Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan.
Division of Molecular Epidemiology, The Jikei University School of Medicine, Tokyo, Japan.
J Bone Miner Metab. 2024 Mar;42(2):264-270. doi: 10.1007/s00774-024-01505-7. Epub 2024 Mar 21.
Denosumab, a fully human anti-RANKL monoclonal antibody, is a widely used osteoporosis treatment that is increasingly being used in patients undergoing dialysis; however, its long-term efficacy and safety in these patients remain unknown.
This observational study comprised individuals aged ≥ 20 years undergoing hemodialysis and receiving denosumab. After denosumab administration, we analyzed the long-term changes in bone mineral density (BMD) and levels of bone turnover markers (BTMs) and calcium.
The study included 45 patients who have been receiving denosumab for a median duration of 3.8 (interquartile range, 2.5-6.7) years. Tartrate-resistant acid phosphatase 5b (TRACP-5b) levels decreased from a median of 595 (434-778) mU/dL at baseline to 200 (141-430) mU/dL after 6 months of denosumab administration (P < 0.001) and remained low thereafter. Similarly, bone-specific alkaline phosphatase (BAP) levels decreased from a median of 18.2 (15.9-25.8) μg/L at baseline to 12.4 (9.9-15.6) μg/L after 6 months (P < 0.001) and remained low thereafter. Meanwhile, BMD, as assessed with dual energy X-ray absorptiometry and measured at the distal 1/3 of the radius, did not decrease (0.465 ± 0.112 g/cm at baseline vs. 0.464 ± 0.112 g/cm after administration; P = 0.616). Regarding hypocalcemia, corrected calcium levels reached were the lowest at 7 days after administration and normalized within 30 days.
The study showed long-term suppression of TRACP-5b and BAP levels and sustaining BMD after denosumab administration over an extended period in patients undergoing hemodialysis.
地舒单抗是一种全人源抗 RANKL 单克隆抗体，广泛用于治疗骨质疏松症，并且越来越多地用于接受透析的患者；然而，其在这些患者中的长期疗效和安全性尚不清楚。
本观察性研究纳入了年龄≥20 岁、正在接受血液透析并接受地舒单抗治疗的患者。在给予地舒单抗后，我们分析了骨密度（BMD）和骨转换标志物（BTMs）及钙的长期变化。
研究共纳入 45 例患者，中位接受地舒单抗治疗时间为 3.8 年（四分位距 2.5-6.7 年）。在给予地舒单抗 6 个月后，抗酒石酸酸性磷酸酶 5b（TRACP-5b）水平从基线时的中位数 595（434-778）mU/dL 降至 200（141-430）mU/dL（P<0.001），此后一直保持低值。同样，骨碱性磷酸酶（BAP）水平从基线时的中位数 18.2（15.9-25.8）μg/L 降至 6 个月时的 12.4（9.9-15.6）μg/L（P<0.001），此后一直保持低值。同时，双能 X 射线吸收法（DXA）测量的桡骨远端 1/3 处 BMD 并未下降（基线时为 0.465±0.112 g/cm，给予地舒单抗后为 0.464±0.112 g/cm；P=0.616）。关于低钙血症，给予地舒单抗后 7 天校正钙水平最低，30 天内恢复正常。
该研究表明，在接受血液透析的患者中，地舒单抗长期使用可抑制 TRACP-5b 和 BAP 水平，并维持 BMD。
