WHI data shed light on risks of long-term bisphosphonate use

Analysis of data from the Women’s Health Initiative study adds to concerns about potential risks of long-term use of bisphosphonates in elderly women. The findings, published in The Journal of the American Geriatrics Society, reflect outcomes in a large group of patients at high risk of fracture, many of whom had taken the drugs for at least 10 years.

Women in the retrospective cohort had an average age of 80 years and had used bisphosphonates for at least 2 years, as self-reported on a 2008-2009 medication inventory. The 2-year mark was chosen as a reference because that duration of use has been associated with lower fracture risk. Follow-up on the group was from 3.7 ± 1.2 years. Women who had used other medications that affect bone metabolism, including calcitonin, selective estrogen reuptake inhibitors, parathyroid hormone, and aromatase inhibitors, were excluded. The cohort also did not include patients who reported using estrogen within 5 years before the medication inventory or those who had discontinued bisphosphonates but resumed them.

For outcomes, the researchers looked at annual rates of hip, clinical vertebral, wrist or forearm fracture, and any clinical fracture. They also used multivariate Cox proportional hazards models to determine whether there was an association between use of bisphosphonates for 3 to 5; 6 to 9; or 10 to 13 years and fracture, compared with use for 2 years.

The multivariate-adjusted analysis showed that using bisphosphonates for 10 to 13 years was associated with higher risk of clinical fracture than 2 years of use (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.07 to 1.57). The risk persisted when the analysis was limited to women who had a prior fracture (HR = 1.30, 95% CI = 1.01-1.67) and those with no history of cancer (HR = 1.36, 95% CI = 1.10-1.68). Among patients on bisphosphonates for 10 to 13 years, risk was higher for hip (HR = 1.66, 95% CI = 0.81-3.40) and clinical vertebral fractures (HR = 1.65, 95% CI = 0.99-2.76) although the associations for this dosage duration were not statistically significant for any site-specific fracture.

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The researchers noted that their study looked at the association between fracture risk and bisphosphonate use “in more high-risk, older female long-term bisphosphonate users than any previous study.” They theorized that the findings may be explained by “biological changes in bone during long-term bisphosphonate use…including oversuppression of the bone remodeling process, which may damage bone.”

The study’s strengths include the large sample, which incorporated long-term users of the drugs and women who had taken them for up to 13 years. The authors also adjusted for 5-year hip fracture risk score and for many participant characteristics predictive of fracture risk.

REFERENCE

1. Drieling R, LaCroix A, Beresford S, et al. Long-Term Oral Bisphosphonate Therapy and Fractures in Older Women: The Women’s Health Initiative. J Am Geriatr Soc. 2017; 1532-5415. 10.1111/jgs.14911.