Study Details Effects of Bisphosphonate Discontinuation After Long-Term Use

New research from Kaiser Permanente Northern California is offering insight into the real-world effects of long-term bisphosphonate use in aging women.

Results of the analysis, which included data from nearly 30,000 women, is offering an overview of the fracture risk associated with discontinuation of bisphosphonate treatment at different time points after initiating the therapy for the prevention of fractures.

With clinical trial data demonstrating the efficacy of bisphosphonate drugs during the first 3-5 years of therapy, questions, and even controversy, exists around long-term use and the effects of discontinuation. With this in mind, a team from Kaiser Permanente Northern California designed the current study to retrospectively assess data from a cohort of more than 29,000 women treated with oral bisphosphonate therapy between January 1, 1997 and September 30, 2009.

Patients were considered eligible for the study if they were treated during the aforementioned period, were aged 45-80 years of age at treatment initiation, received treatment with alendronate, risedronate, or ibandronate, and were at least 60% adherent in each of the 5 years after initiation. Patients included in the study were treated at Kaiser Permanente Northern California and Southern California.

Learn more about controversies in bisphosphonate treatment in a video interview with Dr. Jeffrey Curtis.

The primary outcome of the study was hip fracture. Investigators classified hip fractures using principal hospital discharge diagnoses. For the purpose of analysis, discontinuation of bisphosphonate at study entry, discontinuation at 2 years, and continuation for an additional 5 years were used as exposures. Of note, there was a 6-month grace period included when considering whether or not a patient discontinued at study entry or at 2 years.

In total, 29,865 women were identified for inclusion in the study. This group had a median age of 71 (64-77) years,60% were non-Hispanic white individuals, and 507 reported experiencing an incident hip fracture event. In a comparison with those who discontinued use at study entry, investigators found no differences in cumulative incidence of hip fracture among women who remained on therapy for an additional 2 years (5-year risk difference [RD], -2.2 per 1000 individuals; 95% CI, -20.3 to 15.9) or women who remained on therapy for an additional 5 years (5-year RD, 3.8 per 1000 individuals; 95% CI, -7.4 to 15.0).

Investigators noted 5-year differences in hip fracture risk among those discontinuing after 5 additional years and those discontinuing after 2 additional years were not statistically significant (5-year RD, 6.0 per 1000 individuals; 95% CI, -9.9 to 22.0). However, results of the analysis suggested interim hip fracture appeared to be lower if women discontinued after 2 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 investigators pointed out this was not without a 6-month grace period to define discontinuation.

Investigators cautioned clinicians to consider the limitations of their study before overinterpretation of results. These limitations included the observational nature of the study, the inability to apply these findings to older women at higher risk of osteoporotic fracture, using 60% as an adherence threshold, and the inability to exclude the possibility that the outcome included atypical femur fracture, among others.

This study, “Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women,” was published in JAMA Network Open.