« Back

Vitamin D deficiency commonly underlies initiation, progression of rheumatologic disorders

Thursday, October 30 2008 | Comments

---

What's This? By David MacDougall

Vitamin D deficiency may be a common underlying factor in the initiation and progression of rheumatoid arthritis (RA) and other rheumatologic disorders, according to Dr. Ann Cranney with the division of rheumatology at The Ottawa Hospital.

Studies of vitamin D deficiency have yielded variable estimates of the prevalence of this condition and have been characterized by differences in study populations, seasonal and geographic factors, and criteria for the measurement of serum levels of 25-hydroxy vitamin D (25-OH-D), the accepted marker for vitamin D nutritional status, Dr. Cranney said. Increased awareness of the importance of suboptimal vitamin D status has resulted in an 80% to 90% increase in ordering of 25-OH-D assays in some reference laboratories during the past year, she noted.

In the National Health and Nutrition Examination Survey, the prevalence of vitamin D deficiency (defined as serum 25-OH-D <25 ng/mL) ranged from 25% to 57%, Dr. Cranney explained. Higher rates of vitamin D deficiency were observed in women and non-Hispanic black people, and an inverse association was observed between serum 25-OH-D concentrations and body mass index.

Cross-sectional studies have demonstrated an association between lower serum 25-OH-D levels and chronic musculoskeletal pain, Dr. Cranney said. In a study of 150 patients who presented with persistent, nonspecific musculoskeletal pain, 140 patients (93%) had deficient levels of vitamin D. Of all the patients, 28% (42/150) had severely deficient vitamin D levels (<=8 ng/mL), including 55% of those aged younger than 30 years. A birth cohort study of 9,377 persons born in 1958 found that chronic widespread pain was associated with current vitamin D status in women but not in men after adjustment for social and lifestyle factors.

Low vitamin D levels are not associated with diffuse musculoskeletal pain, and treatment with vitamin D does not reduce pain in patients with diffuse pain who have low vitamin D levels, she noted. In a study of 184 patients with diffuse pain and 104 patients with osteoarthritis, mean serum 25-OH-D levels and the proportion of patients with low serum 25-OH-D levels (<20 ng/mL) were similar in both groups. Vitamin D supplementation for 3 months had no effect on pain in 50 patients who had diffuse pain and serum 25-OH-D <20 ng/mL.

Vitamin D is an important immune system regulator, Dr. Cranney said, and the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has been shown to inhibit the development of certain autoimmune diseases including inflammatory bowel disease. The immunomodulatory effects of 1,25(OH)2D3 include inhibition of the maturation and survival of dendritic cells and the production of interleukin-12 and tumor necrosis factor-alpha.

"Suboptimal 25-OH-D concentrations may affect the initiation and propagation of autoimmune diseases, so vitamin D treatment could delay the onset of disease and modulate disease activity," Dr. Cranney commented.

The metabolism of vitamin D may be altered in patients with rheumatic disease due to decreased synthesis associated with avoidance of sun exposure and impaired mobility, concurrent renal disease, and the use of medications known to influence the metabolism of vitamin D including corticosteroids and hydroxychloroquine, Dr. Cranney said. Antibodies to vitamin D have been detected in patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome, and other autoimmune diseases, she noted.

Vitamin D intake is inversely associated with the risk of RA in women, according to an analysis of data from the Iowa Women's Health Study, a prospective cohort study of 29,368 women aged 55 to 69 years without a history of RA at baseline. During 11 years of follow-up, greater intake (highest vs lowest tertile) of vitamin D was inversely associated with risk of RA (relative risk, 0.67; P=.05 for trend). Inverse associations were observed for both dietary and supplemental vitamin D.

An association between vitamin D metabolite levels and disease activity was observed in a study of 206 patients with inflammatory polyarthritis. At baseline there was an inverse association between 25-OH-D levels and swollen and tender joint counts, Health Assessment Questionnaire (HAQ) scores, C-reactive protein levels, and Disease Activity Score 28-joint assessment (DAS28) scores. Higher baseline 25-OH-D levels were associated with lower HAQ scores after 1 year of follow-up.

"25-OH-D may influence disease activity in early inflammatory arthritis," Dr. Cranney added. "The evidence on whether vitamin D is a factor in the initiation of RA is conflicting."

Experimental evidence suggests that 1,25(OH)2D3 may inhibit B cell proliferation, and that treatment with vitamin D metabolites may have beneficial effects in animal models of SLE, Dr. Cranney said. An analysis of serum 25-OH-D levels in 123 patients with recently diagnosed SLE and 240 matched controls revealed a trend toward lower 25-OH-D levels in cases as compared with controls, which was statistically significant in white patients (P=.04) after controlling for age, sex, season, and smoking. Overall, 67% of the patients with SLE were vitamin D deficient, with mean levels significantly lower among black patients (15.9 ng/mL) as compared with white patients (31.3 ng/mL). Critically low vitamin D levels (<10 ng/mL) were found in 22 patients with SLE.

"Some studies suggest an inverse association between 25-OH-D levels and disease activity in SLE," Dr. Cranney said. "Most studies did not avoid the confounding effects of disease duration."

Print  |  E-mail