Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK.
J Bone Miner Res. 2019 Apr;34(4):632-642. doi: 10.1002/jbmr.3641. Epub 2019 Jan 23.
Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in osteoporosis trials. Numerous studies have been conducted since then, incorporating new therapies with different mechanisms of action and enrolling many more subjects. To extend these prior analyses, we conducted a meta-regression of 38 placebo-controlled trials of 19 therapeutic agents to determine the association between improvements in BMD and reductions in fracture risk. We used a linear model to examine the relationship between mean percent difference in BMD change between treatment and placebo groups and the logarithm of the relative risk. We found that greater improvements in BMD were strongly associated with greater reductions in vertebral and hip fractures but not nonvertebral fractures. For vertebral fracture, the r values for total hip, femoral neck, and lumbar spine BMD change were 0.56, 0.54, and 0.63, respectively (p ≤ 0.0002). For a 2% or 6% improvement in total hip BMD, we might expect a 28% or 66% reduction, respectively, in vertebral fracture risk. For hip fracture, the r values for total hip, femoral neck, and lumbar spine BMD change were 0.48 (p = 0.01), 0.42 (p = 0.02), and 0.22 (ns), respectively. For a 2% or 6% improvement in total hip BMD, we might expect a 16% or 40% reduction in hip fracture risk. In conclusion, our results extend prior observations that larger improvements in dual-energy X-ray absorptiometry (DXA)-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures. Although these results cannot be directly applied to predict the treatment benefit in an individual patient, they provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful surrogate endpoints for fracture in trials of new therapeutic agents. © 2019 American Society for Bone and Mineral Research.
15 年前进行的荟萃分析报告称，骨质疏松症试验中骨密度（BMD）的改善与椎体和非椎体骨折的减少有关。此后进行了许多研究，纳入了具有不同作用机制的新疗法，并招募了更多的受试者。为了扩展这些先前的分析，我们对 19 种治疗药物的 38 项安慰剂对照试验进行了元回归分析，以确定 BMD 改善与骨折风险降低之间的关联。我们使用线性模型来研究治疗组和安慰剂组之间 BMD 变化的平均百分比差异与相对风险对数之间的关系。我们发现，BMD 的更大改善与椎体和髋部骨折的更大减少密切相关，但与非椎体骨折无关。对于椎体骨折，总髋部、股骨颈和腰椎 BMD 变化的 r 值分别为 0.56、0.54 和 0.63（p≤0.0002）。对于总髋部 BMD 提高 2%或 6%，我们可能分别预期椎体骨折风险降低 28%或 66%。对于髋部骨折，总髋部、股骨颈和腰椎 BMD 变化的 r 值分别为 0.48（p=0.01）、0.42（p=0.02）和 0.22（ns）。对于总髋部 BMD 提高 2%或 6%，我们可能分别预期髋部骨折风险降低 16%或 40%。总之，我们的结果扩展了先前的观察结果，即双能 X 射线吸收法（DXA）基于 BMD 的更大改善与更大的骨折风险降低相关，特别是对于椎体和髋部骨折。尽管这些结果不能直接应用于预测个体患者的治疗益处，但它们提供了有力的证据，表明骨质疏松症治疗中 BMD 的改善可能是新治疗药物试验中骨折的有用替代终点。
