Ten-year follow-up of fracture risk in a systematic population-based screening program: the risk-stratified osteoporosis strategy evaluation (ROSE) randomised trial.

Background: Osteoporotic fractures pose a growing public health concern. Osteoporosis is underdiagnosed and undertreated, highlighting the necessity of systematic screening programs. We aimed to evaluate the effectiveness of a two-step population-based osteoporotic screening program. Methods: This ten-year follow-up of the Risk-stratified Osteoporosis Strategy Evaluation (ROSE) randomized trial tested the effectiveness of a screening program utilizing the Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOF) to select women for dual-energy x-ray absorptiometry (DXA) scan following standard osteoporosis treatment. Women residing in the Region of Southern Denmark, aged 65-80, were randomised (single masked) into a screening or a control group by a computer program prior to inclusion and subsequently approached with a mailed questionnaire. Based on the questionnaire data, women in the screening group with a FRAX value ≥15% were invited for DXA scanning. The primary outcome was MOF derived from nationwide registers. ClinicalTrials.gov: NCT01388244, status: Completed. Findings: All randomised women were included February 4, 2010-January 8, 2011, the same day as approached to participate. During follow-up, 7355 MOFs were observed. No differences in incidences of MOF were identified, comparing the 17,072 women in the screening group with the 17,157 controls in the intention-to-treat analysis (IRR 1.01, 0.95; 1.06). However, per-protocol, women DXA-scanned exhibited a 14% lower incidence of MOF (IRR 0.86, 0.78; 0.94) than controls with a FRAX value ≥15%. Similar trends were observed for hip fractures, all fractures, and mortality. Interpretation: While the ROSE program had no overall effect on osteoporotic fracture incidence or mortality it showed a preventive effect for women at moderate to high risk who underwent DXA scans. Hence the overall effect might have been diluted by those who were not at an intervention level threshold risk or those who did not show up for DXA. Using self-administered questionnaires as screening tools may be inefficient for systematic screening due to the low and differential screening uptake. Funding: INTERREG and the Region of Southern Denmark.

Call to action: a five nations consensus on the use of intravenous zoledronate after hip fracture.

Currently in the UK and Ireland, after a hip fracture most patients do not receive bone protection medication to reduce the risk of refracture. Yet randomised controlled trial data specifically examining patients with hip fracture have shown that intravenous zoledronate reduces refracture risk by a third. Despite this evidence, use of intravenous zoledronate is highly variable following a hip fracture; many hospitals are providing this treatment, whilst most are currently not. A range of clinical uncertainties, doubts over the evidence base and practical concerns are cited as reasons. This paper discusses these concerns and provides guidance from expert consensus, aiming to assist orthogeriatricians, pharmacists and health services managers establish local protocols to deliver this highly clinically and cost-effective treatment to patients before they leave hospital, in order to reduce costly re-fractures in this frail population.

Development, implementation and evaluation of a multinational FLS mentorship programme in Latin America.

Realising the benefits of systematic secondary fracture prevention requires supporting local sites to get started and becoming effective. We here describe the development, implementation and impact of a regional fracture liaison service (FLS) mentorship programme in Latin America that led to 64 FLS getting started and coverage of 17,205 patients. INTRODUCTION: Despite treatments and service models to deliver effective secondary fracture prevention, most patients are left untreated after a fragility fracture. To improve the capability to get FLS started and more effective, we describe the development, implementation and evaluation of an international programme to develop national communities of FLS mentors as part of the Capture the Fracture Partnership in Latin America. METHODS: The IOF regional team and the University of Oxford developed the curriculum and associated resources for training mentors in setting up FLS, service improvement and mentorship. Mentors were selected during a preparatory meeting, trained using live online sessions followed by regular mentor-led post-training meetings. The programme was evaluated using a pre-training needs assessment and post-training evaluation based on Moore's outcomes. RESULTS: The mentorship programme was initiated in Mexico, Brazil, Colombia and Argentina. The mentors were multidisciplinary, including orthopaedic surgery, rehabilitation, rheumatology, endocrinology, geriatrics, gynaecology and internal medicine. There was 100% participation in training sessions and reported satisfaction with the training. Since the initiation of the training programme, 22 FLS have been set up in Mexico, 30 in Brazil, 3 in Colombia and 9 in Argentina, in comparison with two in Chile and none in any other LATAM countries that were not involved in the mentorship programme. This equates to approximately 17,025 additional patients identified from 2019 to 2021 after initiation of mentorship. The mentors have engaged with 58 FLS for service development. Post-training activities include two published national best practice guidelines and other country-specific resources for FLS in the local language. CONCLUSION: Despite the COVID pandemic, the mentorship pillar of the Capture the Fracture Partnership has developed a community of FLS mentors with measurable improvement in national FLS provision. The programme is a potentially scalable platform to develop communities of mentors in other countries.

