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Introduction: Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI., Methods and Analysis: Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL., Ethics and Dissemination: The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care., Trial Registration Number: ISRCTN15313991., Competing Interests: Competing interests: All authors report funding from the Efficacy and Mechanism Evaluation programme of the NIHR and non-financial support from Eli Lilly to support this work. BLL reports research grants from Mereo Pharmaceuticals outside this work and consultancy funding from Amgen, UCB, and Gedeon Richter. PO reports that she is an employee of the Brittle Bone Society. SR reports research grants from Kyowa Kirin and Astra-Zeneca outside the submitted work and funding to his institution from Pfizer, Abbvie, Kyowa Kirin, Alexion, Amgen, Cellgene, Janssen-Cilag, Novartis, Eli Lilly, Thornton & Ross, and Sanofi Genzyme and UCB outside the submitted work. SR also reports that he is a member of the Scientific Advisory Board of the Brittle Bone Society. KJ reports consultancy funding from Amgen outside the submitted work and reports that he is chair of the Medical Advisory Board of the Brittle Bone Society. JW reports that she is a member of the Medical Advisory Board of the Brittle Bone Society. CK and CW have no other conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Patients with X-linked hypophosphatemia (XLH) experience multiple musculoskeletal manifestations throughout adulthood., Objective: To describe the burden of musculoskeletal features and associated surgeries across the lifespan of adults with XLH., Methods: Three groups of adults were analyzed: subjects of a clinical trial, participants in an online survey, and a subgroup of the online survey participants considered comparable to the clinical trial subjects (according to Brief Pain Inventory worst pain scores of ≥ 4). In each group, the adults were categorized by age: 18-29, 30-39, 40-49, 50-59, and ≥ 60 years. Rates of 5 prespecified musculoskeletal features and associated surgeries were investigated across these age bands for the 3 groups., Results: Data from 336 adults were analyzed. In all 3 groups, 43% to 47% had a history of fracture, with the proportions increasing with age. The overall prevalence of osteoarthritis was > 50% in all 3 groups, with a rate of 23% to 37% in the 18- to 29-year-old group, and increasing with age. Similar patterns were observed for osteophytes and enthesopathy. Hip and knee arthroplasty was reported even in adults in their 30s. Spinal stenosis was present at a low prevalence, increasing with age. The proportion of adults with ≥ 2 musculoskeletal features was 59.1%, 55.0%, and 61.3% in the clinical trial group, survey group, and survey pain subgroup, respectively., Conclusion: This analysis confirmed high rates of multiple musculoskeletal features beginning as early as age 20 years among adults with XLH and gradually accumulating with age., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4-5D (eGFR < 30 ml/min 1.73 m 2 ). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4-5D. Guidance is provided for clinicians caring for CKD stages 4-5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Conflicting results exist about the relationship between bariatric surgery and fracture risk. Also, prediction of who is at increased risk of fracture after bariatric surgery is not currently available. Hence, we used a combination of a self-controlled case series (SCCS) study to establish the association between bariatric surgery and fracture, and develop a prediction model for postoperative fracture risk estimation using a cohort study. Patients from UK Primary care records from the Clinical Practice Research Datalink GOLD linked to Hospital Episode Statistics undergoing bariatric surgery with body mass index (BMI) ≥30 kg/m 2 between 1997 and 2018 were included in the cohort. Those sustaining one or more fractures in the 5 years before or after surgery were included in the SCCS. Fractures were considered in three categories: (i) any except skull and digits (primary outcome); (ii) major (hip, vertebrae, wrist/forearm, and humerus); and (iii) peripheral (forearm and lower leg). Of 5487 participants, 252 (4.6%) experienced 272 fractures (of which 80 were major and 135 peripheral) and were included in the SCCS analyses. Major fracture risk increased after surgery, incidence rate ratios (IRRs) and 95% confidence intervals (CIs): 2.77 (95% CI, 1.34-5.75) and 3.78 (95% CI, 1.42-10.08) at ≤3 years and 3.1 to 5 years postsurgery when compared to 5 years prior to surgery, respectively. Any fracture risk was higher only in the 2.1 to 5 years following surgery (IRR 1.73; 95% CI, 1.08-2.77) when compared to 5 years prior to surgery. No excess risk of peripheral fracture after surgery was identified. A prediction tool for major fracture was developed using 5487 participants included in the cohort study. It was also internally validated (area under the receiver-operating characteristic curve [AUC ROC] 0.70) with use of anxiolytics/sedatives/hypnotics and female as major predictors. Hence, major fractures are nearly threefold more likely after bariatric surgery. A simple prediction tool with five variables identifies high risk patients for major fracture. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Despite substantial advances in delineation of the epidemiology, pathophysiology, risk assessment and treatment of osteoporosis over the last three decades, a substantial proportion of men and women at high risk of fracture remain untreated - the so-called "treatment gap". This review summarises the important patient-, physician- and policyrelated causes of this treatment gap, before discussing in greater detail: (a) the evidence base for the efficacy of bisphosphonates in osteoporosis; (b) recent evidence relating to the adverse effects of this widely used therapeutic class, most notably atypical femoral fracture and osteonecrosis of the jaw; (c) available strategies to improve both secondary and primary prevention pathways for the management of this disorder., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: Bisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects., Objectives: The aims of each work package were as follows. Work package 1: to study the relationship between bisphosphonate use and chronic kidney disease progression. Work package 2: to study the association between using bisphosphonates and fracture risk. Work package 3: to determine the risks of hypocalcaemia, hypophosphataemia, acute kidney injury and upper gastrointestinal events associated with using bisphosphonates. Work package 4: to investigate the association between using bisphosphonates and changes in bone mineral density over time., Design: This was a new-user cohort study design with propensity score matching., Setting and Data Sources: Data were obtained from UK NHS primary care (Clinical Practice Research Datalink GOLD database) and linked hospital inpatient records (Hospital Episode Statistics) for work packages 1-3 and from the Danish Odense University Hospital Databases for work package 4., Participants: Patients registered in the data sources who had at least one measurement of estimated glomerular filtration rate of < 45 ml/minute/1.73 m 2 were eligible. A second estimated glomerular filtration rate value of < 45 ml/minute/1.73 m 2 within 1 year after the first was requested for work packages 1 and 3. Patients with no Hospital Episode Statistics linkage were excluded from work packages 1-3. Patients with < 1 year of run-in data before index estimated glomerular filtration rate and previous users of anti-osteoporosis medications were excluded from work packages 1-4., Interventions/exposure: Bisphosphonate use, identified from primary care prescriptions (for work packages 1-3) or pharmacy dispensations (for work package 4), was the main exposure., Main Outcome Measures: Work package 1: chronic kidney disease progression, defined as stage worsening or starting renal replacement. Work package 2: hip fracture. Work package 3: acute kidney injury, hypocalcaemia and hypophosphataemia identified from Hospital Episode Statistics, and gastrointestinal events identified from Clinical Practice Research Datalink or Hospital Episode Statistics. Work package 4: annualised femoral neck bone mineral density percentage change., Results: Bisphosphonate use was associated with an excess risk of chronic kidney disease progression (subdistribution hazard ratio 1.12, 95% confidence interval 1.02 to 1.24) in work package 1, but did not increase the probability of other safety outcomes in work package 3. The results from work package 2 suggested that bisphosphonate use increased fracture risk (hazard ratio 1.25, 95% confidence interval 1.13 to 1.39) for hip fractures, but sensitivity analyses suggested that this was related to unresolved confounding. Conversely, work package 4 suggested that bisphosphonates improved bone mineral density, with an average 2.65% (95% confidence interval 1.32% to 3.99%) greater gain in femoral neck bone mineral density per year in bisphosphonate users than in matched non-users., Limitations: Confounding by indication was a concern for the clinical effectiveness (i.e. work package 2) data. Bias analyses suggested that these findings were due to inappropriate adjustment for pre-treatment risk. work packages 3 and 4 were based on small numbers of events and participants, respectively., Conclusions: Bisphosphonates were associated with a 12% excess risk of chronic kidney disease progression in participants with stage 3B+ chronic kidney disease. No other safety concerns were identified. Bisphosphonate therapy increased bone mineral density, but the research team failed to demonstrate antifracture effectiveness., Future Work: Randomised controlled trial data are needed to demonstrate antifracture efficacy in patients with stage 3B+ chronic kidney disease. More safety analyses are needed to characterise the renal toxicity of bisphosphonates in stage 3A chronic kidney disease, possibly using observational data., Study Registration: This study is registered as EUPAS10029., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 17. See the NIHR Journals Library website for further project information. The project was also supported by the National Institute for Health Research Biomedical Research Centre, Oxford.

