Review Examines Relationship Between Atypical Femur Fractures and Bisphosphonates

A paper recently published in Endocrine Reviews covers atypical femur fractures (AFFs) and examines their relationship with bisphosphonates (BPs), as well as prevention and treatment of these rare but devastating bone breaks.

The review, by Dennis M. Black, PhD, of the University of California, San Francisco, et al, points out that BPs have been the mainstay in the treatment of osteoporosis since the early 1990s, but about 2006, AFFs emerged as a potential side effect to these drugs. Organizations like the American Society of Bone and Mineral Research and the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International Osteoporosis Foundation released position papers and statements, and the FDA held a hearing on the safety of BPs in 2010. This all eroded patient and physician trust in these drugs, which led to about a 50% decrease in their usage from 2007 to 2012.

However, AFFs remain extremely rare, and the benefits gained from BPs used when treating more common fractures far outweigh the risks of AFFs. “Under the most likely set of assumptions about AFF risk [relative risk of 1.7 for any BP use], upon treating 10,000 osteoporotic women for 3 years, 1,000 fractures, including 110 hip fractures, would be prevented while causing only 0.08 AFFs,” the authors write. “Stated another way, for one AFF associated with 3 years of BP treatment, ∼1200 fractures (including about 130 hip and 850 vertebral fractures) would be prevented.”

The authors continue by writing that there remains significant controversy between the use of osteoporosis therapies and duration of therapy to the risk of AFFs and about the pathophysiology of AFFs. “This review discusses the current evidence regarding their epidemiology and pathogenesis, clinical implications, and recommendations, and it identifies areas where future research is needed,” they write.

The review covers a lot, but the authors write that there seem to be specific risk factors that could put patients at a higher risk for AFFs, including bone geometry, race, and conditions like diabetes. But since the mechanisms for these risk factors aren’t well understood, they should be further studied.

The authors also write that temporary drug holidays after three to five years of therapy are appropriate for BPs in patients at low risk of fracture. In fact, there are some data that show a drug holiday can decrease AFF risk, which means an improved benefit/risk ratio. Still, the authors write, “[m]ore research about the impact of temporary BP drug holidays on AFF risk is needed.”

“In conclusion,” the authors write, “AFFs can be devastating, but even under the most pessimistic assumptions, the benefit/risk ratio is highly positive for BPs, particularly during 3 to 5 years of use. As understanding of AFFs increases, it is becoming increasingly possible to maximize BP benefits while minimizing AFF risk.”

Read more about pharmacological management of osteoporosis in postmenopausal women in the Endocrine Society’s recently published Clinical Practice Guideline.

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