Chapurlat Roland D, Delmas Pierre D
University Claude Bernard, Lyon, France.
Nat Clin Pract Endocrinol Metab. 2006 Apr;2(4):211-9; quiz following 238. doi: 10.1038/ncpendmet0121.
Bisphosphonates are potent antiresorptive agents, which have largely been used for the treatment of postmenopausal osteoporosis during the past 10 years. When embedded in bone matrix, bisphosphonates are taken up by osteoclasts engaged in bone resorption, leading--mainly by inhibition of farnesyl diphosphate synthase, a key enzyme of the mevalonate pathway--to osteoclast apoptosis. Bone resorption decreases, with consequent improvement in the mechanical properties of bone and a reduced risk of fracture. Alendronate and risedronate are oral nitrogen-containing bisphosphonates. Several randomized, placebo-controlled trials have shown the ability of these bisphosphonates to halve the risk of vertebral fracture when taken daily for 3 years. Nonvertebral fracture risk, including that at the hip, was also significantly decreased. Weekly regimens have simplified the administration of bisphosphonates and, probably, improved adherence to treatment. A significant reduction in the risk of vertebral fracture has also been demonstrated with an intermittent regimen of ibandronate, which is a new, potent, nitrogen-containing bisphosphonate. Ibandronate was recently marketed for use in an oral, once-monthly dose of 150 mg, with the goal of improving compliance. Bisphosphonates are usually well tolerated in the long term. Intravenous administration of bisphosphonates in women with osteoporosis, which is currently under investigation, might be an interesting future option for women who cannot tolerate oral regimens, and for enhancing compliance.
双膦酸盐是强效抗骨吸收药物，在过去10年中主要用于治疗绝经后骨质疏松症。当双膦酸盐嵌入骨基质中时，参与骨吸收的破骨细胞会摄取它们，主要通过抑制甲羟戊酸途径的关键酶法尼基二磷酸合酶，导致破骨细胞凋亡。骨吸收减少，从而改善骨的力学性能并降低骨折风险。阿仑膦酸钠和利塞膦酸钠是口服含氮双膦酸盐。多项随机、安慰剂对照试验表明，这些双膦酸盐连续3年每日服用时，可使椎体骨折风险减半。包括髋部骨折在内的非椎体骨折风险也显著降低。每周给药方案简化了双膦酸盐的给药方式，可能还提高了治疗依从性。一种新型强效含氮双膦酸盐伊班膦酸钠的间歇给药方案也已证明可显著降低椎体骨折风险。伊班膦酸钠最近上市，口服剂量为每月1次，每次150mg，目的是提高依从性。双膦酸盐通常长期耐受性良好。目前正在研究骨质疏松症女性静脉注射双膦酸盐，这对于无法耐受口服给药方案的女性以及提高依从性而言，可能是一个有趣的未来选择。
