SKELETAL TURNOVER IN OSTEOGENESIS IMPERFECTA--EFFECT OF PAMIDRONATE THERAPY

成骨不全(OI)是一种遗传性骨骼疾病，影响 据估计，美国有2万人的OI是由不同的 影响原-α1或原-α2多肽的突变 1型胶原链。已定义了四种临床OI表型， 从临床病情轻微的I型疾病到II型疾病 致命性疾病、严重的III型疾病和 IV疾病，中度严重。 I型(轻度)OI表型可能包括被认为患有 家族性特发性骨质疏松。I型OI样胶原蛋白异常 甚至在我们的实验室中对轻度成年人的受试者进行了检测 病因不明的骨质疏松症。 虽然许多疗法已经在OI中使用，但没有一种疗法在OI中成功 强化骨骼或降低骨折发生率。双膦酸类药物 已成功用于治疗绝经后骨质疏松症。我们 使用了一种有效的双磷酸盐，帕米膦酸盐(Ciba)， 每三个月静脉注射一次，用于治疗轻度 (第I类)其他。在本研究中，每个受试者都充当自己的对照。学习 参数包括四环素标记骨的组织形态计量学分析 在治疗前和治疗两年后进行活组织检查。数据收集 包括核心实验室分析、饮食历史和CDMAS数据管理。 初步数据分析表明基线骨转换较低。 患有I型OI的受试者。在完成这两项任务的两名受试者中- 一年的疗程，骨密度测量(DEXA)和骨 组织形态计量学结果显示，在一个 主题，在第二个主题中显著。对其他方面的分析 主题悬而未决。帕米膦酸二钠治疗多发性硬化患儿 严重类型的OI对骨量有积极的影响。这个 患有不同类型OI的儿童和成人的反应可能不同。这 考虑到最近可获得的有效数据，数据很重要 口服活性的双磷酸盐，以及对 这些药物对寻求有效治疗的OI人群来说是必要的。

Osteogenesis imperfecta (OI) is a heritable disorder of bone that affects an estimated 20,000 individuals in the U.S. Oi is the result of different mutations affecting either the pro-alpha 1 or pro-alpha 2 polypeptide chains of type 1 collagen. Four clinical OI phenotypes have been defined, ranging from Type I disease which is of mild clinical severity, to Type II disease which is lethal, to Type III disease which is severe, and to Type IV disease which is of moderate severity. The Type I (mild) OI phenotype may include individuals considered to have familial idiopathic osteoporosis. Collagen abnormalities like Type I OI have een determined in our laboratories in subjects with mild adult osteoporosis of undetermined etiology. Although many therapies have been used in OI, none has been successful in strengthening bone or decreasing the fracture rate. Bisphosphanate drugs have been used successfully in treating post-menopausal osteoporosis. We have employed an effective bisphosphanate, Pamidronate (Ciba), administered intraveneously every three months, in the treatment of mild (Type I) OI. In this study, each subject serves as his own control. Study parameters include histomorphometric analysis of tetracycline-labeled bone biopsies obtained before and after two years of treatment. Data collection includes Core Lab analyses, diet history and CDMAS data management. Preliminary data analysis indicates that baseline bone turnover is low in subjects with Type I OI. Of the two subjects who have compeletd the two- year course of treatment, bone densitometry (DEXA) and bone histomorphometry results indicate bone mass has increased slightly in one subject and significantly in the second subject. Analysis of other subjects is pending. Administration of Pamidronate to children with more severe types of OI has demonstrated a positive effect on bone mass. The response of children and adults with different types of OI may vary. This data is important in view of the recent availability of potent bisphosphanates active by oral administration, and the intense interest in these agents on the part of the OI population seeking effective treatment.