Denosumab-Mediated Increase in Hand Bone Mineral Density Associated With Decreased Progression of Bone Erosion in Rheumatoid Arthritis Patients
Denosumab-Mediated Increase in Hand Bone Mineral Density Associated With Decreased Progression of Bone Erosion in Rheumatoid Arthritis Patients
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DOI：
10.1002/acr.20004
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发表时间：
2010-04-01
影响因子：
4.7
通讯作者：
Newmark, R.
中科院分区：
文献类型：
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作者：
Deodhar, A.;Dore, R. K.;Newmark, R.
Objective.关节周围骨质疏松是类风湿关节炎（RA）骨损害的最早影像学征象之一。Denosumab是一种研究性全人源单克隆抗体，与RANKL结合，在RA患者的临床研究中抑制骨侵蚀和全身性骨丢失。在这项手部骨矿物质密度（BMD）子研究中，我们研究了地舒单抗对手部BMD的影响及其与手部糜烂评分的相关性。接受甲氨蝶呤治疗糜烂性RA的患者在0和6个月时以1：1：1的比例随机接受皮下安慰剂、地舒单抗60 mg或地舒单抗180 mg。测量包括双手（0、1、6和12个月）的BMD（双能X线骨密度仪[DXA]）、手/腕的磁共振图像（0和6个月）以及手/腕和脚的X线照片（0、6和12个月）。共有56例患者（安慰剂组13例、地舒单抗60 mg组21例和地舒单抗180 mg组22例）。6个月和12个月时手部BMD的平均变化分别为：地舒单抗60 mg组分别为+0.8%和+1.0%;地舒单抗180 mg组分别为+2.0%和+2.5%;安慰剂组分别为-1.2%和-2.0%。地舒单抗组的糜烂评分保持接近基线，安慰剂组较基线升高。手部骨密度与糜烂评分呈负相关。在RA患者中，地舒单抗可提供抗侵蚀保护，不仅可预防骨丢失，还可增加DXA测量的手部BMD。
Objective. Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores.Methods. Patients receiving methotrexate for erosive RA were randomized in a 1: 1: 1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months).Results. There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores.Conclusion. In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.