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Randomized Controlled Trial
. 2025 May 24;40(5):603-616.
doi: 10.1093/jbmr/zjaf044.

Calcitriol supplementation after kidney transplantation: results of a double-blinded, randomized, placebo-controlled trial

Pascale Khairallah  1 , Natalia E Cortez  2 , Donald J McMahon  3 , Stephen Sammons  4 , Sanchita Agarwal  3 , R John Crew  3 , David J Cohen  3 , Geoffrey K Dube  3 , Sumit Mohan  3 , Jae-Hyung Chang  3 , Heather K Morris  3 , Hilda E Fernandez  3 , Maria Alejandra Aponte  3 , Aderemi O Adebayo  5 , Andrea Aghi  6 , Martina Zaninotto  7 , Mario Plebani  8 , Giovanni Tripepi  9 , Maurizio Gallieni  10 , Chiara Cosma  8 , Maria Fusaro  8   9 , Thomas L Nickolas  11
Affiliations
Randomized Controlled Trial

Calcitriol supplementation after kidney transplantation: results of a double-blinded, randomized, placebo-controlled trial

Pascale Khairallah et al. J Bone Miner Res. .

Abstract

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.

Keywords: bone density; calcitriol; osteoporosis; transplant; trial.

Plain language summary

Kidney transplant recipients face a heightened risk of bone loss due to medication effects and metabolic changes. This study assessed whether oral calcitriol (active vitamin D) helps prevent bone loss in recipients managed with steroid-free immunosuppression. Sixty-seven patients received either calcitriol or a placebo for 12 mo. No significant differences in bone density, quality, or strength were found. The changes in biochemical markers were similar in both groups. However, hypercalcemia occurred at a higher rate with calcitriol as compared to placebo. We concluded that calcitriol did not prevent bone loss but increased hypercalcemia risk. Therefore, routine use may not be necessary if vitamin D levels are adequate.

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Conflict of interest statement

P.K., N.E.C., S.A., D.J.M., S.S., S.A., M.A.A., A.O.A., A.A., M.P., M.Z., C.C., R.J.C., D.J.C., G.K.D., S.M., J.H.C., H.K.M., and H.E.F. have no disclosures. GT: Fresenius MC, Abiogen, MG: Vifor CSL: Advisory Board, Consultant; BD: Trial Committee; Sanofi Genzyme: Advisory Board; Honoraria as a speaker in meetings, from CME providers, at the national (Italian) and international level—sponsors of such meetings in the past 3 years have been: AstraZeneca, Baxter/Vantive, BD, Sanofi, and Vifor CSL; Editor-in-Chief of Journal of Vascular Access (SAGE Publishing); Member of the Board of Directors for Project for People (Italian NGO: www.projectforpeople.org/); Partner in a University of Milan simulation training start-up company, Huvant (https://huvant.com/), MF: Amgen, Abiogen, Omega Pharma, Vifor, TLN: Amgen: Speaker; Grant Support; Advisory Board; IntasPharma: Speaker.

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References

    1. Nikkel LE, Hollenbeak CS, Fox EJ, Uemura T, Ghahramani N. Risk of fractures after renal transplantation in the United States. Transplantation. 2009;87(12):1846–1851. 10.1097/TP.0b013e3181a6bbda - DOI - PubMed
    1. Iseri K, Carrero JJ, Evans M, et al. Fractures after kidney transplantation: incidence, predictors, and association with mortality. Bone. 2020;140:115554. 10.1016/j.bone.2020.115554 - DOI - PubMed
    1. Evenepoel P, Claes K, Meijers B, et al. Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients. Kidney Int. 2019;95(6):1461–1470. 10.1016/j.kint.2018.12.024 - DOI - PubMed
    1. Julian BA, Laskow DA, Dubovsky J, Dubovsky EV, Curtis JJ, Quarles LD. Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med. 1991;325(8):544–550. 10.1056/NEJM199108223250804 - DOI - PubMed
    1. Kuppachi S, Cheungpasitporn W, Li R, et al. Kidney transplantation, immunosuppression and the risk of fracture: clinical and economic implications. Kidney Med. 2022;4(6):100474. 10.1016/j.xkme.2022.100474 - DOI - PMC - PubMed

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