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Izano MA, Lo JC, Adams AL, et al. Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women. JAMA Netw Open. 2020;3(12):e2025190. doi:10.1001/jamanetworkopen.2020.25190
Is bisphosphonate therapy beyond 5 years associated with lower risk of hip fracture?
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.
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.
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.
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.
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.
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.