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Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study.

ABSTRACT: BACKGROUND:Orally administered bisphosphonate drugs (i.e., alendronate, etidronate, risedronate) can reduce the risk of vertebral fracture. However, only alendronate and risedronate have proven efficacy in reducing the risk of hip fracture. We sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults. METHODS:We identified new users of orally administered bisphosphonate drugs in British Columbia and Ontario between 2001 and 2008. We used province- and sex-specific propensity score-matching strategies to maximize comparability between exposure groups. We used Cox proportional hazards models to compare time-to-hip fracture within 1 year of treatment between exposures by sex in each province. Our secondary analyses considered hip fracture rates within 2 and 3 years' follow-up. We used alendronate as the reference for all comparisons and pooled provincial estimates using random effects variance-weighted meta-analysis. RESULTS:We identified 321 755 patients who were eligible for inclusion in the study. We found little difference in fracture rates between men (pooled hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74-1.14) or women (pooled HR 1.15, 95% CI 0.73-1.56) taking risedronate and those taking alendronate. We similarly identified little difference in fracture rates between women taking etidronate and those taking alendronate (pooled HR 1.00, 95% CI 0.82-1.18). However, we identified lower rates of hip fracture among men taking etidronate relative to alendronate (pooled HR 0.77, 95% CI 0.60-0.94). Results extended to 2 and 3 years' follow-up were similar. However, with 3 years' follow-up, rates of hip fracture were lower among women in British Columbia who had taken alendronate. INTERPRETATION:We identified little overall difference between alendronate and risedronate in reducing the risk of hip fracture in men or women. Our finding that etidronate is associated with lower fracture risk among men is likely due to selection bias. The long-term comparative effects of orally administered bisphosphonate drugs warrant further study.

SUBMITTER: Cadarette SM

PROVIDER: S-EPMC3986012 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study.

Cadarette Suzanne M SM Lévesque Linda L Mamdani Muhammad M Perreault Sylvie S Juurlink David N DN Paterson J Michael JM Carney Greg G Gunraj Nadia N Hawker Gillian A GA Tadrous Mina M Wong Lindsay L Dormuth Colin R CR

CMAJ open 20130913 3

<h4>Background</h4>Orally administered bisphosphonate drugs (i.e., alendronate, etidronate, risedronate) can reduce the risk of vertebral fracture. However, only alendronate and risedronate have proven efficacy in reducing the risk of hip fracture. We sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults.<h4>Methods</h4>We identified new users of orally administered bisphosphonate drugs in British Columbia and Ont ...[more]

PMID: 25077113

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Project description:ImportanceClinical trials have demonstrated the antifracture efficacy of bisphosphonate drugs for the first 3 to 5 years of therapy. However, the efficacy of continuing bisphosphonate for as long as 10 years is uncertain.ObjectiveTo examine the association of discontinuing bisphosphonate at study entry, discontinuing at 2 years, and continuing for 5 additional years with the risk of hip fracture among women who had completed 5 years of bisphosphonate treatment at study entry.Design, setting, and participantsThis cohort study included women who were members of Kaiser Permanente Northern and Southern California, 2 integrated health care delivery systems, and who had initiated oral bisphosphonate and completed 5 years of treatment by January 1, 2002, to September 30, 2014. Data analysis was conducted from January 2018 to August 2020.ExposureDiscontinuation of bisphosphonate at study entry (within a 6-month grace period), discontinuation at 2 years (within a 6-month grace period), and continuation for 5 additional years.Main outcomes and measuresThe outcome was hip fracture determined by principal hospital discharge diagnoses. Demographic, clinical, and pharmacological data were ascertained from electronic health records.ResultsAmong 29 685 women (median [interquartile range] age, 71 [64-77] years; 17 778 [60%] non-Hispanic White individuals), 507 incident hip fractures were identified. Compared with bisphosphonate discontinuation at study entry, there were no differences in the cumulative incidence (ie, risk) of hip fracture if women remained on therapy for 2 additional years (5-year risk difference [RD], -2.2 per 1000 individuals; 95% CI, -20.3 to 15.9 per 1000 individuals) or if women continued therapy for 5 additional years (5-year RD, 3.8 per 1000 individuals; 95% CI, -7.4 to 15.0 per 1000 individuals). While 5-year differences in hip fracture risk comparing continuation for 5 additional years with discontinuation at 2 additional years were not statistically significant (5-year RD, 6.0 per 1000 individuals; 95% CI, -9.9 to 22.0 per 1000 individuals), interim hip fracture risk appeared lower if women discontinued after 2 additional years (3-year RD, 2.8 per 1000 individuals; 95% CI, 1.3 to 4.3 per 1000 individuals; 4-year RD, 9.3 per 1000 individuals; 95% CI, 6.3 to 12.3 per 1000 individuals) but not without a 6-month grace period to define discontinuation.Conclusions and relevanceIn this study of women treated with bisphosphonate for 5 years, hip fracture risk did not differ if they discontinued treatment compared with continuing treatment for 5 additional years. If women continued for 2 additional years and then discontinued, their risk appeared lower than continuing for 5 additional years. Discontinuation at other times and fracture rates during intervening years should be further studied.

