Osteogenesis Imperfecta
Conditions
Keywords
osteogenesis imperfecta, high-dose vitamin D, bone density, muscle function
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.
Interventions
DIETARY_SUPPLEMENTstandard-dose vitamin D (400IU per day)
DIETARY_SUPPLEMENThigh-dose vitamin D (2000 IU per day)
Sponsors
Louis-Nicolas Veilleux Ph.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of OI of any type.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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'). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in lower extremity muscle power per body weight, as measured by jumping mechanography, relative to baseline. | baseline and 12 months | A countermovement jump to maximal height ('single two-legged jump') will be evaluated. In patients who are unable to jump, the heel-rise test will be used to determine muscle power. |
Countries
Canada
Outcome results
None listed