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We estimated and characterized the imminent fracture risk (1-2 years) of high-risk fracture patients through a multinational (UK, Spain, Denmark) cohort study. Older individuals with newly diagnosed osteoporosis and individuals who had a fracture while on treatment with a bisphosphonate were at a high risk of imminent fracture., Purpose: To characterize and estimate 1- to 2-year fracture risk in high-risk fracture patients., Methods: Multi-cohort study in (database/study period) UK (CPRD/1995-2017), Spain (SIDIAP/2006-2016) and Denmark (DHR/1995-2016) including individuals ≥ 50 years old in NDO (newly diagnosed osteoporosis), OFx (incident osteoporotic fracture), BP (incident oral bisphosphonates use) or FWOT (fracture while on treatment with bisphosphonates). Outcomes (ICD-10/READ): hip, clinical spine, non-hip, non-spine and hip/humerus/distal forearm fracture., Follow-Up: from cohort entry until death, migration/transfer or end of the study., Statistics: baseline characteristics and incidence rate (IR per 1000 persons). RESULTS (1-YEAR IR): NDO included 69,899 (UK), 37,901 (Spain) and 158,191 (Denmark) individuals. Spanish-IR was lowest for hip (4.7), clinical spine (2.5) and major osteoporotic fracture (MOF) (17.3) and highest in Denmark (74.2, 26.0 and 120.1, respectively). OFx included 83,514 (UK), 51,044 (Spain) and 509,551 (Denmark) individuals. IR in Denmark was highest for hip (24.1) and MOF (47.2), in Spain was highest for the clinical spine (9.4) and lowest for hip (9.5) and in the UK was lowest for the clinical spine (2.8) and MOF (20.7). BP included 148,507 (UK), 52,037 (Spain) and 204,010 (Denmark) individuals. Spanish-IR was lowest for hip (5.0) and MOF (21.1) and highest in Denmark (20.3 and 48.6, respectively). FWOT included 28,930 (UK), 1,865 (Spain) and 31,882 (Denmark) individuals. Clinical spine-IR was highest for Spain (12.0). Hip-IR was lowest for Spain (7.6) and highest for Denmark (33.6). Comparing young subjects, those who have FWOT started with an increased fracture rate., Conclusion: OFx and FWOT individuals experience higher re-fracture incidence rates than those with osteoporosis with or without treatment., (© 2021. The Author(s).)

The availability of anti-osteoporosis medications with rapid onset and high potency requires tools to identify patients at high imminent fracture risk (IFR). There are few tools that predict a patient's IFR. We aimed to develop and validate tools for patients with a recent fracture and for patients initiating oral bisphosphonate therapy. Models for two separate cohorts, those with incident fragility fracture (IFx) and with incident oral bisphosphonate prescription (OBP), were developed in primary care records from Spain (SIDIAP database), UK (Clinical Practice Research Datalink GOLD), and Denmark (Danish Health Registries). Separate models were developed for hip, major, and any fracture outcomes. Only variables present in all databases were included in Lasso regression models for the development and logistic regression models for external validation. Discrimination was tested using area under curve (AUC) and calibration was assessed using observed versus predicted risk plots stratified by age, sex, and previous fracture history. The development analyses included 35,526 individuals in the IFx and 41,401 in the OBP cohorts, with 671,094 in IFx and 330,256 in OBP for the validation analyses. Both the IFx and OBP models demonstrated similarly good performance for hip fracture at 1 year (with AUCs of 0.79 [95% CI 0.75 to 0.82] and 0.87 [0.83 to 0.91] in Spain, 0.71 [0.71 to 0.72] and 0.73 [0.72 to 0.74] in the UK, and 0.70 [0.70 to 0.70] and 0.69 [0.68 to 0.70] in Denmark), and lower discrimination for major osteoporotic and any fracture sites. Calibration was good across all three countries. Discrimination and calibration for the 2-year models was similar. The proposed IFR prediction models could be used to identify more precisely patients at high imminent risk of fracture and inform anti-osteoporosis treatment selection. The freely available model parameters permit local validation and implementation. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

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 m 2 , 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)., (© 2020 American Society for Bone and Mineral Research (ASBMR).)

