Chen Chien-Liang, Chen Nai-Ching, Hsu Chih-Yang, Chou Kang-Ju, Lee Po-Tsang, Fang Hua-Chang, Renn Jenn-Huei
Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., P.-T.L., H.-C.F.) and Department of Orthopedics (J.-H.R.), Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; Department of Medicine (C.-L.C., C.-Y.H., K.-J.C., P.-T.L., H.-C.F.), National Yang-Ming University School of Medicine, Taipei 112, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 333, Taiwan; and College of Pharmacy and Health Care (J.-H.R.), Tajen University, Pintong County 907, Taiwan.
J Clin Endocrinol Metab. 2014 Jul;99(7):2426-32. doi: 10.1210/jc.2014-1154. Epub 2014 Mar 26.
Denosumab is widely used for bone diseases with increased bone resorption. Its effectiveness in patients with severe secondary hyperparathyroidism on dialysis is unclear.
This study aimed to evaluate the efficacy and safety of denosumab in patients with severe secondary hyperparathyroidism who are on dialysis.
This 6-month prospective, open-labeled study evaluated 12 patients (five women, seven men; mean age 53.5 ± 3.8 y). All had intact PTH (iPTH; > 1000 pg/mL), low bone mass (T-score < -1.0 SD), and bone pain and were poor surgical candidates. Serum calcium, phosphorus, alkaline phosphatase (AP), and iPTH levels were assessed at baseline and every month thereafter. Vertebral spine x-rays and bone mineral densities (BMDs) (lumbar spine and femoral neck) were assessed at the start and end of the study. All patients received denosumab (60 mg), calcitriol, phosphate binders, and dialysate calcium that were adjusted according to the biochemistry data.
The BMD increased in both the femoral neck (mean increase 23.7% ± 4.0%) and lumbar spine (17.1% ± 2.6%) after 6 months. In the first month, most patients had increased iPTH levels, which dramatically decreased from 1702.1 ± 181.9 to 518.8 ± 126.8 pg/mL by the end of the study after increasing the calcitriol dose. All patients had significant decreases in AP, calcium × phosphorus, and bone pain. Changes in femoral neck BMD correlated only with AP and iPTH levels.
Denosumab is effective in restoring bone mass and reducing bone pain in patients on dialysis with secondary hyperparathyroidism. It also allows for a more aggressive use of calcitriol to control hyperparathyroidism.
地诺单抗广泛用于骨吸收增加的骨病。其在重度继发性甲状旁腺功能亢进透析患者中的有效性尚不清楚。
本研究旨在评估地诺单抗在重度继发性甲状旁腺功能亢进透析患者中的疗效和安全性。
这项为期6个月的前瞻性、开放标签研究评估了12例患者（5名女性，7名男性；平均年龄53.5±3.8岁）。所有患者的全段甲状旁腺激素（iPTH；>1000 pg/mL）、骨量低（T值<-1.0 SD）且有骨痛，均不适合手术。在基线时及之后每月评估血清钙、磷、碱性磷酸酶（AP）和iPTH水平。在研究开始和结束时评估脊柱X光片和骨密度（腰椎和股骨颈）。所有患者均接受地诺单抗（60 mg）、骨化三醇、磷结合剂和根据生化数据调整的透析液钙。
6个月后，股骨颈（平均增加23.7%±4.0%）和腰椎（17.1%±2.6%）的骨密度均增加。在第一个月，大多数患者的iPTH水平升高，在增加骨化三醇剂量后，到研究结束时iPTH水平从1702.1±181.9 pg/mL大幅降至518.8±126.8 pg/mL。所有患者的AP、钙×磷和骨痛均显著降低。股骨颈骨密度的变化仅与AP和iPTH水平相关。
地诺单抗在恢复继发性甲状旁腺功能亢进透析患者的骨量和减轻骨痛方面有效。它还允许更积极地使用骨化三醇来控制甲状旁腺功能亢进。