Project description:ObjectivesDefining common patterns of recovery after an acute health stressor (resiliency groups) has both clinical and research implications. We sought to identify groups of patients with similar recovery patterns across 10 outcomes following hip fracture (stressor) and to determine the most important predictors of resiliency group membership.DesignSecondary analysis of three prospective cohort studies.SettingParticipants were recruited from various hospitals in the Baltimore Hip Studies network and followed for up to 1 year in their residence (home or facility).ParticipantsCommunity-dwelling adults aged 65 years or older with recent surgical repair of a hip fracture (n = 541).MeasurementsSelf-reported physical function and activity measures using validated scales were collected at baseline (within 15-22 d of fracture), 2, 6, and 12 months. Physical performance tests were administered at all follow-up visits. Stressor characteristics, comorbidities, and psychosocial and environmental factors were collected at baseline via participant report and chart abstraction. Latent class profile analysis was used to identify resiliency groups based on recovery trajectories across 10 outcome measures and logistic regression models to identify factors associated with those groups.ResultsLatent profile analysis identified three resiliency groups that had similar patterns across the 10 outcome measures and were defined as "high resilience" (n = 163 [30.1%]), "medium resilience" (n = 242 [44.7%]), and "low resilience" (n = 136 [25.2%]). Recovery trajectories for the outcome measures are presented for each resiliency group. Comparing highest with the medium- and low-resilience groups, self-reported pre-fracture function was by far the strongest predictor of high-resilience group membership with area under the curve (AUC) of .84. Demographic factors, comorbidities, stressor characteristics, environmental factors, and psychosocial characteristics were less predictive, but several factors remained significant in a multivariable model (AUC = .88).ConclusionThese three resiliency groups following hip fracture may be useful for understanding mediators of physical resilience. They may provide a more detailed description of recovery patterns in multiple outcomes for use in clinical decision making. J Am Geriatr Soc 67:2519-2527, 2019.

Project description:OBJECTIVES:Bisphosphonates are effective at preventing hip fractures among older adults, yet many patients still fracture while on treatment and may benefit from additional preventive interventions. Little data are specifically available to target such efforts among bisphosphonate users. We aimed to identify predictors of hip fracture unique to frail older adults initiating pharmacologic treatment for osteoporosis. DESIGN:Retrospective cohort using 2008-2013 linked national Minimum Data Set assessments, Medicare claims, and nursing home (NH) facility data. SETTING:NHs in the United States. PARTICIPANTS:Long-stay NH residents 65?years or older who initiated treatment with a bisphosphonate (N = 17 753). Estimates for bisphosphonate initiators were contrasted with those for calcitonin initiators (control group; N = 5348). MEASUREMENTS:Hospitalized hip fracture outcomes were measured using Part A claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for 36 a priori selected potential predictors. RESULTS:The mean (SD) age of the study population was 84 (8) years, 85% were women, and 51% had moderate to severe cognitive impairment. Predictors associated with a higher risk of hip fracture despite bisphosphonate use included age?75?years or older to 85?years (vs ?65 to <75 y; HR = 1.25; 95% CI = 1.02-1.55), female sex (HR = 1.33; 95% CI = 1.06-1.67), white race (vs black race (HR = 1.87; 95% CI = 1.36-2.58), and body mass index = 18.5-24.9 (vs ?30; HR = 1.93; 95% CI = 1.53-2.42). Independent ability to transfer (vs total dependence; HR = 3.11; 95% CI = 1.83-5.30) and occasional urinary incontinence (vs frequent; HR = 1.45; 95% CI = 1.18-1.78) were also important predictors. Dementia, diabetes, psychoactive drug use, and other characteristics were not associated with post-prescribing hip fracture. Predictors did not differ between bisphosphonate and calcitonin users. CONCLUSION:Predictors of hip fracture among frail older adults did not differ between those who were new users of bisphosphonates vs calcitonin. Given the absence of risk factors unique to bisphosphonate users, targeting of fracture prevention efforts should extend beyond pharmacologic therapy to include existing nonpharmacologic therapies, particularly fall prevention strategies. J Am Geriatr Soc 68:256-260, 2020.

Dataset Information

Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study.

Publications

Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study.

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