Current approaches to secondary prevention after hip fracture in England and Wales - an analysis of trends between 2016 and 2020 using the National Hip Fracture Database (NHFD).

Hip fractures are strong risk factors for further fractures. However, using the National Hip Fracture Database, we observed that in England and Wales, 64% of patients admitted on oral bisphosphonates were discharged on the same and injectable drug use varies from 0-67% and 0.2%-83.6% were deemed "inappropriate" for bone protection. This variability requires further investigation. INTRODUCTION: A key aim for the National Hip Fracture Database (NHFD) is to encourage secondary fracture prevention of the 75,000 patients who break their hip annually in the UK, through bone health assessment and appropriate provision of anti-osteoporosis medication (AOM). We set out to describe trends in anti-osteoporosis medication prescription and examine the types of oral and injectable AOMs being prescribed both before and after a hip fracture. METHODS: We used data freely available from the NHFD  www.nhfd.co.uk  to analyse trends in oral and injectable AOM prescription across a quarter of a million patients presenting between 2016 and 2020, and more detailed information on the individual type of AOM prescribed for 63,705 patients from 171 hospitals in England and Wales who presented in 2020. RESULTS: Most patients (88.3%) are not taking any AOM when they present with a hip fracture. Half of all patients (50.8%) were prescribed AOM treatment by the time of discharge, but the proportion deemed 'inappropriate for AOM' varied hugely (0.2-83.6%) in different hospitals. Nearly two-thirds (64.2%) of those previously taking an oral bisphosphonate were simply discharged on the same type of medication. The total number of patients discharged on oral medication fell by over a quarter in these five years. The number discharged on injectables increased by nearly three-quarters to 14.2% over the same period, but remains hugely variable across the country, with rates ranging from 0-67% across different units. CONCLUSION: A recent hip fracture is a strong risk factor for future fractures. The huge variability in approaches, and in particular the use of injectables, in different trauma units across England and Wales requires further investigation.

Expected Benefits and Budget Impact From a Microsimulation Model Support the Prioritization and Implementation of Fracture Liaison Services.

Osteoporotic-related fractures cause significant patient disability, leading to a growing burden on health care systems. Effective secondary fracture prevention can be delivered by fracture liaison services (FLSs), but these are not available in most countries. A major barrier is insufficient policy prioritization, helped by the lack of economic assessments using national data and providing estimates of patient outcomes alongside health care resource use and cost impacts. The aim of this study was to develop an economic model to estimate the benefits and budget impact of FLSs and support their wider international implementation. Five interconnected stages were undertaken: establishment of a generic patient pathway; model design; identification of model inputs; internal validation and output generation; and scenario analyses. A generic patient pathway including FLS activities was built to underpin the economic model. A state-based microsimulation model was developed to estimate the impact of FLSs compared with current practice for men and women aged 50 years or older with a fragility fracture. The model provides estimates for health outcomes (subsequent fractures avoided and quality-adjusted life years [QALYs]), resource use, and health and social care costs, including those necessary for FLSs to operate, over 5 years. The model was run for an exemplar country the size of the United Kingdom. FLSs were estimated to lead to a reduction of 13,149 subsequent fractures and a gain of 11,709 QALYs. Hospital-bed days would be reduced by 120,989 and surgeries by 6455, while 3556 person-years of institutional social care would be avoided. Expected costs per QALY gained placed FLSs as highly cost-effective at £8258 per QALY gained over the first 5 years. Ten different scenarios were modeled using different configurations of FLSs. Further work to develop country-specific models is underway to delivery crucial national level data to inform the prioritization of FLSs by policy makers. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Pregnancy Vitamin D Supplementation and Childhood Bone Mass at Age 4 Years: Findings From the Maternal Vitamin D Osteoporosis Study (MAVIDOS) Randomized Controlled Trial.

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter-born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long-term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single-center follow-up of a double-blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25-100 nmol/L from three research centers (2008-2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013-2018). Anthropometry and dual-energy X-ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4-year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472-0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466-0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age- and sex-adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal-child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

How to initiate and develop Fracture Liaison Services (FLS). Recommendations from the IOF Capture the Fracture® FLS Mentors in Brazil.

