Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
- Conditions
- Osteogenesis Imperfecta
- Interventions
- Dietary Supplement: standard-dose vitamin D (400IU per day)Dietary Supplement: high-dose vitamin D (2000 IU per day)
- Registration Number
- NCT01713231
- Lead Sponsor
- Louis-Nicolas Veilleux Ph.D.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- Clinical diagnosis of OI of any type.
- Any condition that renders bone density measurements at the lumbar spine impossible. An example for this is prior spinal fusion surgery.
- Bisphosphonate therapy for less than two years duration.
- Use of medication, other than bisphosphonates, known to affect bone metabolism or 25OHD serum concentrations. Examples are anti-epileptics, active vitamin D metabolites, corticosteroids and thyroid hormones.
- Liver and renal disease known to interfere with vitamin D metabolism.
- Any other disorder of calcium and phosphate metabolism (apart from vitamin D deficiency) that might interfere with PTH.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description standard-dose vitamin D standard-dose vitamin D (400IU per day) one group of 30 participants will be randomized to receive vitamin D3 at a dose of 400 international units per day ('standard-dose group'). high-dose vitamin D high-dose vitamin D (2000 IU per day) One group of 30 participants will be randomized to receive vitamin D3 at a dose of 2000 international units per day ('high-dose group').
- Primary Outcome Measures
Name Time Method Change in areal bone mineral density z-score of the lumbar spine at baseline and 12 months LS-aBMD z-score will be used as the primary outcome.The lumbar spine is the standard site of measurement both in the clinical follow up of OI patients .
- Secondary Outcome Measures
Name Time Method Change in trabecular and cortical volumetric bone mineral density z-scores at the radius, as measured by pQCT, relative to baseline. at baseline and at 12 months Trabecular bone is analyzed at the distal radial metaphysis ('4% site'). Cortical bone is analyzed at the radial diaphysis ('65% site').
Trial Locations
- Locations (1)
Shriners Hospitals for Children-Canada
🇨🇦Montréal, Quebec, Canada