Low Dose Versus High Dose Vitamin D for Treatment of Nutritional Rickets: A Systematic Review and Meta-analysis

Nutritional rickets is caused by vitamin D deficiency, and/or inadequate dietary calcium, and/or phosphate intake. There is considerable variation in the therapeutic vitamin D dosing regimens for nutritional rickets, and the comparative efficacy of low-dose versus high-dose regimens is unclear.

To determine the efficacy and safety of low-dose (≤ 300,000 IU) versus high-dose (300,000-600,000 IU) vitamin D regimens for the treatment of nutritional rickets in children.

We systematically searched PubMed, the Cochrane Library, EMBASE, Web of Science, Scopus, grey literature sources, and clinical trial registries till April 1, 2025 (without language restrictions), for randomized controlled trials or quasi-randomized trials in children < 18 years with nutritional rickets. A three-step approach determined the study eligibility. Two reviewers independently screened studies, extracted data and assessed the risk of bias. Odds ratios, and mean differences with 95% confidence intervals were calculated. Certainty of evidence was assessed using the GRADE approach.

Four studies met the inclusion criteria. The pooled mean difference in serum 25(OH)D levels at 12 weeks between the low-dose and high-dose groups was - 2.27 ng/mL (95% CI - 7.64, 3.10; P = 0.41). Radiological improvement (reduction in Thacher score from severe to mild/moderate) showed pooled OR 0.38 (95% CI 0.01, 10.20; P = 0.57). Other outcomes, including a reduction in serum parathyroid hormone and serum alkaline phosphatase levels at 12 weeks were also comparable. No serious clinical adverse events were reported.

No statistically significant or clinically meaningful differences were found among children with nutritional rickets, receiving low-dose and high-dose vitamin D regimens.