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

Abstract

Background Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones and short stature. Recently, a positive association was found between serum 25‐hydroxyvitamin D (25OHD) concentrations and lumbar spine areal bone mineral density (LS‐aBMD) z‐scores in this population. Objectives: To assess whether high‐dose vitamin D supplementation (2000 IU) will result in significantly higher LS‐aBMD z‐scores after one‐year; and to evaluate the effect of vitamin D supplementation on lower limb muscle power. Results: At baseline, average serum 25OHD concentration was 65.6 nmol/L (SD 20.4) with no difference seen between treatment groups (p=0.77). Deficient serum 25OHD concentrations (<50 nmol/L) were measured in only 21% of patients at baseline. Supplementation resulted in higher serum 25OHD concentrations in almost all participants (90%) with significantly higher increases seen with 2000 IU (mean [95% C.I.] = 30.5 nmol/L [21.3; 39.6] vs 15.2 nmol/L [6.4; 24.1], p= 0.02). No significant changes were detected in BMD measurements or in lower limb muscle power between treatment groups from baseline to final visit. Conclusions Supplementation with either 400 or 2000 IU of vitamin D translates into significant increases in serum 25OHD concentrations in children with OI. However, increases in baseline serum 25OHD concentrations already within a healthy range (蠅50 nmol/L) do not translate into increases in BMD z‐scores in children with OI. This research was supported by the Shriners Hospital for Children as well as by The Network for Oral and Bone Health Research.

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

“…Ensuring adequate vitamin D intake is often recommended, but how much vitamin D intake is needed in OI is not well‐established. A recent randomized controlled trial compared two doses of vitamin D supplementation, 400 IU and 2000 IU, in 60 children with OI, most of whom were vitamin D sufficient at baseline [mean serum 25(OH) vitamin D concentration: 67 nmol/L] . No differences in lumbar spine areal BMD or any other outcome measures other than 25(OH) vitamin D serum levels were found between the two doses of vitamin D supplementation.…”

Genetische Ursachen und Therapie der Osteogenesis imperfecta

“…anzustrebender Serumspiegel bei OI ist vergleichsweise überschaubar. Eine vergleichende doppelblinde RCT bei Kindern und Jugendlichen im Alter 6-19 Jahre über ein Jahr zeigt, dass mit 2000 IE täglich im Vergleich zu 400 IE täglich zwar ein signifikant stärkerer Anstieg der Serumspiegel erzielt wird, sich daraus aber zumindest über den Zeitraum von 12 Monaten kein signifikanter Unterschied in der Knochenflächendichte oder der Frakturrate ergibt [19]. Behandlung von Kindern und Jugendlichen:…”

Pharmacological and biological therapeutic strategies for osteogenesis imperfecta

“…In pediatric patients with OI, serum levels of 25‐hydroxyvitamin D were positively correlated with BMD [Edouard et al, ]. However, high‐dose vitamin D (2000 IU) did not prove to be superior to low‐dose vitamin D (400 IU) in increasing lumbar spine bone density [Plante et al, ]. As OI patients are often small‐for‐age, weight and height should be considered when adjusting the dose of supplements to prevent potential side effects (primarily hypercalciuria).…”