken at baseline for E(2), SHBG, DHEAS, and bone turnover markers. Incident nonvertebral fractures were self-reported and verified; vertebral fractures were diagnosed at a single center from spinal radiographs. Medical and lifestyle data were obtained by questionnaire at each visit. Thirty-nine subjects had an incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the lowest quartile predicted vertebral fracture independent of confounders including age, body mass index, bone mineral density, bone turnover, fracture history, and use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI] 1.52-5.82) by logistic regression. A calculated free estradiol index was not a stronger predictor than total E(2). Higher SHBG predicted vertebral fracture independently of age and body mass index, but not independently of E(2), bone mineral density, or prevalent fracture. Low DHEAS did not predict vertebral fracture. Nonvertebral fractures were not predicted by any of E(2), SHBG, or DHEAS, either in univariate or multivariate analyses. These findings suggest that there may be mechanistic differences in the protective effect of E(2) at vertebral compared with nonvertebral sites.

International variation in proximal femur bone mineral density.

UNLABELLED: We observed higher proximal femur bone mineral density (BMD) in European women compared to average values derived from US Caucasian women in the National Health and Nutrition Examination Survey (NHANES) study. Across European centres, Parisian women had lower proximal femur BMD compared to women from Kiel or Sheffield. INTRODUCTION: Proximal femur BMD of US adults (NHANES III) may not accurately reflect that of European women. We examined the heterogeneity of BMD across European and US Caucasian women and across different European populations. METHODS: Proximal femur BMD was measured in women ages 20-39 years (n=258) and 55-79 years (n=1,426) from three European centres. Cross-calibrated BMD for total hip, femoral neck, trochanter and intertrochanter were examined. International variation in BMD was assessed by comparing means and SDs in the European data with those from the US NHANES III study. European populations were stratified into 5-year age bands to establish individual centre reference intervals. Between-centre differences were assessed using ANOVA and post hoc Fisher's least significant difference tests. RESULTS: European women had higher BMD than US women: The differences were 7.1% to 14.2% (p<0.001) and 0% to 3.9% (p<0.05) in the older and younger women, respectively. Standard deviations for BMD at the different sites were comparable to those for US women. Among older, but not younger European women, proximal femur BMD was significantly lower in French women (Paris) than in women from Germany (Kiel) or the UK (Sheffield) (difference=5.0% to 9.6%, p<0.05). CONCLUSIONS: International variation in hip BMD does exist, with international and between-centre differences being less evident at the femoral neck.

Sunlight and dietary contributions to the seasonal vitamin D status of cohorts of healthy postmenopausal women living at northerly latitudes: a major cause for concern?

UNLABELLED: We assessed sunlight and dietary contributions to vitamin D status in British postmenopausal women. Our true longitudinal 25-hydroxyvitamin D (25(OH)D) measurements varied seasonally, being lower in the north compared to the south and lower in Asian women. Sunlight exposure in summer and spring provided 80% total annual intake of vitamin D. INTRODUCTION: Vitamin D deficiency is highlighted as a potential problem for countries at high latitude, but there are few true longitudinal, seasonal data to allow regional comparisons. We aimed to directly compare seasonal variation in vitamin D status (25(OH)D) in postmenopausal women at two northerly latitudes and to assess the relative contributions of sunlight exposure and diet. METHODS: Vitamin D status was assessed in 518 postmenopausal women (age 55-70 years) in a two-centre cohort study with serum collected at fixed three-monthly intervals from summer 2006 for immunoassay measurement of 25(OH)D and parathyroid hormone. At 57° N (Aberdeen, Scotland, UK), there were 338 Caucasian women; at 51° N (Surrey, South of England, UK), there were 144 Caucasian women and 35 Asian women. UVB exposure (polysulphone film badges) and dietary vitamin D intakes (food diaries) were also estimated. RESULTS: Caucasian women had lower 25(OH)D (p < 0.001) at 57° N compared to 51° N. Median (interquartile range) in nanomoles per litre for summer (June-August) at 57° N was 43.0 (20.9) and at 51° N was 62.5 (26.6) and for winter (December-February) at 57° N was 28.3 (18.9) and at 51° N was 39.9 (24.0). For Asian women at 51° N, median 25(OH)D was 24.0 (15.8) nmol/L in summer and 16.9 (15.9) nmol/L in winter. Median dietary vitamin D intakes were 80-100 IU for Caucasians and 50-65 IU for the Asian women. Sunlight was the main contributor to 25(OH)D with spring and summer providing >80% total annual intake. CONCLUSIONS: These longitudinal data show significant regional and ethnic differences in UVB exposure and vitamin D status for postmenopausal women at northerly latitudes. The numbers of women who are vitamin D deficient is a major concern and public health problem.

