Dennis M. Black, PhD Professor and Division Head, Clinical Trials & Multicenter Studies Department of Epidemiology and Biostatistics University of California, San Francisco

Bisphosphonates: Fragile Broken Bones vs Atypical Fractures

MedicalResearch.com Interview with:

Dennis M. Black, PhD Professor and Division Head, Clinical Trials & Multicenter Studies Department of Epidemiology and Biostatistics University of California, San Francisco

Dr. Black

Dennis M. Black, PhD
Professor and Division Head, Clinical Trials & Multicenter Studies
Department of Epidemiology and Biostatistics
University of California, San Francisco

MedicalResearch.com: What is the background for this study?

Response: Bisphosphonate and other osteoporosis medications are extremely effective in reducing spine, hip and other osteoporotic fractures by as much as 70%.  As you likely know, hip fractures in particular can be devastating to an older person, increasing mortality and limiting the ability to live independently.  The first bisphosphonates became available in about 1997 and are now generic, very inexpensive and have few side effects.  They are used by millions around the world.

Atypical femur fractures have received a lot of publicity and have created fears among clinicians and patients and have resulted in greatly decreased use of these effective medications.  However, despite their huge impact, previous studies have been flawed in important ways.  

MedicalResearch.com: What are the main findings? 

Response: The main findings were that atypical fractures are extremely rare compared to the much more common hip and other osteoporotic fractures that can be prevented (see figure 1 and especially 2).

We also were reassured to find that the AFF risk was strongly associated with duration of use beyond about 5 years and was quickly and dramatically reduced after discontinuing. This strongly supports the concept of a “drug holiday”, a temporary discontinuation of bisphosphonates after 5 years or so of treatment.

It was surprising to find that older age and lower bone density, strong risk factors for hip and spine fractures, were not strongly associated with AFF which is important in choosing women to most benefit from treatment.

There was a much higher risk among women of Asian ancestry than Caucasians and others which was not impacted by adjustment for other factors such as weight, height, etc.  The benefit risk balance is extremely favorable in Caucasians (figure 2) but less so in Asians suggesting we may have to reserve treatment and long term treatment in Asians for those at higher risk of hip or spine fractures.

MedicalResearch.com: What should readers take away from your report?

Response: We could hope that clinicians and patients can take away the following:

    1. The benefits of bisphosphonates and other osteoporosis treatments, including the reduction of the devastating consequences of hip and other fractures  far, far outweigh the risks of atypical fractures.
    2. Risks of atypical femur fracture can be greatly reduced by using drug holidays in many patients.
    3. The benefits far outweigh risks in Caucasians and other race groups that we studied other than Asians, where the balance was more modest. Clinicians might want to focus osteoporosis treatment in Asian women to those at higher risk hip and spine fractures, for example those older than 70 or with very low bone density. Shorter duration of therapy and use of a drug holiday might be particularly valuable in Asian patients.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

  • More research on the pathogenesis of atypical fractures including why they are more common in Asian-Americans
  • Development of risk algorithms for atypical femur fracture that can be used to guide clinical decisions about starting bisphosphonates and taking drug holidays in individual patients.  The risks of atypical femur fracture can then be balanced against the benefits for other fracture reductions in individual patients.
  • More research on occurrence of atypical fractures with osteoporosis treatments other than oral bisphosphonates.

My disclosures are in the article.   

Citations:

Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates

Dennis M. Black, Ph.D., Erik J. Geiger, M.D., Richard Eastell, M.D., Eric Vittinghoff, Ph.D., Bonnie H. Li, M.S., Denison S. Ryan, M.P.H., Richard M. Dell, M.D., and Annette L. Adams, Ph.D.
August 20, 2020
N Engl J Med 2020; 383:743-753
DOI: 10.1056/NEJMoa1916525

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Aug 19, 2020 @ 9:52 pm 

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