Expected number of fragility fractures in Brazil, raising the healthcare prioritization for interventions that reduce fracture risk. An FLS is dedicated to managing patient with fragility fracture to reduce risk of another fracture. We review FLSs cost-effectiveness and describe key components to effectively set up FLS in Brazil. PURPOSE: To create a guideline to show health professionals, hospital managers, and stakeholders in Brazil the importance of secondary fracture prevention and how to implement a Fracture Liaison Service. METHODS: We review the cost-effectiveness for FLSs in Brazil. We describe the key components needed to set up an effective FLS including methods for identification, investigation, treatment indication, including bone drugs, supplementation, physical activity, fall prevention, and monitoring. The staffing of FLSs, value of regional clinical networks and quality improvement are also described as a guide for healthcare professionals and decision makers in Brazil. RESULTS: An FLS is a service dedicated to identifying, assessing, recommending treatment, and monitoring patient who present with a fragility fracture reducing the risk of another fracture. FLS has been implemented in Brazil since 2012 overcoming a large geography and a complex health system. Even the limitations, restrictions, differences, and characteristics of each region, it is possible for health institutions to initiate an FLS, adapted to own available resources and meet the stages of identification, investigation, treatment, and monitoring. CONCLUSION: The peculiarity of the Brazilian healthcare system means FLS implementation needs to be tailored to local reality. However, even with limitations, any attempt to capture patients who suffer a fracture due to bone fragility is effective and reduces the risk of further fractures.

Management of patients at very high risk of osteoporotic fractures through sequential treatments.

Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an "anabolic first" approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.

Neuropathic-like Pain in Fibrous Dysplasia/McCune-Albright Syndrome.

CONTEXT: Pain is a major symptom in adults with fibrous dysplasia/McCune-Albright syndrome (FD/MAS) and response to current treatments, including bisphosphonates and standard analgesics (nonsteroidal anti-inflammatory drugs and opiates) is unpredictable. No studies have explored whether the type of pain is variable in this patient group. OBJECTIVE: To determine the frequency of neuropathic-like pain in patients with FD/MAS. DESIGN: Retrospective, dual registry study. SETTING: Community. PATIENTS: FD/MAS online registries: the US-based Familial Dysautonomia Foundation (FDF) and the UK-based Rare and Undiagnosed Diseases (RUDY) study. INTERVENTION: Subjects completed questionnaires to evaluate the presence of features of neuropathic-like pain (painDETECT) and the impact on sleep quality (Pittsburgh Sleep Quality Index) and mental health (Hospital Anxiety and Depression Scale). Descriptive statistics were used to characterize the prevalence and associated burden of neuropathic-like pain. MAIN OUTCOME MEASURES: Incidence of neuropathic, nociceptive, and unclear pain. RESULTS: Of 249 participants, one third experienced neuropathic-like pain. This group had statistically significantly (P < 0.001) worse mental well-being and sleep in comparison to those with predominately nociceptive pain. CONCLUSIONS: Neuropathic-like pain is common in patients with FD/MAS and associated with worse quality of life. Evaluation of pain in patients with FD/MAS should include assessment of neuropathic-like pain to guide personalized approaches to treatment and inform future research.

Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database.

The aim of this study was to evaluate the risk of acute myocardial infarction in patients taking osteoporosis medication. Patients were taken from the SIDIAP or CPRD database and were matched using propensity scores. Patients with diabetes and chronic kidney disease taking SERMs were at an increased risk. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment. INTRODUCTION: This study aims to evaluate the comparative safety of anti-osteoporosis drugs based on the observed risk of acute myocardial infarction while on treatment in a primary care setting. METHODS: This is a propensity-matched cohort study and meta-analysis. This study was conducted in two primary care record databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995-2014 and 2006-2014, respectively. The outcome was acute myocardial infarction while on treatment. Users of alendronate (reference group) were compared to those of (1) other oral bisphosphonates (OBP), (2) strontium ranelate (SR), and (3) selective oestrogen receptor modulator (SERM), after matching on baseline characteristics (socio-demographics, fracture risk factors, comorbidities, and concomitant drug use) using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk (sub-distribution hazard ratios (SHR)) according to therapy. Country-specific data were analysed individually and meta-analysed. RESULTS: A 10% increased risk of acute myocardial infarction was found in users of other bisphosphonates as compared to alendronate users within CPRD. The meta-analysis of CPRD and SIDIAP results showed a 9% increased risk in users of other bisphosphonate as compared to alendronate users. Sensitivity analysis showed SERMS users with diabetes and chronic kidney disease were at an elevated risk. CONCLUSIONS: This study provides additional data on the risk of acute myocardial infarction in patients receiving osteoporosis treatment. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.