In a global survey of fracture liaison services, most reported that DXA access met needs. However, adherence to basic DXA quality and reporting procedures was confirmed by only around 50% of institutions and many required education for operators/interpreters. Overall, there is significant variability in the access to, and quality of, DXA services worldwide., Introduction: While the use of dual-energy X-ray absorptiometry (DXA) has been widely adopted worldwide for the assessment of bone mineral density, the quality of DXA facilities is unknown. To address this, a global survey of fracture liaison services (FLS) was conducted by the International Society for Clinical Densitometry (ISCD) and the International Osteoporosis Foundation (IOF) to assess the quality of their DXA facilities., Methods: A questionnaire for the accessibility and quality of DXA services was co-created by representatives of the ISCD and the IOF and made available to institutions who participated in the Capture the Fracture Best Practice Framework. From a list of 331 contacted invitees, 124 FLS centres responded; analyses were based on 121 centres with suitable data., Results: Over 70% of institutions reported that, for over 90% of the time, DXA access met service needs, and the scanning/reporting quality was perceived as excellent. However, 25% of DXA facilities reported not being accredited by a professional/governmental organization, and adherence to some basic DXA quality assurance and reporting procedures was confirmed by < 50% of services. Importantly, in excess of 50% of institutions stated that they desired ongoing education in osteoporosis and DXA for operators and interpreters., Conclusion: There is significant variability in the access to and quality of DXA services for established FLS worldwide. Despite two decades of training initiatives in osteoporosis densitometry, many centres are falling short of the standards of the IOF-ISCD Osteoporosis Essentials criteria.

