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Long-term oral bisphosphonate use in relation to fracture risk in postmenopausal women with breast cancer: findings from the Women's Health Initiative

Drieling, Rebecca L. MPH, PhD; LaCroix, Andrea Z. PhD, MPH; Beresford, Shirley A.A. PhD, MS; Boudreau, Denise M. PhD; Kooperberg, Charles PhD; Chlebowski, Rowan T. MD, PhD; Gass, Margery MD; Crandall, Carolyn J. MD, MS; Womack, Catherine R. MD; Heckbert, Susan R. MD, PhD

doi: 10.1097/GME.0000000000000696
Original Articles
Editorial

Objective: The aim of the study was to examine the association of long-term oral bisphosphonate use, compared with short-term use, with fracture risk among postmenopausal women with breast cancer.

Methods: We studied 887 postmenopausal women who were enrolled to the Women's Health Initiative from 1993 to 1998, diagnosed with breast cancer after enrollment, and reported current oral bisphosphonate use of 2 years or more on a medication inventory administered in 2008 to 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 to 7 years and 8 or more years of bisphosphonate use with 2 to 3 years of use.

Results: On average, women were 76 years of age and were followed for 3.7 (SD 1.1) years. There were 142 clinical fractures. 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 to 3 years of use (hazard ratio, 1.67 [95% CI, 1.06-2.62]). There was no significant association of 4 to 7 years of use with fracture.

Conclusions: Bisphosphonate use of 8 or more years was associated with higher risk of any clinical fracture compared with 2 to 3 years of use. Our findings raise concern about potential harm or decreased effectiveness of long-term bisphosphonate use on fracture risk. The findings warrant confirmatory studies.

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1University of Washington School of Public Health, Seattle, WA

2Division of Epidemiology and Department of Family and Preventive Medicine, University of California San Diego, San Diego, CA

3Fred Hutchinson Cancer Research Center, Seattle, WA

4Group Health Research Institute, Group Health Cooperative, Seattle, WA

5University of Washington School of Pharmacy, Seattle, WA

6Los Angeles Biomedical Research Institute at Harbor–University of California Los Angeles Medical Center, Torrance, CA

7The North American Menopause Society, Cleveland, OH

8David Geffen School of Medicine at University of California, Los Angeles, CA

9University of Tennessee Health Science Center, Memphis, TN.

Address correspondence to: Rebecca L. Drieling, MPH, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M3-A410, Seattle, WA 98109. E-mail: drieling@uw.edu

Received 12 December, 2015

Revised 14 April, 2016

Accepted 14 April, 2016

Funding/support: The present article was partially supported by the National Cancer Institute Biobehavioral Cancer Prevention and Control Training Program at the University of Washington (grant R25CA092408). The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.

Financial disclosure/conflicts of interest: Conception or design, acquisition of data, and data analysis: A.Z.L., D.M.B., R.L.D., S.A.A.B., and S.R.H. Drafted manuscript: R.L.D. Supervision: A.Z.L., C.R.W., D.M.B., and S.A.A.B. Administrative, technical, or material support: R.T.C. Critical manuscript revision of manuscript for important intellectual content and interpretation of data: R.L.D., A.Z.L., S.A.A.B., D.M.B., C.K., R.T.C., M.G., C.J.C., C.R.W., and S.R.H. A.L. serves on Scientific Advisory Boards for Amgen and Sermonix, and served as a one-time consultant for Pfizer in the past 12 months. R.C. is a consultant for Novartis, Amgen, Genentech, Pfizer, and Novo Nordisk and serves on the speakers Bureau for Novartis and Genentech. All other authors state they have no conflicts of interest.

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© 2016 by The North American Menopause Society.