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Osteoporotic Fracture and Bisphosphonates: What are the Long-Term Risks?

Researchers use data from large-scale postmenopausal studies to determine whether long-term bisphosphonate use is a good solution for preventing osteoporotic fractures.

Osteoporosis is frequently associated with an increased risk of fracture due to a reduction in bone mineral density.

About half of women over 50 years old are expected to experience an osteoporotic fracture.

Bisphosphonates, which suppress the breakdown and remodeling of bone tissue, are the most commonly prescribed osteoporotic medication type.

However, review studies have not found conclusive evidence that long-term bisphosphonate use is effective in preventing fractures in women with osteoporosis.

The Food and Drug Administration (FDA) has recommended that individuals undergo periodic evaluations before continuing bisphosphonate therapy, based on results from smaller-scale studies.

Due to the need for larger-scale analysis, a team of American researchers retroactively examined data from the Women’s Health Initiative (WHI), a long-term study of women’s health dating back to 1993.

The WHI consists of clinical trials and observational studies measuring the effects of hormone and dietary interventions on the incidence of heart disease, cancer, and fractures in postmenopausal women.

Their work was published in the Journal of the American Geriatric Society.

Researchers retrieved data regarding the annual incidence of fractures from women who had reported at least two years of bisphosphonate use.

A total of 5,120 women were included in the analysis, with an average follow-up period of 3.7 years.

The authors performed statistical analyses on the association between fracture rates and bisphosphonate use while adjusting for confounding variables such as age, physical activity, general health rating, and more.

They discovered that older women who had taken bisphosphonates for 10 to 13 years had higher rates of clinical fracture compared to those who had only taken them for two years.

On the other hand, women who had taken bisphosphonates for 3 to 5 and 6 to 9 years were not associated with a significant risk of fracture.

The reason for these findings is not entirely clear, but the authors suspect that the inhibition of bone tissue breakdown associated with bisphosphonate use may lead to long-term structural changes that actually increase the risk of fracture.

In particular, the suppression of the remodeling process for damaged bones is thought to increase their brittleness.

One of the main limitations of this study is the self-reported nature of some of the data.

Bisphosphonate use was self-reported through mailed forms, and not all fractures were confirmed by reviewing medical records.

However, the researchers maintain that the accuracy of the data was supported by previous validity studies which found a high degree of agreement between self-reported data and clinical or pharmacy records.

These results raise concerns about the safety of long-term bisphosphonate use, suggesting a re-evaluation of clinical recommendations of up to 10 years of bisphosphonate use.

Further research is recommended to develop guidelines for the optimal use of bisphosphonates to prevent osteoporotic fractures.

Written by Agustin Dominguez Iino, BSc

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Reference: Drieling RL et al. Long-Term Oral Bisphosphonate Therapy and Fractures in Older Women: The Women’s Health Initiative. J Am Geriatr Soc. 2017 Sep;65(9):1924-1931. doi: 10.1111/jgs.14911. Epub 2017 May 29.

Adriano Vissa PhD Candidate
Adriano Vissa PhD Candidate
Adriano completed his Ph.D. in Biochemistry and Biomedical Engineering at the University of Toronto, where he is currently a Postdoctoral Research Fellow. His research involved the technical development of super-resolution fluorescence imaging systems and their application to structural areas of interest in cell biology. Adriano has a keen interest in knowledge translation and enjoys communicating scientific advances to the public via Medical News Bulletin. In his spare time, Adriano enjoys playing hockey, strumming his guitar and creating crayon masterpieces with his baby daughter.
  1. Thanks for your comment about how there are lots of risks for fractures when you get to the ages 50 and older. I didn’t know that it came because bone tissue breaks down easily. My mother is looking into postmenopausal fracture treatments; I’ll pass this post on to her.


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