ANTIRESORPTIVE THERAPY FOR OSTEOPENIA IN GAUCHER DISEASE

高谢病是一种常染色体隐性遗传病，由严重 减少葡萄糖神经酰胺和其他物质的细胞内水解率 葡萄糖脂。几乎所有的病例都是由于遗传缺陷引起的 溶酶体葡萄糖脑苷酶(GC)缺乏症 含有未水解性葡萄糖神经酰胺的巨噬细胞的蓄积和 肝、脾、骨髓细胞等中的其他鞘糖脂 单核/巨噬细胞来源的细胞。大多数GC缺乏症患者 使用可注射形式的人GC进行治疗。这种疗法的结果是 肝和脾的储存量显著减少，但有迹象表明 只会出现与骨骼有关的症状，包括骨痛和骨量减少 经过多年的治疗，要么好转，要么就一直难治。 然而，大量的临床试验和最近的技术评估 由NIDDK主办的会议已经认可了成功的治疗 高谢病的慢性骨骼并发症将 需要替代方案和/或辅助干预。这样做的目的是 项目是确定大多数成年人出现的骨量减少症 高谢病可以通过抗吸收辅助治疗来纠正 在接受酶治疗的高谢病患者中。去做 因此，我们将进行一项为期3年的双盲双臂对照试验 阿伦磷酸钠，40毫克/天，用于患有高谢病的成人 在进入前至少24个月接受酶疗法治疗 学习。来自两个主要高谢尔治疗中心的82名这样的患者 将被随机分成两组，接受酶疗法 (8-60U/kg/q，2周)，用阿仑磷酸钠或安慰剂治疗24个月。 治疗结果将通过测量骨密度来监测。 腰椎和骨骼X光评分对疾病严重程度的影响 进入研究的时间，每隔6个月直到研究结束 这项研究的结果。这些研究的成功结果可能会带来新的 控制或逆转高谢病的治疗方案 骨量减少，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.