Bone turnover in pregnancy, measured by urinary CTX, is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial.

BACKGROUND: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. OBJECTIVES: We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. METHODS: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and ß-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. RESULTS: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 µg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 µg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: ß = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283). CONCLUSIONS: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.

Bariatric surgery increases the rate of major fracture: self-controlled case series study in UK Clinical Practice Research Datalink.

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/m2 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).

Higher prevalence of non-skeletal comorbidity related to X-linked hypophosphataemia: a UK parallel cohort study using CPRD.

OBJECTIVES: X-Linked hypophosphataemic rickets (XLH) is a rare multi-systemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls. METHODS: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995-2016), along with a non-XLH cohort matched (1 : 4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to the Index of Multiple Deprivation (IMD). RESULTS: There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine [OR 3.46 (95% CI: 1.44, 8.31)] and neurological [OR 3.01 (95% CI: 1.41, 6.44)] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 (95% CI: 1.47, 5.92). Distribution of IMD among XLH cases indicated greater deprivation than the general population. CONCLUSION: We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients.

Safety of Oral Bisphosphonates in Moderate-to-Severe Chronic Kidney Disease: A Binational Cohort Analysis.

Bisphosphonates are the first-line treatment for preventing fractures in osteoporosis patients. However, their use is contraindicated or to be used with caution in chronic kidney disease (CKD) patients, primarily because of a lack of information about their safety and effectiveness. We aimed to investigate the safety of oral bisphosphonates in patients with moderate to severe CKD, using primary-care electronic records from two cohorts, CPRD GOLD (1997-2016) and SIDIAP (2007-2015) in the UK and Catalonia, respectively. Both databases were linked to hospital records. SIDIAP was also linked to end-stage renal disease registry data. Patients with CKD stages 3b to 5, based on two or more estimated glomerular filtration rate measurements less than 45 mL/min/1.73 m2 , aged 40 years or older were identified. New bisphosphonate users were propensity score-matched with up to five non-users to minimize confounding within this population. Our primary outcome was CKD stage worsening (estimated glomerular filtration rate [eGFR] decline or renal replacement therapy). Secondary outcomes were acute kidney injury, gastrointestinal bleeding/ulcers, and severe hypocalcemia. Hazard ratios (HRs) were estimated using Cox regression and Fine and Gray sub-HRs were calculated for competing risks. We matched 2447 bisphosphonate users with 8931 non-users from CPRD and 1399 users with 6547 non-users from SIDIAP. Bisphosphonate use was associated with greater risk of CKD progression in CPRD (sub-HR [95% CI]: 1.14 [1.04, 1.26]) and SIDIAP (sub-HR: 1.15 [1.04, 1.27]). No risk differences were found for acute kidney injury, gastrointestinal bleeding/ulcers, or hypocalcemia. Hence, we can conclude a modest (15%) increased risk of CKD progression was identified in association with bisphosphonate use. No other safety concerns were identified. Our findings should be considered before prescribing bisphosphonates to patients with moderate to severe CKD. © 2020 American Society for Bone and Mineral Research (ASBMR).

Rare musculoskeletal diseases in adults: a research priority setting partnership with the James Lind Alliance.

BACKGROUND: Osteogenesis imperfecta, fibrous dysplasia/McCune-Albright syndrome and X-linked hypophosphatemia are three rare musculoskeletal diseases characterised by bone deformities, frequent fractures and pain. Little high-quality research exists on appropriate treatment and long-term management of these conditions in adults. This is further worsened by limited research funding in rare diseases and a general mismatch between the existing research priorities and those of the patients. This partnership adopted the James Lind Alliance approach to identify the top 10 research priorities for rare musculoskeletal diseases in adults through joint patient, carer and healthcare professional collaboration. RESULTS: The initial survey for question collection recruited 198 respondents, submitting a total of 988 questions. 77% of the respondents were patients with a rare musculoskeletal disease. Following out-of-scope question exclusion, repeating query grouping and scientific literature check for answers, 39 questions on treatment and long-term management remained. In the second public survey, 220 respondents, of whom 85% were patients with a rare musculoskeletal disease, their carers, relatives or friends, prioritised these uncertainties, which allowed selection of the top 25. In the last stage, patients, carers and healthcare professionals gathered for a priority setting workshop to reach a consensus on the final top 10 research priorities. These focus on the uncertainties surrounding appropriate treatment and holistic long-term disease management, highlighting several aspects indirect to abnormal bone metabolism, such as extra-skeletal symptoms, psychological care of both patients and their families and disease course through ageing. CONCLUSIONS: This James Lind Alliance priority setting partnership is the first to investigate rare bone diseases. The priorities identified here were developed jointly by patients, carers and healthcare professionals. We encourage researchers, funding bodies and other stakeholders to use these priorities in guiding future research for those affected by rare musculoskeletal disorders.

