Long-term bisphosphonate treatment may increase risk of some fractures in older women

Older women who took bisphosphonates for more than five years had a higher risk of subtrochanteric and femoral shaft fractures than those who didn't, but the absolute risk was low, a new study reports.

Researchers performed a population-based, nested case-control study to determine the relationship between bisphosphonate use and fractures in a Canadian cohort. The study included women 68 years of age and older who had begun taking oral bisphosphonates between April 1, 2002 and March 31, 2008. Case-patients hospitalized with subtrochanteric or femoral shaft fractures were matched with five or fewer controls who had taken bisphosphonates but did not have fractures. The median age of both case-patients and controls was 83 years. The study's main outcome measure was the association between hospitalization for subtrochanteric or femoral shaft fracture and time taking bisphosphonates. To test specificity, the authors also examined the association between bisphosphonate exposure and femoral neck or intertrochanteric fractures. The study results appear in the Feb. 23 Journal of the American Medical Association.

Participants were followed until first subtrochanteric or femoral shaft fracture, death, or the end of the study (March 31, 2009). A total of 719 women had subtrochanteric or femoral shaft fractures after starting bisphosphonate therapy. In addition, 9,723 had intertrochanteric or femoral neck fractures, which are commonly associated with osteoporosis. Women who had taken bisphosphonates for five years or more had a higher risk of subtrochanteric or femoral shaft fracture (adjusted odds ratio, 2.74, 95% CI, 1.25 to 6.02) than women who had taken them transiently, or for less than 100 days. However, among 52,595 women who had taken bisphosphonates for at least five years, only 71 (0.13%) had a subtrochanteric or femoral shaft fracture within the next year and just 117 (0.22%) had one within the next two years. Long-term use of bisphosphonates was associated with lower risk of usual osteoporotic fractures (adjusted odds ratio, 0.76, 95% CI, 0.63 to 0.93) than transient use.

The authors noted that their results could have been affected by potential residual confounding and misclassification of bisphosphonate exposure, among other limitations. They concluded that at least five years of bisphosphonate therapy was associated with a higher risk for subtrochanteric or femoral shaft fractures in older women but also noted that the absolute risk for such fractures appeared low. They wrote that based on their findings, individual fracture risk should be assessed before long-term bisphosphonate therapy is initiated and that the therapy may not be warranted in patients whose risk is relatively low. “It may be appropriate to consider a drug holiday for selected patients, particularly as the cumulative duration of bisphosphonate therapy surpasses 5 years,” they said.