Cholecalciferol significantly reduces whole parathyroid hormone (PTH) levels and attenuates bone loss at the lumbar spine compared with placebo among incident kidney transplant recipients (KTRs), according to a study in the Journal of Bone and Mineral Research.
The results are from a prespecified secondary endpoint analysis of a single-center, parallel-arm, randomized, double-blind, placebo-controlled, 11-month trial. All patients received kidney transplantation from a living donor, were aged 20 to 80 years, and had an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2.
Participants received cholecalciferol 4000 IU or a matching placebo daily from 1 to 12 months post-transplant, with a random block size of 8 and stratified by age (<50 or ≥50 years) and sex. Blood and urine samples were obtained at baseline and at 6 and 12 months post-transplant.
A total of 193 patients were randomized to cholecalciferol (n = 96) or placebo (n = 97). Of these patients, 187 (92 patients in the cholecalciferol group and 95 patients in the placebo group) received at least 1 dose of the study drug and were included in the analyses. Participants were median aged 52 years, had a median eGFR level of 46 mL/min/1.73 m2, and a median 25-hydroxyvitamin D (25[OH]D) level of 10 ng/mL. Approximately 70% were men.
At the conclusion of the study period, the placebo group had minimal change in serum 25(OH)D levels (3 ng/mL [95% CI, 2-5]), and the cholecalciferol group had a substantial increase (28 ng/mL [95% CI, 27-30]), resulting in a significant between-group difference of 25 ng/mL (95% CI, 22-28).
The geometric mean for the percentage change in whole PTH levels was –28% (95% CI, –34 to –22) in the placebo group and –39% (95% CI, –44 to –33) in the cholecalciferol group, with a significant between-group difference (–15%; 95% CI, –25 to –3, P = .02). Similar findings were observed in the sensitivity analyses. Cholecalciferol’s effects on whole PTH levels were modified by baseline eGFR, calcium, and 25(OH)D levels, with greater treatment effects found in participants with higher eGFR, lower calcium level, and lower 25(OH)D level (all P value for interaction <.05).
The mean percentage change in lumbar spine bone mineral density (BMD) was –0.2% (95% CI, –1.4 to 0.9) in the cholecalciferol group and –1.9% (95% CI, –3.0 to –0.8) in the placebo group, with a significant between-group difference (1.7%; 95% CI, 0.1 to 3.3; P = .04). The beneficial effect of cholecalciferol on lumbar spine BMD was prominent in patients who had a lower baseline BMD (P for interaction <.05).
Changes in PTH levels from baseline to 12 months post-transplant were associated with changes in lumbar spine BMD (P < .01). The mediation analysis showed that the indirect effect mediated by changes in whole PTH levels was 39% (P = .02).
The study had several limitations. The single-center design included only Japanese KTRs from living donors, which prevents generalizability to wider populations. Most participants had poor vitamin D status at baseline, and more than half of the cohort had normal BMD, which diluted the effect size on BMD in KTRs at high risk for fracture.
“Cholecalciferol supplementation at 4000 IU daily could be a promising regimen for KTRs with vitamin D deficiency,” the study investigators concluded. “This regimen has the potential to eliminate vitamin D deficiency and provides beneficial effects on bone health even under glucocorticoid treatment.”
Tsujita M, Doi Y, Obi Y, et al. Cholecalciferol supplementation attenuates bone loss in incident kidney transplant recipients: a prespecified secondary endpoint analysis of a randomized controlled trial. J Bone Miner Res. Published online November 8, 2021. doi:10.1002/jbmr.4469