Clinical Question

Does long-term use of bisphosphonates increase the risk of fractures in older women?

Bottom Line

In this cohort study, older women at a high risk of fractures who used oral bisphosphonates for 10 to 13 years had a higher risk of fractures than women who used bisphosphonates for only two years. (Level of Evidence = 2b)

Synopsis

The Women's Health Initiative had two components: a randomized trial that busted a bunch of myths about hormone therapy and an observational study with nearly 100,000 women that serves as the basis for this study. These authors pulled a subset of women who had taken an oral bisphosphonate for at least two years, had follow-up data, and who had a FRAX score placing their five-year fracture risk at 1.5% or higher. Additionally, the authors excluded women who took medications that affect bone metabolism (e.g., calcitonin, parathyroid hormone, aromatase inhibitors). Ultimately, they included 5,120 women. They then compared the rate of clinical fractures in women who had taken oral bisphosphonates for only two years with the rate of those who had taken them for three to five years, six to nine years, and 10 to 13 years. It would have been helpful if they had included a group of women with no bisphosphonate exposure.

The women were, on average, 80 years of age. The women had an average of four years of follow-up data and reported 127 hip fractures, 159 wrist or forearm fractures, 235 clinical vertebral fractures, and a total of 1,313 clinical fractures (presumably hip plus wrist plus forearm plus clinical vertebral plus all other fractures). After taking into account other factors that might influence the rate of fractures, 10 to 13 years of bisphosphonate use was associated with a higher risk of any clinical fracture (but not at any single specific site) than two years of use (hazard ratio = 1.29; 95% confidence interval, 1.07 to 1.57). There was no significant association between intermediate-term use of bisphosphonates and fracture risk. When the authors looked only at women with a fracture after 54 years of age, the relationship between long-term bisphosphonate use and subsequent fracture remained.

Study design: Cohort (prospective)

Funding source: Government

Setting: Population-based

Reference: DrielingRLLaCroixAZBeresfordSAAet alLong-term oral bisphosphonate therapy and fractures in older women: The Women's Health Initiative. J Am Geriatr Soc2017;65(9):1924–1931.