绝经后骨质疏松的治疗进展

骨质疏松最常见的骨折部位是椎体、髋、前臂和肱骨近端。抑制骨吸收药物是治疗绝经后骨质疏松的主要药物。最近的Meta分析显示，维生素D仅在补充钙剂的基础上才能降低髋骨骨折。激素替代治疗对降低非椎体骨折风险的疗效没有椎体骨折那么清楚。雷诺昔芬可降低椎体骨折和乳腺癌的几率，但不能预防髋骨骨折。双膦酸盐是治疗绝经后骨质疏松最常用的药物，目前双膦酸盐(阿仑膦酸钠, 伊班膦酸钠, 利塞磷酸钠, 唑来膦酸钠)降低椎体骨折的证据水平是最高的，其对照临床试验提示椎体骨折和非椎体骨折（包括髋骨骨折）风险可分别降低40%-50%和20%-40%，但对髋骨骨折的相对疗效研究不充分，存在争论。长期使用双膦酸盐的依从性可通过间断性方案得到改善。最近的发展趋势是静脉使用伊班膦酸钠(ibandronate)甚至唑来膦酸钠（zoledronate）（每年输注），唑来膦酸钠试验中显示它能降低椎体和髋骨骨折，且使新近髋骨骨折患者的生存率延长。甲状旁腺功能亢进是骨丢失的原因，间断性应用甲状旁腺素或其片段1-34（teriparatide)能合成骨骼，不过治疗费力和花费高（每日皮下注射18个月），需监测血清钙和尿钙，但结果很好（至少对于椎体骨折）。雷尼酸锶 （ Strontium ranelate）是促骨形成稍弱的药物但也可降低骨吸收，每天使用共3年可降低椎体骨折，从较小程度上来说，也能降低非椎体骨折危险性。最后，denosumab是一种针对RANK配体（特异性阻断破骨细胞形成和活性）的高度亲和力抗体，不久就将清楚其疗效了。

附原文：The most frequent sites of osteoporotic fractures are the vertebrae, the hip, the forearm and the proximal humerus. Drugs that inhibit bone resorption constitute the mainstay for the treatment of postmenopausal osteoporosis. A recent meta-analysis indicates that vitamin D can reduce the risk of hip fractures only if calcium supplements are also administered. The effect of hormone replacement therapy on the risk of non vertebral fractures is less clear than on vertebral fractures. Raloxifene (a SERM) reduces the rate of vertebral fractures and of breast cancer, but it does not protect against hip fracture. Bisphosphonates are the most commonly used compounds to treat postmenopausal osteoporosis. The level of evidence for currently used bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) to reduce vertebral fracture rate is maximal. Results of controlled clinical trials indicate a reduction in the risk of vertebral fractures of 40-50% and of 20-40% for non vertebral fractures, including hip fractures. However, their relative efficacy on hip fractures has been less well studied and remains more controversial. Long-term compliance of bisphosphonate therapy is improved by intermittent schemes. The most recent developpements concern the intravenous administration of ibandronate and even more of zoledronate (yearly infusions). The reduction in the rate of vertebral and hip fractures has been demonstrated in the main zoledronate trial and a prolongation of survival has been shown in the study including patients with a recent hip fracture. Whereas hyperparathyroidism is a cause of bone loss, the intermittent administration of parathyroid hormone or of its 1-34 fragment (teriparatide) exerts anabolic effects on the skeleton. The treatment is demanding and costly (daily sc injections during 18 months), requires some monitoring (serum and urinary calcium) but the results, at least for vertebral fractures, are quite favorable. Strontium ranelate is a less powerful stimulator of bone formation but it also reduces bone resorption. Its daily administration for 3 years reduces the risk of vertebral fractures and, to a lesser extent, of non vertebral fractures. Lastly, denosumab is a high affinity antibody against RANK Ligand that specifically blocks the formation and the activity of osteoclasts. The efficacy of this promising compound will soon be known. （摘自：Body JJ. Update on treatment of postmenopausal osteoporosis. Rev Med Brux, 2008, 29(4):301-9）

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