Is Long-term Survival Associated With the Use of Nitrogen-containing Bisphosphonates?

Is Long-term Survival Associated With the Use of Nitrogen-containing Bisphosphonates? Posted By:
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In the January issue of Osteoporosis International, there was an article entitled, "Mortality Risk Reduction Differs According to Bisphosphonate Class: A 15-Year Observational Study." This was a prospective cohort study of bisphosphonate users matched to non-users from 1995 to 2013. Study participants were from nine regional centers in Canada.

The study paired 2048 women and 308 men on bisphosphonates and 1970 women and 1794 men on no bisphosphonates for osteoporosis. They were separated in to three groups: nitrogen bisphosphonates (n-BP; alendronate and risedronate); non n-BP users (etidronate); and non-bisphosphonates users in patients with osteoporosis. The conclusion noted that there were significantly lower overall mortality rates among those treated with n-BP when compared with no mortality risk reduction among those receiving etidronate or no treatment.

N-BPs are more potent and we know from the zoledronic acid randomized controlled trials (RCT) that they confer at 28% lower mortality rate after hip fracture, as seen in the HORIZON Recurrent Fracture Trial.

To what do we owe this significant decline in overall mortality? Could it be the more obvious mechanism of a lower rate of bone loss with the more potent n-BP alendronate and risedronate? When analyzed in the RCT of zoledronic acid in women with hip fractures there was only an 8% mortality risk reduction attributable to a subsequent fracture. Could the reduction in mortality be attributable to something even more tantalizing and consistent with emerging evidence that n-BPs may have an anti-inflammatory effect and anti-cancer effect?

This review strongly suggests that our narrative should include the favorable outcomes of reduction in all-cause mortality/increased survival as an educational point when informing our patients with osteoporosis of the risks and benefits of this class of medications. I am hopeful that future analysis will include other osteoporosis medications such as the RANKL inhibitor, denosumab, and the two anabolics, teriparatide and abaloparatide. I am hopeful that our PA and NP colleagues will use this significant reduction in all-cause mortality as a motivator for our patients to take these medications and remain compliant over time.

References
  • Bliuc D, Tran T, van Geel T, et al. Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study. Osteoporos Int. 2019. Epub ahead of print.
  • Clezardin P, Ebetino FH, Fournier PG. Bisphosphonates and cancer-induced bone disease: beyond their antiresorptive activity. Cancer Res. 2005;65:4971-4974.
  • Colon-Emeric CS, Mesenbrink P, Lyles KW, et al. Potential mediators of the mortality reduction with zoledronic acid after hip fracture. J Bone Miner Res. 2010;25:91-97.
  • Conti L, Casetti R, Cardone M, et al. Reciprocal activating interaction between dendritic cells and pamidronate-stimulated gammadelta T cells: role of CD86 and inflammatory cytokines. J Immunol. 2005;174:252-260.
  • Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-1809.

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Filed under: Rheumatology

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