We aimed to characterize incident users of alendronate from Denmark and Spain, and investigate their eligibility for participation in the pivotal Fracture Intervention Trial (FIT). This is an international cross-sectional study, where the data were obtained from the SIDIAP database (Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària) from Catalonia (Spain) and the Danish Health Registries (DHR). This study included patients who were incident users of alendronate, ≥40 years old with no history of Paget's disease. Our measurements were the proportion of incident users of alendronate who were not eligible to participate in FIT. 14,316 and 21,221 subjects initiated alendronate in 2006-2007 (SIDIAP) and 2005-2006 (DHR), respectively. SIDIAP and DHR alendronate user cohorts had 2347 (16.4 %) and 5275 (24.9 %) subjects aged >80 years old, reported 9 (0.1 %) and 91 (0.4 %) diagnoses of myocardial infarction, 423 (3 %) and 368 (1.7 %) of erosive gastro-intestinal disease, 200 (1.4 %) and 1109 (5.2 %) of dyspepsia, and 349 (2.4 %) and 149 (0.7 %) of metabolic bone disease, all of which were exclusion criteria in FIT. Men [3818 (26.7 %) in SIDIAP and 3885 (18.3 %) in DHR] and glucocorticoid users [1229 (8.6 %) in SIDIAP and 4716 (22.2 %) in DHR] were also excluded from the FIT trial. Overall, 3447 (35.4 %) SIDIAP and 6228 (44.5 %) (when not considering men and glucocorticoid users) DHR of incident alendronate users would have been excluded from FIT. One in two real-life users of alendronate exhibited one or more clinical characteristics that would have led to them being excluded from the FIT trial.

Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. "Cluster 1" contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. "Cluster 2" contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p<0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone., (Copyright © 2016. Published by Elsevier Inc.)

