Three-monthly bolus vitamin D supplements (1000 vs 400 IU/day) for prevention of bone loss in children with difficult-to-treat nephrotic syndrome: a randomised clinical trial.

BACKGROUND: Nephrotic syndrome (NS) in children is one of the most common chronic diseases with a remitting and relapsing course. Glucocorticoids (prednisolone) are considered to be the treatment of choice but are associated with osteoporosis. There are no uniform consensus guidelines regarding the optimum dose of calcium and vitamin D for osteoprotection. Some authorities suggest a daily dose of 1000 IU vitamin D for children for osteoprotection, while others suggest a daily dose of 400 IU. OBJECTIVES: To compare the efficacy of three-monthly bolus vitamin D supplementation (1000 vs 400 IU/day) to prevent bone loss in children with difficult-to-treat NS (DTNS). METHODS: In this parallel-group, open-label, randomised clinical trial, 60 children aged 1-18 years with DTNS [37 with frequently relapsing NS (FRNS), 13 steroid-dependent NS (SDNS) and 10 steroid-resistant NS (SRNS)] were enrolled and block randomised in a 1:1 allocation ratio to receive 1000 IU/day vitamin D (Group A, n = 30) or 400 IU/day (Group B, n = 30), administered as three-monthly bolus supplemental doses. In Group A, vitamin D (cholecalciferol, Calcirol®sachet) was administered as a stat dose of 90,000 IU every three months (calculated for a period of three months at 1000 IU/day). In Group B, vitamin D (cholecalciferol) was administered as a stat dose of 36,000 IU every three months (calculated for a period of three months at 400 IU/day). The proportionate change in bone mineral content (BMC) was studied by dual energy X-ray absorptiometry (DEXA) scan in both groups after vitamin D supplementation by analysing the values of BMC obtained 12 months apart (baseline vs. after 12 months). RESULTS: Sixty children were randomised to receive vitamin D at a dose of either 1000 IU/day (Group A) or 400 IU/day (Group B). The two groups were comparable in their baseline clinical and laboratory parameters (including BMC and bone mineral density (BMD)). The distribution of the three types of NS (FRNS, SDNS and SRNS) was also comparable in both groups. In Group A, there were 19, 6 and 5 children with FRNS, SDNS and SRNS, respectively, and in Group B there were 18, 7 and 5 children with FRNS, SDNS and SRNS, respectively. The proportionate change in BMC was not significantly different between the two groups (median proportionate change in BMC in Group A 13.36% vs 11.59% in Group B, p = 0.22). Overall, BMC increased in both groups (96.7% in each). Only one (3.3%) patient in each group exhibited bone loss. None of the patients had a urinary calcium:creatinine ratio >0.2 at the end of the study. CONCLUSION: Three-monthly bolus vitamin D dosing regimens administered either as 1000 or 400 IU/day prevent bone loss in children with DTNS who require long-term steroids. Overall, three-monthly bolus supplemental prophylactic vitamin D, either 1000 or 400 IU/day, would seem to be an effective strategy for preventing bone loss in children with DTNS, as evidenced by the extremely low rates of bone loss (3.3% in each group), and is useful for delivering optimal care to children with DTNS. However, since this study was designed as an equivalence trial and not a superiority trial, further studies are required to demonstrate the superiority of the former regimen over the latter. ABBREVIATIONS: BMC, bone mineral content; BMD, bone mineral density; DEXA, dual energy X-ray absorptiometry; DTNS, difficult-to-treat nephrotic syndrome; FRNS, frequently relapsing nephrotic syndrome; IFRNS, infrequently relapsing nephrotic syndrome; iPTH, intact parathyroid hormone; NS, nephrotic syndrome; SDNS, steroid-dependent nephrotic syndrome; SRNS steroid-resistant nephrotic syndrome.