Hospitalization in fibromyalgia: a cohort-level observational study of in-patient procedures, costs and geographical variation in England.

OBJECTIVES: Fibromyalgia is a complex, debilitating, multifactorial condition that can be difficult to manage. Recommended treatments are usually delivered in outpatient settings; evidence suggests that significant inpatient care occurs. We describe the scale and cost of inpatient care with a primary diagnostic code of fibromyalgia within the English National Health Service. METHODS: We conducted a cohort-level observational study of all patients admitted to hospital due to a diagnosis of fibromyalgia, between 1 April 2014 and 31 March 2018 inclusive, in the National Health Service in England. We used data from Hospital Episode Statistics Admitted Patient Care to study: the age and sex of patients admitted, number and costs of admissions, length of stay, procedures undertaken, class and type of admission, and distribution of admissions across clinical commissioning groups. RESULTS: A total of 24 295 inpatient admissions, costing £20 220 576, occurred during the 4-year study period. Most patients were women (89%) with peak age of admission of between 45 and 55 years. Most admissions were elective (92%). A number of invasive therapeutic procedures took place, including a continuous i.v. infusion (35%). There was marked geographical variation in the prevalence and cost of inpatient fibromyalgia care delivered across the country, even after accounting for clinical commissioning group size. CONCLUSIONS: Many patients are admitted for treatment of their fibromyalgia and given invasive procedures for which there is weak evidence, with significant variation in practice and cost across the country. This highlights the need to identify areas of resource use that can be rationalized and diverted to provide more effective, evidence-based treatment.

Prevalence and Mortality of Individuals With X-Linked Hypophosphatemia: A United Kingdom Real-World Data Analysis.

BACKGROUND: X-linked hypophosphatemia (XLH) is a rare multisystemic disease with a prominent musculoskeletal phenotype. We aim here to improve understanding of the prevalence of XLH across the life course and of overall survival among people with XLH. METHODS: This was a population-based cohort study using a large primary care database in the United Kingdom (UK) from 1995 to 2016. XLH cases were matched by age, gender, and practice to up to 4 controls. Trends in prevalence over the study period were estimated (stratified by age) and survival among cases was compared with that of controls. FINDINGS: From 522 potential cases, 122 (23.4%) were scored as at least possible XLH, while 62 (11.9%) were classified as highly likely or likely (conservative definition). In main analyses, prevalence (95% CI) increased from 3.1 (1.5-6.7) per million in 1995-1999 to 14.0 (10.8-18.1) per million in 2012-2016. Corresponding estimates using the conservative definition were 3.0 (1.4-6.5) to 8.1 (5.8-11.4). Nine (7.4%) of the possible cases died during follow-up, at median age of 64 years. Fourteen (2.9%) of the controls died at median age of 72.5 years. Mortality was significantly increased in those with possible XLH compared with controls (hazard ratio [HR] 2.93; 95% CI, 1.24-6.91). Likewise, among those with likely or highly likely XLH (HR 6.65; 1.44-30.72). CONCLUSIONS: We provide conservative estimates of the prevalence of XLH in children and adults within the UK. There was an unexpected increase in mortality in later life, which may have implications for other fibroblast growth factor 23-related disorders.

Quality Improvement Initiatives in Fragility Fracture Care and Prevention.

PURPOSE OF REVIEW: This review sought to describe quality improvement initiatives in fragility fracture care and prevention. RECENT FINDINGS: A major care gap persists throughout the world in the secondary prevention of fragility fractures. Systematic reviews have confirmed that the Fracture Liaison Service (FLS) model of care is associated with significant improvements in rates of bone mineral density testing, initiation of osteoporosis treatment and adherence with treatment for individuals who sustain fragility fractures. Further, these improvements in the processes of care resulted in significant reductions in refracture risk and lower post-fracture mortality. The primary challenge facing health systems now is to ensure that best practice is delivered effectively in the local healthcare setting. Publication of clinical standards for FLS at the organisational and patient level in combination with the establishment of national registries has provided a mechanism for FLS to benchmark and improve their performance. Major efforts are ongoing at the global, regional and national level to improve the acute care, rehabilitation and secondary prevention for individuals who sustain fragility fractures. Active participation in these initiatives has the potential to eliminate current care gaps in the coming decade.