The effect of a single dose of osteoprotegerin in postmenopausal women
The effect of a single dose of osteoprotegerin in postmenopausal women
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DOI：
10.1359/jbmr.2001.16.2.348
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发表时间：
2001-02-01
影响因子：
6.2
通讯作者：
Dunstan, CR
中科院分区：
文献类型：
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作者：
Bekker, PJ;Holloway, D;Dunstan, CR
骨保护素（OPG）是肿瘤坏死因子（TNF）受体家族成员，是骨吸收的重要调节因子。它是破骨细胞终末分化和活化的重要抑制剂。在绝经后女性中进行了这项随机、双盲、安慰剂对照、序贯剂量递增研究，以确定OPG单次皮下（sc）给药对骨吸收的影响，骨吸收由生化标志物、尿N-端肽（NTS）和脱氧吡啶啉（DPD）（稳定的胶原降解产物）指示。OPG给药后12 h内NTS水平下降。在最高给药剂量（3.0 mg/kg）下，给药后4天观察到NTS平均百分比降低约80%，给药后6周观察到NTX平均降低14%。骨特异性碱性磷酸酶（BSAP）（骨形成的标志物）的水平在给药后约3周内未发生变化。此后，在3.0 mg/kg剂量组中观察到适度降低，6周时达到约30%。NTS较基线快速下降和BSAP延迟下降表明OPG主要作用于破骨细胞以减少骨吸收，OPG注射剂耐受性良好。这项研究首次表明，单次皮下注射OPC可有效地持续快速和深刻地降低骨转换，因此OPG可有效治疗以骨吸收增加为特征的骨疾病，如骨质疏松症。
Osteoprotegerin (OPG), a tumor necrosis factor (TNF) receptor family member, is a critical regulator of bone resorption. It is an important inhibitor of the terminal differentiation and activation of osteoclasts. This randomized, double-blind, placebo-controlled, sequential dose escalation study was conducted in postmenopausal women to determine the effect of a single subcutaneous (sc) dose of OPG on bone resorption as indicated by the biochemical markers, urinary N-telopeptide (NTS) and deoxypyridinoline (DPD), which are stable collagen degradation products. NTS levels decreased within 12 h after OPG administration. At the highest dose administered (3.0 mg/kg), a mean percent decrease in NTS of approximately 80% was observed 4 days after dosing, Six weeks after dosing a mean decrease of 14% in NTX was observed. The levels of bone-specific alkaline phosphatase (BSAP), a marker of bone formation, did not change for approximately 3 weeks after dosing. Thereafter, a modest decrease, reaching approximately 30% at 6 weeks, was observed in the 3.0-mg/kg dose group. The rapid decrease from baseline in NTS and delayed decrease in BSAP indicated that OPG acted primarily on osteoclasts to decrease bone resorption, OPG injections are well tolerated. This study, for the first time, indicates that a single sc injection of OPC is effective in rapidly and profoundly reducing bone turnover for a sustained period and that OPG therefore may be effective in treatment of bone diseases characterized by increased bone resorption such as osteoporosis.