To examine the prevalence of chronic disease and mental health problems in retired professional, male jockeys compared to an age-matched reference population. A cross-sectional study comparing data from a cohort of retired professional jockeys with an age-matched general population sample. Male participants (age range: 50-89 years old) were used to compare health outcomes of self-reported physician-diagnosed conditions: heart disease, stroke, diabetes, hypertension, osteoporosis, osteoarthritis, depression and anxiety between study populations. Conditional logistic regression models were used to estimate associations between study groups and health outcome. In total, 810 participants (135 retired professional male jockeys and 675 participants from the reference population) were included, with an average age of 64.7±9.9 years old. Increased odds of having osteoporosis (OR=6.5, 95%CI 2.1-20.5), osteoarthritis (OR=7.5, 95%CI 4.6-12.2), anxiety (OR=2.8, 95%CI 1.3-5.9) and depression (OR=2.6, 95%CI 1.3-5.7) were seen in the retired professional jockeys. No differences were found for the remaining health outcomes. Retired professional jockeys had increased odds of musculoskeletal disease and mental health problems compared to the general population. Understanding the prevalence of chronic disease and mental health problems in retired professional jockeys will help inform screening and intervention strategies for jockeys., Competing Interests: Authors declare that they have no conflict of interest., (Eigentümer und Copyright ©Georg Thieme Verlag KG 2018.)

In the general population, physical activity is associated with improved health outcomes. However, long-term sports participation may be associated with adverse outcomes, particularly at the elite level. The aims of this study were to assess morbidity and health-related quality of life (HrQoL) amongst former rugby players, compared to an age-standardised general population sample. A cross-sectional study of former elite, male, rugby players (n = 259) was undertaken, and standardised morbidity ratios (SMR) calculated, assessing morbidity prevalence relative to English Longitudinal Study of Aging participants (ELSA, n = 5186). HrQoL, measured using the EQ-5D, was compared to a Health Survey for England (HSE, n = 2981) sample. In SMR analyses of participants aged 50+, diabetes was significantly lower amongst former players, (0.28, 95% CI 0.11-0.66), whereas osteoarthritis (4.00, 95% CI 3.32-4.81), joint replacement (6.02, 95% CI 4.66-7.77), osteoporosis (2.69, 95% CI 1.35-5.38), and anxiety (2.00, 95% CI 1.11-3.61) were significantly higher. More problems in HrQoL were reported amongst former players within the domains of mobility (p < 0.001), self-care (p = 0.041), usual activities (p < 0.001) and pain/discomfort (p < 0.001). Morbidity and HrQoL differ between players and the general population, with higher musculoskeletal morbidity and lower diabetes amongst former players. The magnitude of musculoskeletal morbidity may warrant proactive osteoarthritis management within this population.

In January 2005, the National Institute for Health and Care Excellence (NICE) in England and Wales provided new guidance on the use of antiosteoporosis therapies for the secondary prevention of osteoporotic fractures. This was shortly followed in the same year by market authorization of a generic form of alendronic acid within the UK. We here set out to estimate the actual practice impact of these events among hip fracture patients in terms of antiosteoporosis medication prescribing and subsequent fracture incidence using primary care data (Clinical Practice Research Datalink) from 1999 to 2013. Changes in level and trend of prescribing and subsequent fracture following publication of NICE guidance and availability of generic alendronic acid were estimated using an interrupted time series analysis. Both events were considered in combination within a 1-year "intervention period." We identified 10,873 primary hip fracture patients between April 1999 and Sept 2012. Taking into account prior trend, the intervention period was associated with an immediate absolute increase of 14.9% (95% CI, 10.9 to 18.9) for incident antiosteoporosis prescriptions and a significant and clinically important reduction in subsequent major and subsequent hip fracture: -0.19% (95% CI, -0.28 to -0.09) and -0.17% (95% CI, -0.26 to -0.09) per 6 months, respectively. This equated to an approximate 14% (major) and 22% (hip) reduction at 3 years postintervention relative to expected values based solely on preintervention level and trend. We conclude that among hip fracture patients, publication of NICE guidance and availability of generic alendronic acid was temporally associated with increased prescribing and a significant decline in subsequent fractures. © 2016 American Society for Bone and Mineral Research., Competing Interests: Declaration of interests JL, DPA, NKA, CC, MKJ and AJ received grants from NIHR HS&DR during the conduct of the study. Outside the submitted work, MKJ reports personal fees from Lilly UK, Amgen, Sevier, Merck, Medtronic, Internis, Consilient Health and serves on the Scientific Committee of the National Osteoporosis Society and International Osteoporosis Foundation; DPA received grants from Bioiberica S.A. and Amgen Spain S.A.; CC received personal fees from Servier, Amgen, Eli Lilly, Merck, Medtronic and Novartis. NKA reports personal fees from Merck, Smith and Nephew, Q-Med, Nicox, Flexion, Bioiberica, Servier and grants and personal fees from Roche. AJ has received consultancy, lecture fees and honoraria from Servier, UK Renal Registry, Oxford Craniofacial Unit, IDIAP Jordi Gol, Freshfields Bruckhaus Deringer, has held advisory board positions (which involved receipt of fees) from Anthera Pharmaceuticals, INC., and received research sponsorship from ROCHE. SH and AD have no competing financial interests relevant to the submitted work., (© 2016 American Society for Bone and Mineral Research.)

