LONG-TERM TREATMENT OF OSTEOPETROSIS WITH RECOMBINANT HUMAN INTERFERON-GAMMA
LONG-TERM TREATMENT OF OSTEOPETROSIS WITH RECOMBINANT HUMAN INTERFERON-GAMMA
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DOI：
10.1056/nejm199506153322402
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发表时间：
1995-06-15
影响因子：
158.5
通讯作者：
RIES, WL
中科院分区：
文献类型：
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作者：
KEY, LL;RODRIGUIZ, RM;RIES, WL
背景。先天性石骨症是一种罕见的骨硬化性骨病，其特征是破骨细胞功能缺陷和白细胞产生的超氧化物减少。这种疾病在生命的头十年通常是致命的。对 8 名骨硬化症患者进行的为期 6 个月的重组人干扰素 γ-1b 治疗试验提供了有益的证据，促使这项研究进行更长期的治疗。方法。我们对 14 名严重骨石症患者进行了研究，每周 3 次皮下注射重组人干扰素 γ-1b（每剂每公斤体重 1.5 微克），持续至少 6 个月； 11名患者接受了18个月的治疗。我们通过评估患者的临床状态、测量血细胞计数和骨转换生化标志物以及进行骨髓成像和骨活检来评估治疗效果。结果。治疗 6 个月后，所有 14 名患者的骨小梁面积均减少（通过骨活检标本的组织形态计量学分析确定），骨髓空间增加（通过骨髓成像确定），并且治疗 18 个月的 11 名患者的改善持续存在。平均 (+/-SD) 血红蛋白浓度从 7.5+/-2.9 增加至 10.5+/-0.3 g/分升 (P=0.05)，并且粒细胞-巨噬细胞集落产生的超氧化物增加 (P
Background. Congenital osteopetrosis is a rare osteosclerotic bone disease characterized by both a defect in osteoclastic function and reduced generation of superoxide by leukocytes. The disease is frequently fatal during the first decade of life. A six-month trial of therapy with recombinant human interferon gamma-lb in eight patients with osteopetrosis provided evidence of benefit, prompting this study of more prolonged therapy.Methods. We studied 14 patients with severe osteopetrosis treated with subcutaneous injections of recombinant human interferon gamma-1b (1.5 mu g per kilogram of body weight per dose) three times per week for at least 6 months; 11 patients were treated for 18 months. We assessed the effect of therapy by evaluating the patients' clinical status, measuring blood counts and biochemical markers of bone turnover, and performing bone marrow imaging and bone biopsies.Results. After 6 months of therapy, all 14 patients had decreases in trabecular-bone area (determined by histomorphometric analysis of bone-biopsy specimens) and increases in bone marrow space (determined by marrow imaging), and the improvement was sustained in the 11 patients treated for 18 months. The mean (+/-SD) hemoglobin concentration increased from 7.5+/-2.9 to 10.5+/-0.3 g per deciliter (P=0.05), and superoxide generation by granulocyte-macrophage colonies increased (P