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Background: Little information is available on the comparative effectiveness of osteoporosis pharmacotherapies. Objective: To compare the relative effectiveness of osteoporosis treatments to reduce nonvertebral fracture risk among older adults. Design: Cohort study. Setting: Enrollees in 2 statewide pharmaceutical benefit programs for persons age 65 years or older. Patients: 43 135 new recipients of oral bisphosphonates, nasal calcitonin, and raloxifene who began treatment from 2000 to 2005. The mean age was 79 years (SD, 6.9), and 96% were women. Measurements: The primary outcome was nonvertebral fracture (hip, humerus, or radius or ulna) within 12 months of treatment initiation. Cox proportional hazard models stratified by state and adjusted for risk factors for fracture were used to compare fracture rates. Alendronate was the reference category in all analyses. Results: A total of 1051 nonvertebral fractures were observed within 12 months (2.62 fractures per 100 person-years). No large differences in fracture risk were found between risedronate (hazard ratio [HR], 1.01 [95% CI, 0.85 to 1.21]) or raloxifene (HR, 1.18 [CI, 0.96 to 1.46]) and alendronate. However, among those with a fracture history, raloxifene recipients experienced more nonvertebral fractures within 12 months (HR, 1.78 [CI, 1.20 to 2.63]) compared with alendronate recipients. Patients who received calcitonin experienced more nonvertebral fractures than those who received alendronate (HR, 1.40, [CI, 1.20 to 1.63]). Results were similar in sensitivity analyses that examined different lengths of follow-up (6 months and 24 months), were restricted to hip fracture as the outcome, and were completed in various subgroups. Limitation: Confounder adjustment was limited to health care utilization data, and the confidence bounds of some comparisons were too wide to rule out potential clinically important differences between agents. Conclusion: Differences in fracture risk between risedronate or raloxifene and alendronate were small. Nasal calcitonin recipients may have a higher risk for nonvertebral fractures compared with alendronate recipients. Future studies that can better adjust for possible confounding may further clarify these relationships. [ABSTRACT FROM AUTHOR]

Background: An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter.Objective: To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy.Design: Population-based, matched, cohort study.Setting: Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020.Patients: Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday.Measurements: The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups.Results: A total of 25 077 propensity score-matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]).Limitation: Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events.Conclusion: Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk.Primary Funding Source: Canadian Institutes of Health Research. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the existence of bias during prescription and over-the-counter calcium and vitamin D supplementation in older people with osteoporosis and fracture risk.