Stover S L, Hahn H R, Miller J M
Paraplegia. 1976 Aug;14(2):146-56. doi: 10.1038/sc.1976.25.
Heterotopic ossification is a frequent complication following spinal cord injury with 16 per cent to 53 per cent of patients developing varying degrees of pathologic ossification. The diphosphonates are known to block the transformation of amorphous calcium phosphate into crystalline hydroxyapatite. Therefore, one of the diphosphonates, disodium etidronate (generic name of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was selected fro clinical trials to study the effectiveness of EHDP in preventing heterotopic ossification following spinal cord injury. In a double-blind, clinical study of 149 spinal cord injury patients, disodium etidronate has proven its effectiveness in the prevention of heterotopic ossification. The extent of heterotopic ossification development as measured by the total heterotopic ossification X-ray grade was significantly less in EHDP-treated patients compared to placebo-treated patients (P less than 0-05). For maximal effectiveness, EHDP treatment must be started before the onset of the pathological process initiating the development of heterotopicossification. Further studies are necessary to determine the optimal time to institute EHDP treatment, length of treatment, and minimal effective dose. EHDP is the first hterapeutic agent known to alter the formation of heterotopic ossification after spinal injury and may prove useful in other conditions where heterotopic ossification prevention is clinically indicated.
异位骨化是脊髓损伤后常见的并发症,16%至53%的患者会出现不同程度的病理性骨化。已知双膦酸盐可阻止无定形磷酸钙转化为结晶性羟基磷灰石。因此,选择其中一种双膦酸盐依替膦酸二钠(乙烷-1-羟基-1,1-二膦酸二钠(EHDP)的通用名)进行临床试验,以研究EHDP预防脊髓损伤后异位骨化的有效性。在一项对149例脊髓损伤患者的双盲临床研究中,依替膦酸二钠已证明其在预防异位骨化方面的有效性。与安慰剂治疗的患者相比,经EHDP治疗的患者通过异位骨化X线总分级测量的异位骨化发展程度明显更低(P小于0.05)。为达到最大疗效,EHDP治疗必须在引发异位骨化发展的病理过程开始之前启动。需要进一步研究以确定开始EHDP治疗的最佳时间、治疗时长和最小有效剂量。EHDP是已知的第一种能改变脊髓损伤后异位骨化形成的治疗药物,可能在临床上有预防异位骨化指征的其他情况中有用。