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

Abstract

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.

Figure 1.. Hip Fracture Survival

Regimen 1 indicates discontinuation of bisphosphonate at study entry; regimen 2, discontinuation after 2 additional years of treatment; regimen 3, continuation of bisphosphonate treatment for all 5 years of follow-up.

Figure 2.. Adjusted Risk Differences for Hip Fracture

Regimen 1 indicates discontinuation of bisphosphonate at study entry; regimen 2, discontinuation after 2 additional years of treatment; regimen 3, continuation of bisphosphonate treatment for all 5 years of follow-up.