Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents
Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents
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DOI：
10.1210/jc.87.4.1586
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发表时间：
2002-04-01
影响因子：
5.8
通讯作者：
Ross, PD
中科院分区：
文献类型：
--
作者：
Hochberg, MC;Greenspan, S;Ross, PD
一些（但不是全部）抗骨吸收药物已被证明可以降低非椎骨骨折的风险。与其他药物相比，显著降低非椎骨骨折风险的药物似乎也能使骨矿物质密度（BMD）平均增加，并使骨转换的生化标志物（BMD）减少。为了检查抗骨吸收治疗期间BMD增加和BMD降低与非椎骨骨折风险降低的相关程度，我们对所有在绝经后骨质疏松症（即既往椎骨骨折或低BMD）妇女中进行的抗骨吸收药物随机、安慰剂对照试验进行了荟萃分析，并提供了相关数据。总共确定了具有可用数据的IS此类试验，包括在69，369名女性年随访期间发生非椎骨骨折的2，415名女性。Poisson回归用于估计第一年及以上BMD或BMD变化之间的相关性。所有试验中非椎骨骨折风险的所有降低（与安慰剂组相比）。BMD的较大增加和BMD的较大降低与非椎骨骨折风险的较大降低显著相关。例如，1年时脊柱BMD每增加1%，非椎骨骨折风险降低8%（P = 0.02）。髋部的平均BMD变化小于脊柱，但对骨折风险的预测净效应是相同的;一种药物在1年内使脊柱BMD增加6%，可使非椎骨骨折风险降低约39%，而一种药物在1年内使髋部BMD增加3%，可使非椎骨骨折风险降低约46%。研究结果还预测，再吸收减少70%将使风险降低40%，形成减少50%将使风险降低44%。似乎BMD或BMD的变化能够解释治疗的效果，因为治疗的单独变量在任何模型中均不具有独立显著性。这些数据表明，脊柱和髋部BMD的较大增加以及骨形成和骨吸收的较大减少与非椎骨骨折风险的较大降低相关。抗骨吸收药物不能使BMD显著增加或BMD显著降低，似乎不能也不会降低非椎骨骨折的风险。
Some, but not all, antiresorptive agents have been shown to reduce the risk of nonvertebral fractures. Agents that significantly reduced nonvertebral fracture risk also appear to produce larger mean increases in bone mineral density (BMD) and reductions in biochemical markers (BCM) of bone turnover, compared with other agents. To examine the extent to which increases in BMD and reductions in BCM during antiresorptive therapy are associated with reductions in risk of nonvertebral fractures, we performed a meta-analysis of all randomized, placebo-controlled trials of antiresorptive agents conducted in postmenopausal women with osteoporosis (i.e. prior vertebral fracture or low BMD) with available relevant data. A total of IS such trials with usable data were identified, including a total of 2,415 women with incident nonvertebral fractures over 69,369 women-years of follow-up. Poisson regression was used to estimate the association between changes in BMD or BCM during the first year and over. all reductions in risk of nonvertebral fractures (vs. the placebo group) across all trials. Larger increases in BMD and larger reductions in BCM were significantly associated with greater reductions in nonvertebral fracture risk. For example, each 1% increase in spine BMD at 1 yr was associated with an 8% reduction in nonvertebral fracture risk (P = 0.02). Mean BMD changes at the hip were smaller than at the spine, but the predicted net effect on fracture risk was the same; an agent that increases spine BMD by 6% at 1 yr reduces nonvertebral fracture risk by about 39%, and an agent that increases hip BMD by 3% at 1 yr reduces nonvertebral fracture risk by about 46%. The results also predict that a 70% reduction in resorption BCM would reduce risk by 40%, and a 50% reduction in formation BCM would reduce risk by 44%. It appears that either BMD or BCM changes are able to explain the effect of treatment, because a separate variable for treatment was not independently significant in any models. These data demonstrate that larger increases in BMD at both the spine and hip and larger reductions in both formation and resorption BCM are associated with greater reductions in the risk of nonvertebral fractures. Antiresorptive agents that do not produce large increases in BMD or large reductions in BCM do not appear to and would not be expected to decrease the risk of nonvertebral fractures.