300,000 IU or 600,000 IU of Oral Vitamin D3 for Treatment of Nutritional Rickets: A Randomized Controlled Trial.

ABSTRACT

Objective: To evaluate the non-inferiority of a lower therapeutic dose (300,000 IU) in comparison to standard dose (600,000) IU of Vitamin D for increasing serum 25(OH) D levels and achieving radiological recovery in nutritional rickets. Design: Randomized, open-labeled, controlled trial. Setting: Tertiary care hospital. Participants: 76 children (median age 12 mo) with clinical and radiologically confirmed rickets. Intervention Oral vitamin D3 as 300,000 IU (Group 1; n=38) or 600,000 IU (Group 2; n=38) in a single day. Outcome variables Primary Serum 25(OH)D, 12 weeks after administration of vitamin D3; Secondary Radiological healing and serum parathormone at 12 weeks; and clinical and biochemical adverse effects. Results: Serum 25(OH)D levels [geometric mean (95% CI)] increased significantly from baseline to 12 weeks after therapy in both the groups [Group 1 7.58 (5.50–10.44) to 16.06 (12.71– 20.29) ng/mL, P<0.001]; Group 2 6.57 (4.66–9.25) to 17.60 (13.71–22.60, P<0.001]. The adjusted ratio of geometric mean serum 25(OH)D levels at 12 weeks between the groups (taking baseline value as co-variate) was 0.91 (95% CI 0.65–1.29). Radiological healing occurred in all children by 12 weeks. Both groups demonstrated significant (P<0.05) and comparable fall in the serum parathormone and alkaline phosphatase levels at 12 weeks. Relative change [ratio of geometric mean (95% CI)] in serum PTH and alkaline phosphatase, 12 weeks after therapy, were 0.98 (0.7–1.47) and 0.92 (0.72–1.19), respectively. The serum 25(OH)D levels were deficient (<20 ng/mL) in 63% (38/60) children after 12 weeks of intervention [Group 1 20/32 (62.5%); Group 2 18/28 (64.3%)]. No major clinical adverse effects were noticed in any of the children. Hypercalcemia was documented in 2 children at 4 weeks (1 in each Group) and 3 children at 12 weeks (1 in Group 1 and 2 in Group 2). None of the participants had hypercalciuria or hypervitaminosis D. Conclusion: A dose of 300,000 IU of vitamin D3 is comparable to 600,000 IU, administered orally, over a single day, for treating rickets in under-five children although there is an unacceptably high risk of hypercalcemia in both groups. None of the regime is effective in normalization of vitamin D status in majority of patients, 3 months after administering the therapeutic dose.