The objective of this work was to study the associations between ankylosing spondylitis (AS) and clinical vertebral and nonvertebral fractures. Data from a large population-based public health database in Spain, Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP), were used in this parallel cohort study. All participants registered in SIDIAP on January 1, 2006, were screened to identify those with a diagnosis of AS. Five age-matched, gender-matched, and general practice surgery-matched controls were selected for each patient with AS. All participants were followed until December 31, 2011, transfer out date, or death date. Fractures during this time were classified as vertebral or nonvertebral. Adjustment was made for potential confounders (tobacco smoking, alcohol consumption, body mass index, and use of oral steroids). Of 4,920,353 eligible patients in SIDIAP, 6474 AS patients with matched controls (n = 32,346) were available. A higher proportion of patients with AS versus controls had clinical vertebral (0.86% versus 0.41%) and nonvertebral (3.4% versus 2.7%) fractures. Adjusted Cox regression models showed an increased risk of clinical vertebral (hazard ratio [HR] 1.93; 95% confidence interval [CI], 1.39 to 2.68; p < 0.001) and nonvertebral (HR 1.19; 95% CI, 1.02 to 1.39; p = 0.03) fractures among patients with AS. However, the observed increased risks were apparent only in those not on regular nonsteroidal anti-inflammatory drugs (NSAIDs). There were no interactions with inflammatory bowel disease, psoriasis, or previous back pain. Patients with AS are at increased risk of vertebral and nonvertebral clinical fractures, independently of various risk factors. Regular use of NSAIDs appears to eliminate the excess fracture risk related to AS, but the mechanisms involved are unknown., (© 2014 American Society for Bone and Mineral Research.)

Fractures in obese older individuals contribute significantly to the overall burden on primary health care, but data on their impact on mortality are lacking. We studied the association between obesity and mortality following hip and nonhip clinical fractures in a retrospective, population-based cohort study. The Sistema d'Informació pel Desenvolupament de la Investigació en Atenció Primària (SIDIAP(Q) ) database contains primary care computerized medical records of a representative sample of >2.1 million people (35% of the population) in Catalonia (Spain), linked to hospital admissions data. We included in this analysis anyone aged 40 years and older suffering a hip or nonhip clinical fracture in 2007 to 2009 in the SIDIAP(Q) database. The main exposure was the most recent body mass index (BMI) measured before fracture, categorized as underweight (<18.5 kg/m2), normal (18.5 to <25 kg/m2 ), overweight (25 to <30 kg/m2), and obese (≥30 kg/m2). Furthermore, the study outcome was all-cause mortality in 2007 to 2009 as provided to SIDIAP(Q) by the National Office of Statistics. Time to death after fracture was modeled using Cox regression. Multivariate models were adjusted for age, gender, smoking, alcohol intake, oral glucocorticoid use, and Charlson comorbidity index. Within the study period, 6988 and 29,372 subjects with a hip or nonhip clinical fracture were identified and followed for a median (interquartile range) of 1.17 (0.53-2.02) and 1.36 (0.65-2.15) years, respectively. Compared to subjects of normal weight, adjusted hazard ratios (HRs) for mortality in overweight and obese subjects were 0.74 (95% CI, 0.62-0.88; p = 0.001) and 0.74 (95% CI, 0.60-0.91; p = 0.004) after hip and 0.50 (95% CI, 0.32-0.77; p = 0.002), 0.56 (95% CI, 0.36-0.87; p = 0.010) after nonhip fracture. In conclusion, the highest mortality was observed in individuals with low BMI, but compared to subjects of normal weight, obese and overweight individuals survived longer following fracture. The latter observation is consistent with data reported in other chronic conditions, but the reasons for reduced mortality in obese and overweight subjects when compared to those of normal weight require further research., (© 2014 American Society for Bone and Mineral Research.)

Although oral bisphosphonates (BPs) are highly effective in preventing fractures, some patients will fracture while on treatment. We identified predictors of such fractures in a population-based cohort of incident users of oral BPs. We screened the Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) database to identify new users of oral BPs in 2006-2007. SIDIAP includes pharmacy invoice data and primary care electronic medical records for a representative 5 million people in Catalonia (Spain). Exclusion criteria were the following: Paget disease; <40 years of age; and any antiosteoporosis treatment in the previous year. A priori defined risk factors included age, gender, body mass index, vitamin D deficiency, smoking, alcohol drinking, preexisting comorbidities, and medications. Fractures were considered if they appeared at least 6 months after treatment initiation. "Fractures while on treatment" were defined as those occurring among participants persisting for at least 6 months and with an overall high compliance (medication possession ratio ≥80%). Fine and Gray survival models accounting for competing risk with therapy discontinuation were fitted to identify key predictors. Only 7449 of 21,385 (34.8%) participants completed >6 months of therapy. Incidence of fracture while on treatment was 3.4/100 person-years (95% confidence interval [CI], 3.1-3.7). Predictors of these among patients persisting and adhering to treatment included: older age (subhazard ratio [SHR] for 60 to <80 years, 2.18 [95% CI, 1.70-2.80]; for ≥80 years, 2.5 [95% CI, 1.82-3.43]); previous fracture (1.75 [95% CI, 1.39-2.20] and 2.49 [95% CI, 1.98-3.13], in the last 6 months and longer, respectively); underweight, 2.11 (95% CI, 1.14-3.92); inflammatory arthritis, 1.46 (95% CI, 1.02-2.10); use of proton pump inhibitors (PPIs), 1.22 (95% CI, 1.02-1.46); and vitamin D deficiency, 2.69 (95% CI, 1.27-5.72). Even among high compliers, 3.4% of oral BP users will fracture every year. Older age, underweight, vitamin D deficiency, PPI use, previous fracture, and inflammatory arthritides increase risk. Monitoring strategies and/or alternative therapies should be considered for these patients., (© 2014 American Society for Bone and Mineral Research.)

