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The latest report from the Women’s Health Initiative (WHI) study combines results from the two randomized, controlled trials and the observational study [1]. The aim of the study was to examine the association of long-term oral bisphosphonate use, compared with short-term use, with clinical fracture risk among postmenopausal women with breast cancer. Participants were 887 postmenopausal women who were enrolled to the WHI from 1993 to 1998, diagnosed with breast cancer after enrollment, and who reported current oral bisphosphonate use of 2 years or more on a medication inventory administered in 2008–2009. The outcome of any clinical fracture was ascertained by self-report on an annual study form; a subset of fractures was confirmed with medical records. Women were followed from completion of the medication inventory until 2014. The association between duration of bisphosphonate use reported on the medication inventory and fracture was estimated using multivariate Cox proportional hazards survival models that compared 4–7 years and 8 or more years of bisphosphonate use with 2–3 years of use.

There were 142 clinical fractures reported. In the multivariate-adjusted analysis for fracture risk factors, 8 or more years of bisphosphonate use was associated with higher risk of fracture compared with 2–3 years of use (hazard ratio 1.67; 95% confidence interval 1.06–2.62). There was no significant association of 4–7 years of use with fracture. It was concluded that bisphosphonate use of 8 or more years was associated with higher risk of any clinical fracture compared with 2–3 years of use. The authors raise concern about potential harm or decreased effectiveness of long-term bisphosphonate use on fracture risk. They caution, though, that the findings warrant confirmatory studies.


  • Tobie J. de Villiers
    Department of Gynaecology, Stellenbosch University, South Africa


  1. Drieling RL, LaCroix AZ, Beresford SA, et al. Long-term oral bisphosphonate use in relation to fracture risk in postmenopausal women with breast cancer: findings from the Women’s Health Initiative. Menopause 2016 July 18. Epub ahead of print
  2. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006;296:2927-38
  3. Black DM, Reid IR, Boonen S, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the Horizon-pivotal Fracture Trial (PFT). J Bone Miner Res 2012;27:243-54
  4. Goss PE, Ingle JN, Pritchard KI, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med 2016; 375:209-19
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