Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women | Geriatrics | JAMA Network Open | JAMA Network
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    Original Investigation
    Pharmacy and Clinical Pharmacology
    December 7, 2020

    Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women

    Author Affiliations
    • 1Division of Research, Kaiser Permanente Northern California, Oakland
    • 2Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena
    • 3Department of Medicine, University of Washington School of Medicine, Seattle
    • 4Pharmacy Outcomes Research Group, Kaiser Permanente California, Oakland
    JAMA Netw Open. 2020;3(12):e2025190. doi:10.1001/jamanetworkopen.2020.25190
    Key Points

    Question  Is bisphosphonate therapy beyond 5 years associated with lower risk of hip fracture?

    Findings  In this cohort study of 29 685 older women who completed 5 years of bisphosphonate treatment, if women continued treatment for 5 additional years, the risk of hip fracture was not significantly different than if they discontinued after the first 5 years. If women continued for 2 additional years and then discontinued, there was a difference in hip fracture outcome depending on the use of a grace period for discontinuation.

    Meaning  In this study of women who completed 5 years of bisphosphonate treatment, completing an additional 5 years of treatment was not associated with a reduction in hip fracture risk; the potential hip fracture benefit for continuing 2 additional years but not for 5 additional years should be further studied.


    Importance  Clinical 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.

    Objective  To 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 Participants  This 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.

    Exposure  Discontinuation 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 Measures  The outcome was hip fracture determined by principal hospital discharge diagnoses. Demographic, clinical, and pharmacological data were ascertained from electronic health records.

    Results  Among 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 Relevance  In 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.