The objective of this work was to estimate the incidence rate of cardiovascular disease (CVD) events (myocardial infarction, stroke, or CVD death) at 1 year among three cohorts of patients at high risk of fracture (osteoporosis, previous fracture, and anti‐osteoporosis medication) and to identify the key risk factors of CVD events in these three cohorts. To do so, this prospective cohort study used data from the Clinical Practice Research Datalink, a primary care database from United Kingdom. Major adverse cardiovascular events (MACE, a composite outcome for the occurrence of either myocardial infarction [MI], stroke, or CVD death) were identified in patients aged 50 years or older at high or imminent fracture risk identified in three different cohorts (not mutually exclusive): recently diagnosed with osteoporosis (OST, n = 65,295), incident fragility fracture (IFX, n = 67,065), and starting oral bisphosphonates (OBP, n = 145,959). About 1.90%, 4.39%, and 2.38% of the participants in OST, IFX, and OBP cohorts, respectively, experienced MACE events. IFX was the cohort with the higher risk: MACE incidence rates (cases/1000 person‐years) were 19.63 (18.54–20.73) in OST, 52.64 (50.7–54.5) in IFX, and 26.26 (25.41–27.12) in OBP cohorts. Risk of MACE events at 1 year was predicted in the three cohorts. Models using a set of general, CVD, and fracture candidates selected by lasso regression had a good discrimination (≥70%) and internal validity and generally outperformed the models using only the CVD risk factors of general population listed in QRISK tool. Main risk factors common in all MACE models were sex, age, smoking, alcohol, atrial fibrillation, antihypertensive medication, prior MI/stroke, established CVD, glomerular filtration rate, systolic blood pressure, cholesterol levels, and number of concomitant medicines. Identified key risk factors highlight the differences of patients at high risk of fracture versus general population. Proposed models could improve prediction of CVD events in patients with osteoporosis in primary care settings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

ABSTRACT Fracture liaison services are recommended as a model of best practice for organizing patient care and secondary fracture prevention for hip fracture patients, although variation exists in how such services are structured. There is considerable uncertainty as to which model is most cost-effective and should therefore be mandated. This study evaluated the cost- effectiveness of orthogeriatric (OG)- and nurse-led fracture liaison service (FLS) models of post-hip fracture care compared with usual care. Analyses were conducted from a health care and personal social services payer perspective, using a Markov model to estimate the lifetime impact of the models of care. The base-case population consisted of men and women aged 83 years with a hip fracture. The risk and costs of hip and non-hip fractures were derived from large primary and hospital care data sets in the UK. Utilities were informed by a meta-regression of 32 studies. In the base-case analysis, the orthogeriatric-led service was the most effective and cost-effective model of care at a threshold of £30,000 per quality-adjusted life years gained (QALY). For women aged 83 years, the OG-led service was the most cost-effective at £22,709/QALY. If only health care costs are considered, OG-led service was cost-effective at £12,860/QALY and £14,525/QALY for women and men aged 83 years, respectively. Irrespective of how patients were stratified in terms of their age, sex, and Charlson comorbidity score at index hip fracture, our results suggest that introducing an orthogeriatrician-led or a nurse-led FLS is cost-effective when compared with usual care. Although considerable uncertainty remains concerning which of the models of care should be preferred, introducing an orthogeriatrician-led service seems to be the most cost-effective service to pursue. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Limited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality. We sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity. We performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema. We identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment. People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures. [ABSTRACT FROM AUTHOR]