Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial.

Randomized controlled trial in children and adolescents with osteogenesis imperfecta aged 6 to 19 years, recruited at Shriners Hospital for Children in Montreal, Canada. Most participants had OI type III or IV, and many were receiving long-term bisphosphonate therapy.

Oral vitamin D3 was given for 12 months at either 400 IU/day or 2000 IU/day. The high-dose arm received two 1000 IU pills daily, while the low-dose arm received one 400 IU pill plus one placebo daily; compliance was verified by pill count.

Higher-dose vitamin D increased serum 25-hydroxyvitamin D, but did not improve bone density, bone turnover, or muscle outcomes over 12 months. LS-aBMD z-score change was 0.0 in the 400 IU group versus 0.1 in the 2000 IU group (p=0.63), and radius trabecular vBMD z-score change was -1.0 versus -0.4 (p=0.22). Serum 25OHD increased more with 2000 IU/day than with 400 IU/day (30.5 vs 15.2, p=0.02), but mechanography, PTH, PINP, CTX, and fracture outcomes were not significantly different. Vitamin D3 at 2000 IU/day was reported as safe, with no hypercalcemia, no hypercalciuria, and no serious adverse events.

The study was limited by its 12-month duration and the lack of a meaningful effect on the primary skeletal outcome despite improved vitamin D status. Most participants had baseline vitamin D within the recommended range, which may have reduced the chance of benefit, and a possible signal in the small subgroup with very low baseline 25OHD was not conclusive. Generalizability is also limited by the specific pediatric osteogenesis imperfecta population, most of whom were on bisphosphonate therapy.