Drieling Rebecca L, LaCroix Andrea Z, Beresford Shirley A A, Boudreau Denise M, Kooperberg Charles, Chlebowski Rowan T, Gass Margery, Crandall Carolyn J, Womack Catherine R, Heckbert Susan R
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.
Menopause. 2016 Nov;23(11):1168-1175. doi: 10.1097/GME.0000000000000696.
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.
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.
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.
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.
本研究旨在探讨绝经后乳腺癌女性长期口服双膦酸盐（与短期使用相比）与骨折风险之间的关联。
我们研究了887名绝经后女性，她们于1993年至1998年参加了妇女健康倡议研究，入组后被诊断为乳腺癌，并在2008年至2009年进行的药物清单调查中报告当前口服双膦酸盐使用时间为2年或更长时间。通过年度研究表格中的自我报告确定任何临床骨折的结局；部分骨折通过病历进行确认。对女性从完成药物清单调查直至2014年进行随访。使用多变量Cox比例风险生存模型估计药物清单上报告的双膦酸盐使用持续时间与骨折之间的关联，该模型将4至7年和8年或更长时间的双膦酸盐使用与2至3年的使用进行比较。
女性平均年龄为76岁，随访时间为3.7（标准差1.1）年。共有142例临床骨折。在骨折风险因素的多变量调整分析中，与使用2至3年相比，使用双膦酸盐8年或更长时间与骨折风险较高相关（风险比，1.67 [95%置信区间，1.06 - 2.62]）。使用4至7年与骨折无显著关联。
与使用2至3年相比，使用双膦酸盐8年或更长时间与任何临床骨折风险较高相关。我们的研究结果引发了对长期使用双膦酸盐对骨折风险的潜在危害或有效性降低的担忧。这些发现需要进行验证性研究。
