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Long-Term Bisphosphonate Use Linked with Unusual Femur Fractures

According to a study published in the Journal of the American Medical Association, long-term use of the osteoporosis drugs known as bisphosphonates may increase the risk of unusual types of femur fractures. The risk of these unusual fractures remains low, however, and should be balanced against the established benefits of bisphosphonates, which include a reduction in the risk of hip fractures.

Osteoporosis—a condition characterized by low bone mass and deterioration of bone structure—affects an estimated 10 million Americans over the age of 50. Each year, roughly 1.5 million Americans will experience an osteoporosis-related bone fracture. These fractures commonly involve the wrist, hip, or spine, but can affect any part of the body.

Drugs that may be used to treat osteoporosis include bisphosphonates (such as Fosamax® [alendronate], Actonel® [risedronate], Boniva® [ibandronate], and Reclast® [zoledronic acid]), Prolia® (denosumab), calcitonin, estrogen, Evista® (raloxifene), and Forteo® (teriparatide). Treatment of osteoporosis reduces the risk of fracture, including hip fracture. Hip fractures occur in the upper part of the femur (the thigh bone) and are an important cause of disability and death in the elderly.

Although bisphosphonates reduce the risk of hip fractures, there have been reports among bisphosphonate users of unusual types of femur fractures known as “subtrochanteric” or “femoral shaft” fractures. These fractures occur lower down on the femur than hip fractures.

To explore whether the frequency of these unusual femur fractures varies by duration of bisphophonate use, researchers in Canada collected information about a large population of women (age 68 or older) who used oral bisphosphonates. Information was available for 716 women who experienced a subtrochanteric or femoral shaft fracture, and 9,723 women who experienced a hip fracture.

  • Compared with very short-term bisphosphonate use (less than 100 days), use of a bisphosphonate for five years or longer was linked with a more than two-fold increase in risk of subtrochanteric or femoral shaft fracture. The overall risk of these fractures remained quite low, however: among more than 52,000 women with at least five years of bisphosphonate use, 117 (0.22%) developed an unusual femur fracture within two years.
  • The study confirmed that longer-term bisphosphonate use decreased the risk of hip fracture. Use of a bisphosphonate for five years or longer reduced the risk of hip fracture by 24%.

These results suggest that long-term use of oral bisphosphonates may increase the risk of unusual types of femur fractures in older women, while decreasing the risk of more typical osteoporosis-related fractures.

In the discussion of the results, the researchers note “Importantly, the results of our study should not deter clinicians and patients from using bisphosphonates in appropriate patients. Our study confirms the known benefits of bisphosphonate treatment for typical osteoporotic fracture, and evidence suggests that bisphosphonate therapies are underused in individuals at high risk of fracture despite their established efficacy.”


U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004.

Park-Wyllie L, Mamdani MM, Juurlink DN et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011;305:783-789.

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