Treatment of Hypovitaminosis D in Rheumatoid Arthritis
|Rheumatoid Arthritis Hypovitaminosis D||Dietary Supplement: Vitamin D Dietary Supplement: placebo|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Treatment of Hypovitaminosis D in Rheumatoid Arthritis|
- Parathyroid Hormone Level [ Time Frame: 1 Year ]Serum parathyroid hormone level
- Bone Mineral Density [ Time Frame: 1 Year ]one year change in mean total hip BMD
- Short Form 36 Survey [ Time Frame: 1 Year ]12 month score for physical function domain of SF36 survey; scale 0 to 100 with 0 indicating worst disability and 100 indicating best physical function
|Study Start Date:||February 2005|
|Study Completion Date:||February 2009|
|Primary Completion Date:||August 2008 (Final data collection date for primary outcome measure)|
Active Comparator: vitamin D
ergocalciferol 50,000 IU Twice monthly
Dietary Supplement: Vitamin D
Ergocalciferol 50,000 IU loading dose then twice monthly for one year
Other Name: ergocalciferol
Placebo Comparator: placebo
matching placebo tablet
Dietary Supplement: placebo
Osteoporosis is twice as common in people with rheumatoid arthritis (RA), compared to age and gender-matched controls [1, 2]. Hypovitaminosis D can contribute to osteoporosis pathogenesis by decreasing calcium absorption, leading to a decline in serum ionized calcium, a rise in parathyroid hormone levels and upregulation of osteoclast activity, leading to loss of calcium from the skeleton. Hypovitaminosis D is also common in patients with rheumatoid arthritis [3-5], making it an appealing target to potentially improve health in both RA and osteoporosis.
Vitamin D has theoretic potential to modulate RA disease activity, based on the presence of vitamin D receptors in lymphocytes, macrophages, chondrocytes, and synovial cells . Vitamin D, given as the bioactive metabolite 1,25(OH)2D, ameliorates disease activity in murine models of RA [7, 8]. However, few studies have evaluated the effect of vitamin D on RA disease activity in humans. Two three month open-label studies reported that vitamin D reduced RA disease activity  and pain levels . By contrast, an eight-week open-label study  reported no reduction in swollen joint counts, inflammatory markers or cytokine levels after vitamin D therapy. The only double-blind, placebo-controlled trial published thus far  found no significant effect of vitamin D on RA disease activity, but was limited by the lack of hypovitaminosis D as a criterion for study entry. Indeed, at baseline subjects' mean 25(OH)D levels indicated vitamin D repletion, potentially explaining the null effect of vitamin D on RA disease activity.
Three studies have evaluated the effect of vitamin D on bone mineral density (BMD) in patients with RA [13-15]. Researchers  randomized 96 subjects with RA to vitamin D (500 IU/day) and calcium (1000 mg/day) or placebo for two years; vitamin D and calcium therapy modestly increased BMD in the spine and hip. In another study , 20 subjects randomized to daily calcium and 1 α-hydroxyvitamin D for up to 24 months experienced similar declines in radius and spine BMD compared to 15 controls . Likewise, vitamin D and calcium did not prevent bone loss in a prospective cohort study of patients with RA . However, none of the studies required hypovitaminosis D as an entry criterion, vitamin D repletion to 25(OH)D levels > 32 ng/ml were not evaluated [13, 14] or achieved , and low doses of vitamin D were administered, potentially limiting skeletal benefits of this therapy.
We hypothesized that correction of hypovitaminosis D in subjects with RA would decrease parathyroid hormone (PTH), increase BMD, improve functional capacity and down-regulate inflammatory cytokine production, thereby diminishing disease activity. Vitamin D is inexpensive and widely available. If proven beneficial, vitamin D might become a mainstay of therapy for subjects with RA.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00423358
|United States, Wisconsin|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53705|
|Principal Investigator:||Karen E Hansen, MD||University of Wisconsin, Madison|