ANTIRESORPTIVE THERAPY FOR OSTEOPENIA IN GAUCHER DISEASE

戈谢病是一种常染色体隐性遗传病， 减少葡糖神经酰胺和其他 葡萄糖鞘脂 几乎所有病例都是由于遗传性缺乏 溶酶体葡萄糖脑苷脂酶（GC）缺乏症， 含有未水解葡糖神经酰胺的巨噬细胞蓄积， 肝、脾、骨髓细胞和其他组织中的其他鞘糖脂 单核细胞/巨噬细胞衍生的细胞。 大多数GC缺乏症患者 用注射形式的人GC治疗。 这种疗法导致 肝脏和脾脏中的储存量显著减少，但体征和 与骨骼有关的症状，包括骨痛和骨质减少， 经过多年的改善治疗，或者是顽固的。 然而，大量的临床试验和最近的技术评估 由NIDDK主办的会议认识到， 戈谢病的慢性骨骼衰弱并发症将 需要替代方案和/或预防性干预。 这样做的目的 一个项目是确定大多数成年人的骨质减少是否 高雪氏病可以通过抗吸收治疗来纠正 正在接受酶治疗的戈谢病患者。做 因此，我们将进行一项为期3年的双盲、双臂对照试验， 阿仑膦酸钠，40 mg/天，用于已经接受过 在进入研究之前接受酶治疗至少24个月 study.来自两个主要高雪治疗中心的82名此类患者 将随机分为两组，分别接受酶治疗 (8-60 U/kg/q 2周）与阿仑膦酸钠或安慰剂联合给药24个月。 治疗结果将通过测量骨密度进行监测， 腰椎和骨骼X射线评分的疾病严重程度 入组研究的时间，以及每6个月一次直至研究结束 的研究。 这些研究的成功结果可能会导致新的 控制或逆转戈谢病的治疗方案 骨质减少，并可能导致昂贵的酶疗法的剂量减少。

Gaucher disease is an autosomal recessive disease caused by severely decreased intracellular hydrolysis of glucosylceramides and other glucosphingolipids. Nearly all cases are due to heritable deficiency of lysosomal glucocerebrosidase (GC) deficiency which causes massive accumulation of macrophages containing unhydrolyzed glucosylceramides and other glucosphingolipids in the liver, spleen, bone marrow cells and other monocyte/macrophage-derived cells. Most patients with GC deficiency are treated with injectable forms of human GC. This therapy results in remarkable decreases in storage in liver and spleen, but signs and symptoms relating to bone, including bone pain and osteopenia only occur after years of therapy for improvement or else have been refractory. However, numerous clinical trials and a recent Technology Assessment Conference sponsored by NIDDK have recognized that successful treatment of chronic debilitating skeletal complications of Gaucher disease will require alternatives and/or adjunctive intervention. The purpose of this project is to determine whether the osteopenia that is seen in most adults with Gaucher disease can be corrected by antiresorptive adjunctive therapy in patients with Gaucher disease who are receiving enzyme therapy. To do so, we will perform a 3-year, double-blind, two-arm controlled trial of alendronate, 40 mg/day on adults with Gaucher disease who have been treated at least 24 months with enzyme therapy prior to entry into the study. Eighty-two such patients from two major Gaucher Treatment Centers will be randomized into two groups, which will receive enzyme therapy (8-60 U/kg/q 2 weeks) with alendronate or with placebo for 24 months. Therapeutic outcome will be monitored by measurement of bone density at the lumbar spine and scoring of skeletal x-rays for disease severity at the time of entry into the study, and at 6-month intervals until the end of the study. The successful outcome of these studies may lead to new therapeutic regimens for Gaucher disease that control or reverse osteopenia, and may lead to reduction of dosage in costly enzyme therapy.