Study Links Long-term Use of Bisphosphonates to Unusual Fractures

February 23, 2011

Women who take bisphosphonates for five years or more may be at higher risk of certain kinds of fractures of their thigh bone.

Women who take bisphosphonates for osteoporosis for five years or more may be at higher risk of certain kinds of fractures of their thigh bone, a new study in the Journal of the American Medical Association has found.

However, the drugs do prevent hip fracture, and since the overall risk of thigh bone fractures caused by the drugs is low, women at high risk for hip and other osteoporosis-related fractures should not stop taking bisphosphonates. The study was conducted by researchers at St. Michael’s Hospital and the Institute for Clinical Evaluative Sciences in Toronto.

“Prolonged use of bisphosphonates is associated with rare and unusual fractures of the femur,” lead author Laura Park-Wyllie, PharmD, a pharmaceutical safety and outcomes researcher at St. Michael’s, said in a press release.

“But the proven benefit of these drugs for the much more common fractures of osteoporosis usually outweighs the harm, especially in the initial years of treatment for osteoporosis. Women with osteoporosis, at high risk for osteoporotic fractures, should not stop taking bisphosphonate therapy because of the small risk of these thigh fractures.”

Typical hip fractures caused by osteoporosis occur in the upper part of the femur close to the hip joint and are an important cause of disability, need for long-term care, and even death in the elderly. The risk of these kinds of fractures is reduced by bisphosphonate treatment, which was confirmed by this study.

But the study found that atypical fractures lower down from the hip and closer to the middle of the femur occurred more than 2.5 times as often in women who had taken bisphosphonates for more than five years than short-term users of the drug.

Park-Wyllie said the study was prompted by an increasing number of reports of thigh bone fractures among older women who have taken the drugs sold as Fosamax (alendronate), Actonel (risedronate), or Didrocal (etidronate/calcium) for five years or more and by conflicting findings from small, observational studies.

Park-Wyllie’s study is the largest assessment of the issue to date. The researchers identified 205,466 women over age 68 who were prescribed bisphosphonates between 2002 and 2008. Of those, 716 women (0.35%) had a fracture of the femur. These women were compared to other women of similar ages who had also been prescribed the drugs but who did not have femur fractures.

“Our study estimated that the risk of fractures to the femur was 0.13% for women entering their sixth year on the drug, or just over one in 1,000,” Park-Wyllie said. “Use of bisphosphonates for less than five years was not associated with a significant risk of thigh fractures.”