Changes in serum receptor activator of nuclear factor-κB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34)
Changes in serum receptor activator of nuclear factor-κB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34)
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DOI：
10.1210/jc.2003-032066
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发表时间：
2004-07-01
影响因子：
5.8
通讯作者：
Lane, NE
中科院分区：
文献类型：
--
作者：
Buxton, EC;Yao, W;Lane, NE
间歇注射人（h）PTH（1-34）后骨转换生化标志物的变化表明，骨形成最初优于骨吸收。还已知hPTH（1-34）通过调节成骨细胞衍生的细胞因子，如核因子-κ B配体（RANKL）、骨保护素（OPG）、IL-6和IL-6可溶性受体（IL-6sR）的受体活化剂，影响破骨细胞的成熟和活性。在本实验中，我们研究了接受hPTH（1-34）治疗的糖皮质激素诱导的骨质疏松症患者血清可溶性RANKL（sRANKL）、OPG、IL-6和IL-6sR水平的变化。51名绝经后糖皮质激素性骨质疏松症妇女随机分为两组，一组接受400 U hPTH（1-34）（类似于40 μ g）每日一次治疗，另一组接受标准激素替代治疗，或单独接受激素替代治疗，为期12个月。在基线、1个月和此后每3个月测量sRANKL、OPG、IL-6和IL-6sR的血清水平，共24个月。hPTH（1-34）在1个月内引起sRANKL的快速和显著增加，并且在整个治疗期间水平保持升高。IL-6和IL-6sR在1个月内显著升高，但更快地恢复到基线水平。相比之下，OPG在hPTH治疗后6个月开始受到轻度抑制。这些数据支持hPTH（1-34）最初刺激成骨细胞成熟和功能的假设，这反过来又导致破骨细胞活化和骨形成和吸收的逐渐再平衡。
Changes in biochemical markers of bone turnover following intermittent injections of human (h) PTH (1-34) suggest that bone formation is initially favored over bone resorption. hPTH (1-34) is also known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines, such as receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), IL-6, and IL-6 soluble receptor (IL-6sR). In this experiment, we investigated the changes in serum levels of soluble RANKL (sRANKL), OPG, IL-6, and IL-6sR in patients with glucocorticoid-induced osteoporosis treated with hPTH (1-34). Fifty-one postmenopausal women with glucocorticoid-induced osteoporosis were randomized to receive 12 months of 400 U hPTH (1-34) (similar to40 mug) daily and standard hormone replacement therapy, or hormone replacement therapy alone. Serum levels of sRANKL, OPG, IL-6, and IL-6sR were measured at baseline, 1 month, and every 3 months thereafter for a total of 24 months. hPTH (1-34) caused a rapid and significant increase in sRANKL within 1 month, and the levels remained elevated throughout the duration of therapy. IL-6 and IL-6sR increased significantly within 1 month, but returned to baseline levels more rapidly. In contrast, OPG was mildly suppressed beginning 6 months after hPTH therapy. These data support the hypothesis that hPTH (1-34) initially stimulates osteoblast maturation and function, which in turn leads to osteoclast activation and a gradual rebalancing of bone formation and resorption.