Objectives: Patients with osteoarthritis have increased bone mass but no decrease in fractures. The association between self-reported osteoarthritis and incident falls and fractures was studied in postmenopausal women., Methods: The Global Longitudinal Study of Osteoporosis in Women is a prospective multinational cohort of 60,393 non-institutionalised women aged ≥55 years who had visited primary care practices within the previous 2 years. Questionnaires were mailed at yearly intervals. Patients were classified as having osteoarthritis if they answered yes to the question, 'Has a doctor or other health provider ever said that you had osteoarthritis or degenerative joint disease?', and this was validated against primary care records in a subsample. Information on incident falls, fractures and covariates was self-reported. Cox and Poisson models were used for incident fractures and number of falls, respectively, to compute hazard ratios (HRs) and rate ratios (RRs) for baseline osteoarthritis status., Results: Of 51 386 women followed for a median of 2.9 years (interquartile range 2.1-3.0), 20 409 (40%) reported osteoarthritis. The adjusted HR for osteoarthritis predicting fracture was 1.21 (95% CI 1.13 to 1.30; p<0.0001) and the adjusted RR for falls was 1.24 (95% CI 1.22 to 1.26; p<0.0001). However, the association between osteoarthritis and fracture was not significant after adjustment for incident falls (HR 1.06 (95% CI 0.98 to 1.15; p=0.13))., Conclusions: Postmenopausal women with self-reported osteoarthritis have a 20% increased risk of fracture and experience 25% more falls than those without osteoarthritis. These data suggest that increased falls are the causal pathway of the association between osteoarthritis and fractures.

Summary: The aim of this study was to evaluate fracture risk after onset of myasthenia gravis using the UK General Practice Research Database. Overall fracture risk is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use, but was increased in those using antidepressants, anxiolytics or anticonvulsants., Introduction: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. The aim of this study was to evaluate the risk of fracture after onset of MG., Methods: We conducted a retrospective cohort study using the UK General Practice Research Database (1987-2009). Each MG patient was matched by age, sex, calendar time and practice to up to six patients without a history of MG and we identified all fractures and those associated with osteoporosis., Results: Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84-1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67-1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31-3.14]) compared with MG patients without glucocorticoid exposure. However, fracture risk was higher in patients with MG prescribed antidepressants (AHR 3.27 [95 % CI, 1.63-6.55]), anxiolytics (AHR 2.18 [95 % CI, 1.04-4.57]) and anticonvulsants (AHR 6.88 [95 % CI, 2.91-16.27])., Conclusion: Overall risk of fracture in patients with MG is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use but was increased in those using antidepressants, anxiolytics or anticonvulsants. These findings have implications in strategies preserving bone health in patients with MG.

