Khairallah Pascale, Cortez Natalia E, McMahon Donald J, Sammons Stephen, Agarwal Sanchita, Crew R John, Cohen David J, Dube Geoffrey K, Mohan Sumit, Chang Jae-Hyung, Morris Heather K, Fernandez Hilda E, Aponte Maria Alejandra, Adebayo Aderemi O, Aghi Andrea, Zaninotto Martina, Plebani Mario, Tripepi Giovanni, Gallieni Maurizio, Cosma Chiara, Fusaro Maria, Nickolas Thomas L
Department of Medicine, University of California, San Francisco, CA, 94110, United States.
Department of Clinical and Biological Sciences, University of Turin, Turin, 10124, Italy.
J Bone Miner Res. 2025 May 24;40(5):603-616. doi: 10.1093/jbmr/zjaf044.
A significant number of kidney transplant recipients have low BMD. We hypothesized that calcitriol administration over the first year posttransplantation would protect the cortical skeleton in recipients managed without corticosteroids by suppressing PTH and bone remodeling. In this double-blind, placebo-controlled trial, 67 participants aged ≥18 yr on corticosteroid-sparing immunosuppressive regimen were randomized to daily calcitriol 0.5 μg or placebo for 12 mo after transplantation. The primary endpoint was the percent change in cortical density at the radius and tibia from pre- to postcalcitriol treatment compared to placebo as measured by HR-pQCT. Areal BMD was measured by DXA. Cortical and trabecular volumetric BMD and microarchitecture and total estimated bone strength were measured by HR-pQCT. Blood samples for bone metabolic markers were obtained at baseline, 1- and 12 mo. All primary analyses were intent to treat. Safety was assessed for hypercalcemia and progression of vascular calcifications. Thirty-two participants received calcitriol and 29 received placebo; 27 and 27 participants completed the study, respectively. Most participants were male and Caucasian. Baseline Z-scores at all sites were within 0.5 SD of the general population. At 12 mo posttransplantation, there were no between-group differences in areal BMD, volumetric BMD, microarchitecture or bone strength, or serum levels of bone markers. Participants with versus without bone loss had a blunted anabolic response over 12 mo measured by serum bone markers. Hypercalcemia was higher in the calcitriol group compared to placebo (p < .001). No changes in arterial calcification scores were observed. In this randomized placebo-controlled study of calcitriol administration in kidney transplant recipients on corticosteroid-sparing immunosuppression, calcitriol did not improve bone quality and strength but was associated with higher rates of hypercalcemia.
相当数量的肾移植受者存在低骨密度。我们假设，在移植后的第一年给予骨化三醇，通过抑制甲状旁腺激素（PTH）和骨重塑，可保护未使用皮质类固醇治疗的受者的皮质骨。在这项双盲、安慰剂对照试验中，67名年龄≥18岁且采用皮质类固醇节约免疫抑制方案的参与者在移植后被随机分配，每天服用0.5μg骨化三醇或安慰剂，为期12个月。主要终点是通过高分辨率外周定量计算机断层扫描（HR-pQCT）测量，与安慰剂相比，骨化三醇治疗前后桡骨和胫骨皮质密度的变化百分比。通过双能X线吸收法（DXA）测量面积骨密度。通过HR-pQCT测量皮质和小梁体积骨密度、微结构以及总估计骨强度。在基线、1个月和12个月时采集血液样本检测骨代谢标志物。所有主要分析均采用意向性分析。评估高钙血症和血管钙化进展的安全性。32名参与者接受骨化三醇治疗，29名接受安慰剂治疗；分别有27名和27名参与者完成了研究。大多数参与者为男性和白种人。所有部位的基线Z评分均在一般人群的0.5个标准差范围内。移植后12个月时，两组在面积骨密度、体积骨密度、微结构或骨强度以及骨标志物血清水平方面均无差异。通过血清骨标志物测量，有骨丢失和无骨丢失的参与者在12个月内的合成代谢反应均减弱。与安慰剂相比，骨化三醇组的高钙血症发生率更高（p<0.001）。未观察到动脉钙化评分的变化。在这项对采用皮质类固醇节约免疫抑制的肾移植受者给予骨化三醇的随机安慰剂对照研究中，骨化三醇并未改善骨质量和强度，但与较高的高钙血症发生率相关。
