Division of Endocrinology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
J Bone Miner Res. 2013 Jun;28(6):1319-27. doi: 10.1002/jbmr.1864.
Management of women discontinuing bisphosphonates after 3 to 5 years of treatment is controversial. Little is known about how much bone mineral density (BMD) is lost after discontinuation or whether there are risk factors for greater rates of bone loss post-discontinuation. We report patterns of change in BMD and prediction models for the changes in BMD in postmenopausal women during a 5-year treatment-free period after alendronate (ALN) therapy. We studied 406 women enrolled in the Fracture Intervention Trial (FIT) who had taken ALN for a mean of 5 years and were then enrolled in the placebo arm of the FIT Long-Term Extension (FLEX) trial for an additional 5 years, describing 5-year percent changes in total hip, femoral neck, and lumbar spine BMD over the treatment-free period. Prediction models of 5-year percent changes in BMD considered all linear combinations of candidate risk factors for bone loss such as BMD at the start of the treatment-free period, the change in BMD on ALN, age, and fracture history. Serum for three markers of bone turnover was available in 76 women, and these bone turnover markers were included as candidate predictors for these 76 women. Mean 5-year BMD changes were -3.6% at the total hip, -1.7% at the femoral neck, and 1.3% at the lumbar spine. Five-year BMD losses of >5% were experienced by 29% of subjects at the total hip, 11% of subjects at the femoral neck, and 1% of subjects at the lumbar spine. Several risk factors such as age and BMI were associated with greater bone loss, but no models based on these risk factors predicted bone loss rates. Although about one-third of women who discontinued ALN after 5 years experienced >5% bone loss at the total hip, predicting which women will lose at a higher rate was not possible.
在接受 3 至 5 年的治疗后停止使用双膦酸盐的女性的管理存在争议。人们对停药后骨密度（BMD）的损失量以及是否存在停药后骨质流失率更高的风险因素知之甚少。我们报告了阿仑膦酸钠（ALN）治疗 5 年后 5 年无治疗期内绝经后妇女 BMD 变化模式和 BMD 变化预测模型。我们研究了 406 名参加骨折干预试验（FIT）的女性，她们接受 ALN 治疗的平均时间为 5 年，然后参加 FIT 长期扩展（FLEX）试验的安慰剂组，在无治疗期内共 5 年，描述了无治疗期内总髋部、股骨颈和腰椎 BMD 的 5 年百分比变化。BMD 5 年百分比变化的预测模型考虑了与骨质流失相关的所有线性组合候选风险因素，例如无治疗期开始时的 BMD、ALN 治疗期间的 BMD 变化、年龄和骨折史。76 名女性的血清中有三种骨转换标志物，这些骨转换标志物被纳入这 76 名女性的候选预测因子。总髋部的平均 5 年 BMD 变化为-3.6%，股骨颈为-1.7%，腰椎为 1.3%。29%的受试者总髋部、11%的受试者股骨颈和 1%的受试者腰椎 5 年 BMD 丢失>5%。一些风险因素，如年龄和 BMI，与更大的骨质流失相关，但没有基于这些风险因素的模型预测骨质流失率。尽管大约三分之一在接受 5 年 ALN 治疗后停止使用的女性总髋部骨丢失>5%，但预测哪些女性会以更高的速度丢失是不可能的。