Objective: The association between osteoarthritis (OA) and fractures remains unclear. OA patients have increased bone mass, but no corresponding decrease in fracture rate. This study was undertaken to determine the fracture rates in patients with hip OA undergoing a total hip replacement (THR), as compared with disease-free controls, and to assess the association between bisphosphonate use and postsurgery fracture risk., Methods: We conducted a population-based parallel-cohorts study. All patients in the UK General Practice Research Database undergoing a THR for hip OA between 1986 and 2006 constituted the exposed cohort (n = 14,133). Five disease-free controls were matched with each patient by age, sex, and practice site. Subjects were followed up for 5 years before and after surgery. Fracture rates and rate ratios (RRs) were estimated using Poisson regression. In addition, bisphosphonate use was identified among patients undergoing THR, and the data, stratified by the presence or absence of a previous fracture and by treatment propensity score, were assessed using fitted Cox models to study the effect of bisphosphonate use on the risk of fracture postsurgery., Results: Patients undergoing a THR had a similar fracture risk as that in controls in the 5 years before THR, but had higher rates postsurgery, which peaked at years 2.5-5 (adjusted RR 1.24, 95% confidence interval [95% CI] 1.02-1.52). Use of bisphosphonates lowered the fracture risk among THR patients who received bisphosphonates as primary prevention (hazard ratio [HR] 0.56, 95% CI 0.38-0.82) and also among THR patients who had experienced a previous osteoporotic fracture (HR 0.48, 95% CI 0.23-0.99)., Conclusion: This study identified a 25% increase in fracture risk at 2.5-5 years postsurgery among patients undergoing a THR. Bisphosphonate use reduced the post-THR risk of fracture when administered both as primary prevention and as secondary prevention, by 44% and 52%, respectively. This must be further confirmed in randomized controlled trials., (Copyright © 2011 by the American College of Rheumatology.)

Osteoporosis is a common skeletal condition that results in significant morbidity, mortality and health care costs. There is an increased awareness of bone health in people with severe mental illness (SMI). These people appear to be at a higher risk of low bone density and fracture, and also have a poorer outcome following hip fracture. The reason for the increased risk of osteoporosis is multifactorial and includes general as well as disease-specific factors, such as antipsychotic medication and hyperprolactinaemia. Clinical history and examination followed by dual energy x-ray absorptiometry are required to assess the risk of osteoporosis. Therapies should begin with lifestyle measures, such as physical activity and dietary supplementation, with the use of bone-specific agents reserved for those at high absolute risk.

Background & Aims: Although patients with inflammatory bowel disease (IBD) have reduced bone mass, there is controversy whether there is an increased risk of fracture. This study examines the risk of fracture and its predictors in patients with IBD., Methods: In a primary care- based nested case-control study, 231,778 fracture cases and 231,778 age- and sex-matched controls were recruited. A history of IBD was assessed from medical records., Results: The prevalence of IBD was 156 and 282 per 100,000 for Crohn's disease (CD) and ulcerative colitis (UC), respectively. Patients with IBD had an increased risk of vertebral fracture (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.61) and hip fracture (OR, 1.59; 95% CI, 1.14-2.23). The risk of hip fracture was greater in patients with CD (OR, 1.86; 95% CI, 1.08-3.21) compared with UC (OR, 1.40; 95% CI, 0.92-2.13). Disease severity, assessed by the number of symptoms, predicted fracture even after adjusting for corticosteroid use (OR, 1.46; 95% CI, 1.04-2.04). Only 13% of patients with IBD who had already sustained a fracture were on any form of antifracture treatment., Conclusions: Patients with IBD have a higher risk of fracture due to both disease activity and use of oral corticosteroids. However, few of these patients are receiving optimal bone-sparing therapy, highlighting the importance of increasing awareness of osteoporosis in those managing these patients.

The high rate of osteoporotic fracture in Western populations has resulted in a significant burden in terms of morbidity, mortality and health care costs. The use of DXA has made the diagnosis of osteoporosis easier and identified a subgroup of individuals who are at a higher risk of fracture. It is a useful tool in determining therapy in those at greatest risk of fracture. However, widespread use of such treatments is low and greater uptake remains an elusive goal. There are now many different treatments that reduce fracture rate, and can accompany lifestyle measures such as smoking cessation, diet and exercise. Dietary supplementation with calcium has been shown to reduce the risk of vertebral fracture, and the combination of calcium with vitamin D has been shown to reduce fracture at non-vertebral sites, including the hip. Although ERT, SERMs and tibolone all retard bone loss, prospective fracture prevention has only been shown for SERMs and then only at the spine. Bisphosphonates represent a class of potent anti-resorptive agents, which have been shown to reduce fracture rate at vertebral and non-vertebral sites. Other agents such as calcitonin, PTH and fluoride are of less certain benefit in preventing fracture., (Copyright 2001 Harcourt Publishers Ltd.)