Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
Nephrology Center, Makita General Hospital, Tokyo, Japan.
J Bone Miner Res. 2019 Jun;34(6):1014-1024. doi: 10.1002/jbmr.3676. Epub 2019 Mar 4.
Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate are effective and safe treatments in hemodialysis patients is not known. Thus, we conducted a prospective, three-center study of 48 hemodialysis patients who were diagnosed as having osteoporosis and had not received anti-osteoporotic agents previously. Participants were randomized to either denosumab or intravenous alendronate, and all subjects received elemental calcium and calcitriol during the initial 2 weeks. The primary endpoint was the percent change in lumbar spine bone mineral density (LSBMD) at 12 months of treatment. The secondary endpoints included the following: change in BMD at other sites; change of serum bone turnover markers (BTM), coronary artery calcium score (CACS), ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), flow mediated dilation (FMD), and intima-media thickness at the carotid artery (CA-IMT); change from day 0 to day 14 in serum levels of Ca and P; time course of serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (i-PTH); new fractures; and adverse events. Initial supplementation with elemental calcium and calcitriol markedly ameliorated the decrease of serum corrected calcium (cCa) levels induced by denosumab during the first 2 weeks, whereas serum cCa levels in the alendronate group were increased. Denosumab and alendronate markedly decreased serum levels of BTM and increased LSBMD at 12 months compared with baseline. However, no significant differences were found in the changes in LSBMD between the two groups. The serum cCa, P, and i-PTH levels in the two groups were maintained within the appropriate range. In contrast to the anti-osteoporotic effects, no significant differences after 12 months of treatment were found in the CACS, CA-IMT, ABI, baPWV, and FMD compared with pretreatment in both groups. Denosumab and alendronate treatment improved LSBMD, reduced BTM, and appeared to be safe in hemodialysis patients with osteoporosis. © 2019 American Society for Bone and Mineral Research.
矿物质和骨骼疾病，包括骨质疏松症，在透析患者中很常见，并导致发病率和死亡率增加。然而，地舒单抗和阿仑膦酸钠是否对血液透析患者有效和安全尚不清楚。因此，我们进行了一项前瞻性、三中心研究，纳入了 48 名先前未接受过抗骨质疏松药物治疗的被诊断为骨质疏松症的血液透析患者。参与者被随机分配至地舒单抗组或静脉用阿仑膦酸钠组，所有受试者在最初的 2 周内均接受元素钙和骨化三醇治疗。主要终点是治疗 12 个月时腰椎骨密度（LSBMD）的百分比变化。次要终点包括以下内容：其他部位骨密度的变化；血清骨转换标志物（BTM）、冠状动脉钙评分（CACS）、踝臂血压指数（ABI）、肱踝脉搏波速度（baPWV）、血流介导的舒张功能（FMD）和颈动脉内-中膜厚度（CA-IMT）的变化；从第 0 天到第 14 天血清 Ca 和 P 水平的变化；血清 Ca、P 和全段甲状旁腺激素（i-PTH）的时间过程；新发骨折；以及不良事件。最初补充元素钙和骨化三醇可显著改善地舒单抗在最初 2 周内引起的血清校正钙（cCa）水平下降，而阿仑膦酸钠组的血清 cCa 水平升高。与基线相比，地舒单抗和阿仑膦酸钠在 12 个月时均可显著降低血清 BTM 水平并增加 LSBMD。然而，两组之间 LSBMD 的变化无显著差异。两组的血清 cCa、P 和 i-PTH 水平均维持在适当范围内。与抗骨质疏松作用不同，与治疗前相比，两组在治疗 12 个月后，CACS、CA-IMT、ABI、baPWV 和 FMD 均无显著差异。地舒单抗和阿仑膦酸钠治疗可改善 LSBMD、降低 BTM，且似乎对血液透析合并骨质疏松症患者安全。
