Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Condition: Rheumatoid Arthritis; Hypovitaminosis D
MeSH terms: Arthritis; Arthritis, Rheumatoid; Rickets; Avitaminosis; Vitamin D Deficiency
Study type: Interventional

Summary: 
      This study recruits individuals with rheumatoid arthritis (RA) and low vitamin D
      concentrations. Subjects are dosed with vitamin D or placebo for one year. Primary outcome is
      change in bone turnover markers, additionally, bone mineral density and parameters of RA
      status are evaluated throughout the study.
    

Detailed description: 
      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 [6].
      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 [9] and pain levels [10]. By contrast, an eight-week open-label
      study [11] 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 [12] 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 [14] 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 [15], 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 [15]. Likewise, vitamin D and calcium did not
      prevent bone loss in a prospective cohort study of patients with RA [13]. 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 [15], 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.
    

Intervention name(s): Vitamin D; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Ergocalciferol 50,000 IU loading dose then twice monthly for one year; matching placebo
Other intervention name(s): ergocalciferol
Intervention MeSH terms: Vitamin D; Ergocalciferols
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: rheumatoid arthritis; hypovitaminosis D; bone turnover; ergocalciferol