Population screening for osteoporosis risk: a randomised control trial of medication use and fracture risk.

UNLABELLED: Randomised control trial of osteoporosis screening in 4,800 women aged 45-54 years was carried out. Screened group observed an increase of 7.9% in hormone replacement therapy (HRT) use (p < 0.001), 15% in other osteoporosis treatments (p < 0.001) and a 25.9% reduction in fracture risk compared with control. Screening for osteoporosis significantly increases treatment use and reduces fracture incidence. INTRODUCTION: Population screening programmes can identify menopausal women with low bone mineral density (BMD) and elevated risk of future fracture but require to be proven effective by a randomised control trial. METHODS: A total of 4,800 women, 45-54 years, were randomised in equal numbers to screening or no screening (control) groups. Following screening, those in the lowest quartile of BMD were advised to consider HRT. Nine years later, the effect of screening on the uptake of treatment and the incidence of fractures were assessed by postal questionnaire. Categorical differences were assessed using chi(2) test. Cox regression was used to assess hazard ratio (HR). RESULTS: Of the screened and the control groups, 52.4% vs 44.5%, respectively, reported taking HRT (p < 0.001). In addition, 36.6% of the screened vs 21.6% of the control groups reported the use of vitamin D, calcium, alendronate, etidronate or raloxifene (p < 0.001). In a per protocol analysis of verified incident fractures, a 25.9% reduction in risk of fractures (of any site) in the screened group was observed (HR = 0.741, 95% CI = 0.551-0.998 adjusted age, weight and height). CONCLUSIONS: Screening for osteoporosis as assessed by low bone density significantly increases the use of HRT and other treatments for osteoporosis and reduces fracture incidence.

Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS).

SUMMARY: Fall prevention is a key strategy for reducing osteoporotic fractures. We investigated the association between vitamin D receptor (VDR) polymorphisms and reported falls in postmenopausal women. Bsm1 polymorphisms were associated with falls, balance and muscle power measurements. These results may explain some of the excess fracture risk associated with VDR in some studies. INTRODUCTION: Fall prevention is a key strategy for reducing osteoporotic fractures. It has been suggested that vitamin D supplementation may reduce the incidence of falls by reducing body sway and increasing muscle power. The vitamin D receptor gene is a well-studied candidate gene for osteoporosis. We investigated the association between VDR polymorphisms and reported falls in postmenopausal women. METHODS: Falls data were collected in two separate population cohorts. Five polymorphisms of the VDR gene were analysed (Cdx-2, Fok-1, BsmI, Taq1 and Apa1) in the Aberdeen Prospective Osteoporosis Screening Study (APOSS) cohort. Results found in APOSS were then validated in an independent cohort--the Osteoporosis and Ultrasound (OPUS) study (Bsm1 and Fok1 only), where muscle power and balance were also measured. RESULTS: Carriers of the 'B' allele (Bsm1) showed an increased risk for falls. In APOSS, this was statistically significant for visit 3 multiple falls (p = 0.047) and for recurrent falls (p = 0.043). Similar results were found in OPUS for visit 1 falls (p = 0.025) and visit 1 multiple falls (p = 0.015). Bsm1 polymorphisms were also associated with balance and muscle power measurements. CONCLUSIONS: In conclusion, these results demonstrate an association between the Bsm1 polymorphism and risk of falling that may explain some of the excess fracture risk associated with VDR in some studies.

Physical activity and dietary calcium interactions in bone mass in Scottish postmenopausal women.

UNLABELLED: In this population-based cohort of 1,254 older Scottish women we found significant interactions between the mechanical component of self-reported habitual physical activity (PA) and dietary calcium (Ca) in BMD, independent of other risk factors. At low and/or medium Ca intakes BMD was higher amongst the most active people. INTRODUCTION: Although there is general agreement that increased activity (PA) and dietary calcium (Ca) consumption may help maintain bone mass in later life and prevent fractures, the amount required remains uncertain. METHODS: In 2001-2003, 1,847 postmenopausal women (mean +/- SD age: 69.3 +/- 5.5 years) underwent bone mineral density (BMD) measurement and, in 2004, 68.7% (n = 1,254) completed a bone-specific Physical Activity Questionnaire (bsPAQ) and a food frequency questionnaire. The bsPAQ measures the metabolic and mechanical components of PA. Interactions of PA and Ca in BMD were examined using ANCOVA. RESULTS: Significant interactions were identified in the BMD of the lumbar spine (LS), right hip (RH) and left hip (LH), after adjustment for confounders, between tertiles of PA classified according to the mechanical component and tertiles of energy-adjusted Ca intake (ANCOVA p = 0.006, p = 0.004 and p = 0.013 respectively). For example, at medium Ca intakes LH BMD was higher by 7.8% in the highest tertile of PA compared with the lowest tertile of PA. CONCLUSIONS: These data suggest that health promotion campaigns to increase PA would be most effective in populations with a low/medium calcium intake.

Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK.

In 1999 and 2000 the Royal College of Physicians published guidelines for the prevention and treatment of osteoporosis [Royal College of Physicians. Osteoporosis: clinical guidelines for the prevention and treatment. London: Royal College of Physicians; 1999; Royal College of Physicians and Bone and Tooth Society of Great Britain. Update on pharmacological interventions and an algorithm for management. London, UK: Royal College of Physicians; 2000.; Royal College of Physicians. Glucocorticoid-induced osteoporosis. Guidelines on prevention and treatment; Bone and Tooth Society of Great Britain, National Osteoporosis Society and Royal College of Physicians. London, UK: Royal College of Physicians; 2002]. Since then, there have been significant advances in the field of osteoporosis including the development of new techniques for measuring bone mineral density, improved methods of assessing fracture risk and new treatments that have been shown to significantly reduce the risk of fractures. Against this background, the National Osteoporosis Guideline Group (NOGG), in collaboration with many Societies in the UK, have updated the original guidelines [Royal College of Physicians, National Osteoporosis Guideline Group on behalf of the Bone Research Society, British Geriatrics Society, British Orthopaedic Association, British Society of Rheumatology, National Osteoporosis Society, Osteoporosis 2000, Osteoporosis Dorset, Primary Care Rheumatology Society, Society for Endocrinology. Osteoporosis. Clinical guideline for prevention and treatment, Executive Summary. University of Sheffield Press; 2008], a practical summary of which is detailed below. The management algorithms are underpinned by a health economic analysis applied to the epidemiology of fracture in the UK.

Hormone replacement therapy (HRT) or etidronate for osteoporosis in postmenopausal asthmatics on glucocorticoids: a randomised factorial trial.

INTRODUCTION: The study was designed to establish the effects of HRT on osteoporosis and fractures over five years in postmenopausal women with asthma receiving regular glucocorticoids and to compare with etidronate. METHODS: Postmenopausal patients receiving inhaled and/or oral glucocorticoids were randomly assigned to HRT, cyclical etidronate, HRT plus cyclical etidronate or no treatment for five years. The trial was multi-centre and aimed to recruit 750 patients. Outcomes were fractures and changes in bone mineral density (BMD). RESULTS: For reasons detailed in the discussion section of the text, only 50 patients were entered. Three did not fulfil the eligibility criteria and were excluded from the analysis. Among the remaining 47 patients, three (6%) experienced new, symptomatic fractures, one on etidronate and two in the no treatment group. New or worsening morphometric fractures of the thoracolumbar spine occurred in 50% of the 22 patients with spinal radiographs on entry and at five years (one HRT, three etidronate, two HRT plus etidronate and five on no treatment). BMD improved by approximately 1% per annum in those receiving HRT and/or etidronate; comparisons of HRT vs no HRT tended to favour HRT but were only statistically significant at proximal femur. The same trends emerged in the etidronate vs no etidronate comparison, but none reached the 5% level of statistical significance. DISCUSSION: For postmenopausal patients receiving glucocorticoids for asthma, HRT appears as effective as etidronate in preventing loss of BMD over five years and may have a similar effect on fracture prevention.

A comparison of the effect of alendronate and risedronate on bone mineral density in postmenopausal women with osteoporosis: 24-month results from FACTS-International.

OBJECTIVES: To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. METHODS: This was a 12-month extension to the Fosamax Actonel Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12-month base study continued taking the same double-blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. RESULTS: Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. CONCLUSIONS: Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability.

Binding of quinine- and quinidine-dependent drug antibodies to platelets is mediated by the Fab domain of the immunoglobulin G and is not Fc dependent.

The antibody domain controlling reactions between platelet membranes and drug-dependent (dd) antibodies from patients with thrombocytopenia induced by cinchona alkaloids was studied using F(ab')2, Fab, and Fc fragments made from purified dd-IgG. By direct binding radioimmunoassay (RIA) measurements, 20,000 to 50,000 antibody molecules bound per platelet equivalent of purified platelet membranes at apparent saturation with three different antibodies. F(ab')2 and Fab fragments bound to platelet membranes drug dependently but Fc fragments did not. The ability of dd-IgG fragments to compete with intact IgG was quantitatively measured by RIA and by complement fixation. F(ab')2 and Fab competed with intact IgG at an 8:1 and greater than 50:1 molar ratio, respectively, in RIA, and at a 1.6-3:1 and 44-75:1 ratio, respectively, by complement fixation assays. Fc did not compete with IgG in either assay. We conclude that the Fab domain supports attachment of dd antibody to the platelet surface.