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骨佩吉特病。治疗进展

Paget's disease of bone. An update on management.

作者信息

Hosking D J

出版信息

Drugs. 1985 Aug;30(2):156-73. doi: 10.2165/00003495-198530020-00004.

Abstract

The essential requirement for effective treatment of Paget's disease of bone is that the characteristic abnormality of bone remodelling is predictably corrected without the occurrence of significant side effects. Although the ideal agent is not currently available, appropriate use of the calcitonins or diphosphonates goes a long way to achieving this goal. Calcitonin (50 to 100 MRC units subcutaneously daily or 3 times weekly) will generally reduce bone turnover by approximately 50% within 6 months. However, very active disease will not be controlled and bone turnover will generally increase once treatment is withdrawn. Calcitonin is without significant side effects, although some patients will develop antibody-mediated resistance to the exogenous calcitonin species. An advantage of calcitonin is that there is radiographic evidence of a return to normal bone remodeling during treatment. Although a number of diphosphonates (now more correctly termed bisphosphonates) are available for experimental use, only the first generation compound, disodium etidronate (EHDP) is commercially available. It too will reduce bone turnover by about 50% within 6 months when given in a dose of 5 mg/kg daily. Unlike calcitonin, it results in a more sustained control of bone turnover while having the additional advantage that it can be given by mouth. Although larger doses are more effective in controlling very active disease, there is a real risk of causing defective bone mineralisation which may result in the development of atraumatic long bone fractures or diffuse bone pains. Combinations of calcitonin and disodium etidronate in conventional dosage seem to result in an additive suppressant effect on bone turnover and may be indicated for more active disease. Advances in treatment are progressing rapidly and it seems likely that in the next few years the introduction of new agents for the control of Paget's disease will more nearly approach the ideal goal of treatment.

摘要

有效治疗骨佩吉特病的基本要求是,可预测地纠正骨重塑的特征性异常,且不出现明显副作用。尽管目前尚无理想药物,但合理使用降钙素或双膦酸盐在很大程度上有助于实现这一目标。降钙素(每日皮下注射50至100 MRC单位或每周3次)通常会在6个月内使骨转换率降低约50%。然而,非常活跃的疾病无法得到控制,且一旦停止治疗,骨转换率通常会升高。降钙素没有明显副作用,尽管一些患者会产生抗体介导的对外源性降钙素种类的耐药性。降钙素的一个优点是,治疗期间有影像学证据表明骨重塑恢复正常。尽管有多种双膦酸盐(现在更准确地称为二膦酸盐)可用于实验,但只有第一代化合物依替膦酸二钠(EHDP)可商业化获取。当每日给予5 mg/kg剂量时,它也会在6个月内使骨转换率降低约50%。与降钙素不同,它能更持续地控制骨转换,还有可口服的额外优点。尽管较大剂量在控制非常活跃的疾病方面更有效,但确实存在导致骨矿化缺陷的风险,这可能会导致无创伤性长骨骨折或弥漫性骨痛。常规剂量的降钙素和依替膦酸二钠联合使用似乎对骨转换有相加的抑制作用,可能适用于更活跃的疾病。治疗进展迅速,未来几年似乎有可能引入控制佩吉特病的新药物,从而更接近治疗的理想目标。

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