Bauer Douglas C, Schwartz Ann, Palermo Lisa, Cauley Jane, Hochberg Marc, Santora Art, Cummings Steven R, Black Dennis M
Department of Medicine, University of California, San Francisco2Department of Epidemiology and Biostatistics, University of California, San Francisco.
Department of Epidemiology and Biostatistics, University of California, San Francisco.
JAMA Intern Med. 2014 Jul;174(7):1126-34. doi: 10.1001/jamainternmed.2014.1232.
Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established.
To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years.
DESIGN, SETTING, AND PARTICIPANTS: The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years.
Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover.
During 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]).
Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended.
clinicaltrials.gov Identifier: NCT00398931.
越来越多的人考虑在3至5年后停用双膦酸盐治疗，但停用后监测骨折风险的方法尚未确立。
测试预测在4至5年后停用阿仑膦酸盐治疗的女性骨折风险的方法。
设计、设置和参与者：前瞻性骨折干预试验长期扩展（FLEX）研究在1998年至2003年期间，将61至86岁、先前接受过4至5年阿仑膦酸盐治疗的绝经后女性随机分为继续接受5年阿仑膦酸盐治疗组或安慰剂组；本分析仅包括安慰剂组。在开始使用安慰剂时（FLEX基线）以及随访1至3年后，测量髋部和脊柱的双能X线吸收法（DXA）。在FLEX基线以及1年和3年后，测量两种骨转换的生化标志物，即尿1型胶原交联N-端肽（NTX）和血清骨特异性碱性磷酸酶（BAP）。
在DXA或骨转换随访测量后发生的有症状的脊柱和非脊柱骨折。
在5年的安慰剂治疗期间，437名女性中有94名（22%）经历了1次或更多次有症状的骨折；82名在1年后发生骨折。髋部DXA、NTX和BAP的1年变化与随后的骨折风险无关，但停药时年龄较大和髋部DXA较低与骨折风险增加显著相关（基线股骨颈DXA最低三分位数与其他两个三分位数相比，相对危险比为2.17[95%CI，1.38 - 3.41]；全髋DXA相对危险比为1.87[95%CI，1.20 - 2.92]）。
在4至5年后停用阿仑膦酸盐治疗的绝经后女性中，停药时的年龄和髋部骨密度可预测随后5年内的临床骨折。停药1年后的DXA随访测量以及停药1至2年后的BAP或NTX测量与骨折风险无关，不建议进行。
clinicaltrials.gov标识符：NCT00398931。
