Effects of vitamin D supplements on bone metabolism in kidney transplant recipients: a systematic review and meta-analysis

Vitamin D has been reported to decrease parathyroid hormone (PTH), reduce bone loss, and promote calcium absorption. However, its effects on bone metabolism in kidney transplant recipients (KTRs) remain controversial. This review aimed to analyze the effects of vitamin D supplements on bone metabolism in KTRs. We searched PubMed, EMBASE, Web of Science, and the Cochrane Library from inception through September 30, 2023, for randomized controlled trials (RCTs) on the effect of vitamin D on bone metabolism after kidney transplantation. We also searched the reference lists of systematic reviews and included studies. The outcomes were expressed using relative risk (RR) or standardized mean difference (SMD) with the corresponding 95% confidence interval (CI). Fourteen studies involving a total of 985 KTRs were included in this analysis. The treatments consisted vitamin D supplementation at various doses and types. The duration of follow-up ranged from 3 to 12 months. More than half of the 14 studies (n = 8) had an overall high risk of bias, as they had at least one high-risk domain. Compared to placebo or no treatment, vitamin D supplementation significantly improved bone mineral density (BMD) at the femoral neck (SMD 0.54; 95% CI 0.10 to 0.98; P = 0.02), reduced serum PTH level (SMD -0.49; 95% CI -0.76 to -0.22; P = 0.0003), decreased bone alkaline phosphatase (BAP) level (SMD -0.31; 95% CI -0.52 to -0.09; P = 0.006), increased serum calcium level (SMD 0.35; 95% CI 0.12 to 0.58; P = 0.003) and increased the risk of hypercalcemia (RR 1.92; 95% CI 1.23 to 3.01; P = 0.004). After treatment, there were no significant differences in the changes in lumbar spine BMD, 25-hydroxyvitamin D (25OHD) level, serum phosphate level, serum alkaline phosphatase (ALP) level, calciuria level, proteinuria level and estimated glomerular filtration rate (eGFR). No significant differences were observed in the incidence of fracture and acute graft rejection. Vitamin D supplementation does not improve overall BMD or prevent fracture in KTRs. Vitamin D supplementation may effectively reduce serum PTH and BAP level. However, it may also increase the risk of hypercalcemia, necessitating the monitoring of serum calcium level.