Chapurlat R D, Palermo L, Ramsay P, Cummings S R
Department of Rheumatology and Bone Diseases and INSERM U403, E. Herriot Hospital, 69437 Lyon, France.
Osteoporos Int. 2005 Jul;16(7):842-8. doi: 10.1007/s00198-004-1770-7. Epub 2004 Dec 3.
It is commonly believed that the response to treatment in patients on alendronate is proportional to the increase in bone mineral density (BMD), and that those who lose BMD during treatment might not respond to treatment. In the Fracture Intervention Trial 6,459 women were randomly assigned to treatment with alendronate or placebo; BMD was measured annually, and new spine fractures were assessed by lateral spine films, taken at baseline and end of follow-up. Among subjects who took at least 70% of the study drug (5,220 women), we compared reductions in risk of spine fractures at end of follow-up (3 or 4 years) within various levels of change in total hip and spine BMD after 1 and 2 years of treatment, after adjustment for differences in characteristics between the treatment and control groups. Women "losing" BMD at the lumbar spine (0% to 4%) while on alendronate had a reduction of 60% in vertebral fracture risk [OR = 0.40 (0.16, 0.99)] compared to their counterparts in the placebo group. The few women that lost more than 4% did not have a significant benefit [OR = 0.15 (0.02, 1.29)]. Those who "gained" BMD (0% to 4%) during treatment had a reduction in risk of 51% [OR = 0.49 (0.30, 0.78)]. Similarly, women who "lost" total hip BMD (0% to 4%) during the first year on alendronate had a 53% decreased risk of vertebral fracture compared to their controls taking placebo [OR = 0.47 (0.27, 0.81)], whereas those "gaining" BMD (0% to 4%) had a comparable risk reduction [OR = 0.49 (0.34, 0.71)]. This was not observed for the few women who lost more than 4% [OR = 0.61 (0.11, 3.45)]. Patients who lost BMD at both the hip and spine were not protected by alendronate. Among patients who adhere to treatment with alendronate, even those who lose BMD benefit from a substantial reduction in risk of vertebral fracture. So, the reduction in bone turnover induced by alendronate might be more important than BMD changes. The few women who lose the most BMD (more than 4% per year) might not benefit from the treatment.
人们普遍认为，接受阿仑膦酸盐治疗的患者对治疗的反应与骨矿物质密度（BMD）的增加成正比，并且那些在治疗期间骨密度降低的患者可能对治疗无反应。在骨折干预试验中，6459名女性被随机分配接受阿仑膦酸盐或安慰剂治疗；每年测量骨密度，并通过在基线和随访结束时拍摄的脊柱侧位片评估新的脊柱骨折情况。在至少服用了70%研究药物的受试者（5220名女性）中，我们在调整了治疗组和对照组之间特征差异后，比较了治疗1年和2年后全髋和脊柱骨密度不同变化水平下随访结束时（3年或4年）脊柱骨折风险的降低情况。服用阿仑膦酸盐期间腰椎骨密度“降低”（0%至4%）的女性与安慰剂组的女性相比，椎体骨折风险降低了60%[比值比（OR）=0.40（0.16，0.99）]。少数骨密度降低超过4%的女性没有显著获益[OR = 0.15（0.02，1.29）]。治疗期间骨密度“增加”（0%至4%）的女性风险降低了51%[OR = 0.49（0.30，0.78）]。同样，服用阿仑膦酸盐第一年全髋骨密度“降低”（0%至4%）的女性与服用安慰剂的对照组相比，椎体骨折风险降低了53%[OR = 0.47（0.27，0.81）]，而骨密度“增加”（0%至4%）的女性风险降低程度相当[OR = 0.49（0.34，0.71）]。少数骨密度降低超过4%的女性未观察到这种情况[OR = 0.61（0.11，3.45）]。髋部和脊柱骨密度均降低的患者未受到阿仑膦酸盐的保护。在坚持服用阿仑膦酸盐治疗的患者中，即使是那些骨密度降低的患者也从椎体骨折风险的大幅降低中获益。因此，阿仑膦酸盐引起的骨转换降低可能比骨密度变化更重要。少数骨密度降低最多（每年超过4%）的女性可能无法从治疗中获益。
