Johansen A, Stone M, Rawlinson F
Academic Department of Geriatrics, University of Wales College of Medicine, Cardiff.
Drugs Aging. 1996 Feb;8(2):113-26. doi: 10.2165/00002512-199608020-00005.
Recognition of the way in which naturally occurring pyrophosphate affects bone metabolism has stimulated the development of a whole series of related compounds, the bisphosphonates. Although the precise mechanism of action of these compounds remains incompletely understood, they have been proven profoundly effective in clinical practice and already constitute a major advance in the therapy of conditions characterised by excessive bone resorption. Serious adverse effects are rare; however, mineralisation problems are a concern, particularly with etidronate. The reduction in bone turnover during prolonged treatment for osteoporosis is also a concern but as yet of uncertain clinical importance. The wide variation in potency of different bisphosphonates in inhibiting the resorption, mineralisation and turnover of bone will increasingly determine which agents are used in various clinical situations. Bisphosphonates are the treatment of choice in Paget's disease and hypercalcaemia of malignancy. They also appear to have potential to alter the course of metastatic bony disease, although the magnitude and clinical importance of any such effect remains unclear. Bisphosphonates show promise in the prevention and treatment of osteoporosis and increase bone mass in postmenopausal and steroid-induced osteoporosis. The effects of these drugs in other situations are less clear and the effects on fracture rates are not yet fully characterised. Optimal regimens have yet to be established but the long half-lives of these agents makes intermittent treatment a rational and convenient approach.
对天然存在的焦磷酸盐影响骨代谢方式的认识，推动了一系列相关化合物——双膦酸盐的研发。尽管这些化合物的确切作用机制仍未完全明了，但它们在临床实践中已被证明具有显著疗效，并且在治疗以骨吸收过多为特征的病症方面已然取得了重大进展。严重的不良反应较为罕见；然而，矿化问题令人担忧，尤其是依替膦酸。在骨质疏松症的长期治疗过程中，骨转换率降低也是一个问题，但目前其临床重要性尚不确定。不同双膦酸盐在抑制骨吸收、矿化和转换方面的效力差异巨大，这将越来越多地决定在各种临床情况下使用何种药物。双膦酸盐是佩吉特病和恶性肿瘤高钙血症的首选治疗药物。它们似乎也有改变转移性骨病病程的潜力，尽管这种效应的程度和临床重要性仍不明确。双膦酸盐在预防和治疗骨质疏松症方面显示出前景，并能增加绝经后和类固醇诱导的骨质疏松症患者的骨量。这些药物在其他情况下的效果尚不清楚，对骨折率的影响也尚未完全明确。最佳治疗方案尚未确立，但这些药物的长半衰期使得间歇性治疗成为一种合理且方便的方法。
