Treatment of Hypovitaminosis D in Rheumatoid Arthritis

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.

Inclusion Criteria:

- Rheumatology

Exclusion Criteria:

- Bisphosphonate therapy