Doggrell Sheila A
Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
Drugs Today (Barc). 2003 Aug;39(8):633-57. doi: 10.1358/dot.2003.39.8.799409.
Although neither calcium nor vitamin D has been shown to prevent osteoporosis in postmenopausal women alone, the combination does. Both calcium and vitamin D are commonly used in the treatment of osteoporosis. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who have already had fractures and some evidence that estrogen does as well. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. The bisphosphonate alendronate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women, and in osteoporotic men. Risedronate is more potent and has fewer upper gastrointestinal side effects than alendronate, and reduces the incidence of fractures in osteoporotic women. Intermittent use of the potent bisphosphonate zoledronate also increases bone mineral density and may become an alternative in the prevention and treatment of osteoporosis. All of the agents discussed above prevent bone resorption, whereas teriparatide increases bone formation and is effective in the treatment of osteoporotic women and men. In the treatment of secondary osteoporosis associated with the use of glucocorticoids to treat inflammation or prevent rejection after transplantation, the bisphosphonates are effective. The agents that have undergone some clinical trialing as new or alternative drugs for the treatment of osteoporosis include tibolone, new SERMs, androgens, growth hormone, insulin-like growth factor-1 and stontium ranelate. The targets/drugs that are being developed to inhibit bone resorption include the OPG/ RANKL/RANK system, cathepsin K inhibitors, vitronectin receptor antagonists, estren, the interleukin-6 and gp130 system, cytokines and growth factors. New drugs/targets to promote bone formation include the commonly used lipid-lowering statins and the calcilytic release of PTH.
尽管单独使用钙或维生素D均未被证明可预防绝经后妇女的骨质疏松症，但两者联合使用则有此效果。钙和维生素D都常用于骨质疏松症的治疗。雌激素和雷洛昔芬均可预防绝经后妇女的骨质流失，并且雌激素可能还会降低首次骨折的风险。有充分证据表明，雷洛昔芬可预防已发生骨折的绝经后妇女再次骨折，也有一些证据表明雌激素也有此作用。降钙素可增加绝经早期妇女以及患有特发性骨质疏松症的男性的骨矿物质密度，还可降低骨质疏松症女性发生新骨折的风险。双膦酸盐阿仑膦酸钠可预防健康和骨质疏松的绝经后妇女以及骨质疏松男性的骨质流失并减少骨折。利塞膦酸钠比阿仑膦酸钠效力更强，上消化道副作用更少，可降低骨质疏松症女性的骨折发生率。间歇性使用强效双膦酸盐唑来膦酸也可增加骨矿物质密度，可能成为预防和治疗骨质疏松症的一种选择。上述所有药物均能抑制骨吸收，而特立帕肽可促进骨形成，对治疗骨质疏松症的女性和男性有效。在治疗与使用糖皮质激素治疗炎症或预防移植后排斥反应相关的继发性骨质疏松症时，双膦酸盐有效。已进行一些临床试验作为治疗骨质疏松症的新药或替代药物的制剂包括替勃龙、新型选择性雌激素受体调节剂、雄激素、生长激素、胰岛素样生长因子-1和雷奈酸锶。正在研发的抑制骨吸收的靶点/药物包括骨保护素/核因子κB受体活化因子配体/核因子κB受体活化因子系统、组织蛋白酶K抑制剂、玻连蛋白受体拮抗剂、雌激素、白细胞介素-6和糖蛋白130系统、细胞因子和生长因子。促进骨形成的新药/靶点包括常用的降脂他汀类药物和甲状旁腺激素的钙敏释放。
