Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
Condition: Osteogenesis Imperfecta
MeSH terms: Osteogenesis Imperfecta
Study type: Interventional
Phase: Phase 4

Summary: 
      -  Overall Objective: To test the hypothesis that oral vitamin D supplementation at higher
           than currently prescribed doses has a beneficial effect on the skeleton of young
           patients with osteogenesis imperfecta (OI).

        -  Specific Aims: 1. To determine whether 12 months of high-dose vitamin D supplementation,
           compared to standard-dose vitamin D supplementation, increases areal bone mineral
           density z-scores at the lumbar spine. 2. To examine the effectiveness of high-dose
           vitamin D supplementation to increase trabecular and cortical bone mineral density at
           the radius. 3. To examine whether high-dose vitamin D supplementation has an effect on
           physiological determinants of bone mass (parathyroid hormone, activity of bone
           metabolism, muscle function).

        -  Background: In a preliminary cross-sectional study of 282 OI patients we observed an
           inverse relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels
           and a positive relationship between circulating levels of 25-hydroxyvitamin D and lumbar
           spine areal bone mineral density z-scores. This suggested that high-dose vitamin D
           supplementation would have a beneficial effect on bone density. Most OI patients
           currently receive oral vitamin D supplementation of 400 International Units per day, but
           doses of 2000 International Units per day are safe and have been shown to be beneficial
           in studies on healthy adolescents.

        -  Study Design: This is a parallel-group double-blind randomized controlled trial of 12
           months duration on 60 children and adolescents aged 6 to 19 years with a clinical
           diagnosis of OI. One group of 30 participants will be randomized to receive vitamin D3
           at a dose of 2000 international units per day ('high-dose group'). The other group of 30
           participants will be randomized to receive vitamin D3 at a dose of 400 international
           units per day ('standard-dose group'). Randomization will be stratified according to
           pubertal status and bisphosphonate treatment status.

        -  Clinical Relevance: The proposed study aims at direct improvements in the care of OI
           patients. If a simple and low-cost 'intervention' such as high-dose vitamin D
           supplementation can be shown to be effective in relieving some of the disease burden
           associated with OI, the benefit to OI patients worldwide would be substantial.
    


Intervention name(s): standard-dose vitamin D (400IU per day); high-dose vitamin D (2000 IU per day)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: osteogenesis imperfecta; high-dose vitamin D; bone density; muscle function