Hypovitaminosis D and response to cholecalciferol supplementation in patients with autoimmune and non-autoimmune rheumatic diseases

Abstract

Recent reports suggest a role of hypovitaminosis D in the pathogenesis of inflammatory autoimmune diseases (ARD); we investigated 25(OH)vitamin D plasma level before and after supplementation in ARD and NARD (non-ARD: osteoporosis and/or OA) patients. We retrospectively evaluated 572 consecutive clinical records of adult patients at immuno-rheumatology and rehabilitative units of our institution from January 2006 to October 2009. We excluded patients with vitamin D supplementation or renal failure, primary hyperparathyroidism, liver failure. We recorded 25(OH)vitamin D plasma concentration of 245 patients together with other clinical data. We then evaluated 25(OH)vitamin D plasma concentration of 100 (43 ARD and 57 NARD) patients previously included who underwent 750-1,000 UI/die 25(OH)vitamin D supplementation for at least 6 months. Appropriate statistical analysis was performed. The median 25(OH)vitamin D concentration was not significantly different between 119 ARD [33.4 (IQR 22.5-54.9) nmol/l] and 126 NARD patients 32.9 (IQR 18.7-50.2). In stepwise logistic regression, female sex (F:13.7), winter-spring season (F:5.6) and older age (F:5.3), but not ARD, predicted plasma 25(OH)vitamin D <75 nmol/l. Cholecalciferol supplementation increased 25(OH)vitamin D plasma concentration equally in both ARD and NARD; however, only 29/100 patients reached a plasma level ≥75 nmol/l without differences between ARD and NARD (χ(2) = n.s.). Hypovitaminosis D is common in rheumatic patients. Sex and age but not ARD are risk factors for this condition. 750-1,000 UI/die of cholecalciferol is not sufficient to normalize plasma level in these patients. Increase of plasma 25(OH)vitamin D after treatment is not influenced by the presence of an inflammatory autoimmune disease.

Vitamin D Status Is Associated with Disease Activity among Rheumatology Outpatients

“…Meanwhile, similar year-around levels of supplement intake between the case and control group (1000 IU), but different mean and median 25(OH)D may indicate different requirements for this specific clinical population who are suffering from SARD. Sainaghi et al [19] evaluating 25(OH)D plasma concentration of 245 patients SARD and non-SARD groups, report the 750–1000 IU/day vitamin D might not be enough to provide minimum optimal 25(OH)D concentration of ≥75 nmol in this clinical population. Based on recent evidence, Holick [6] suggests daily vitamin D intake of 1500–2000 IU for healthy adults in general population.…”

“…A meta-analyses reported vitamin D receptor polymorphism in RA and SLE, although only a few existing studies were analysed [21]. Others emphasised the impact of vitamin D on disease activity and elucidated the mechanisms [7,8,9,19,22]. Our evaluation of current evidence identified the following gaps in research:

Vitamin D receptor polymorphism and SARDs, and role of ethnicity in association between vitamin D and SARDs;

Differences in vitamin D requirements between SARD cases and the general population as well as the requirements for individuals who are at risk of SARD and individuals with established SARD;

Mechanisms of the impact of vitamin D in different pathways in immune system;

The potential interaction between vitamin D and drugs in SARD cases and optimal supplementation approaches.

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Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

“…58 In fact, a lower dietary intake of vitamin D has been linked to a higher risk of RA development in a metaanalysis of several studies 59 ; furthermore, plasma 25(OH)D concentration has been reported to be lower in RA patients when compared to healthy controls, 60 although these results were not confirmed in other studies. 61 Plasma 25(OH)D concentration has also been inversely correlated with disease activity. 59,62 Further evidence for an involvement of vitamin D metabolism in the pathogenesis of RA is based on the following observations, suggesting a local action for vitamin D metabolites in the modulation of joint inflammation:…”

“…66 The importance of understanding the role of vitamin D in autoimmune diseases is enforced by the very high prevalence of hypovitaminosis D in this particular setting. 61,67 Relative hypovitaminosis D and secondary hyperparathyroidism in autoimmune rheumatic diseases An impairment of Vitamin D system has already been postulated as a concausal factor in the pathogenesis of osteoporosis in inflammatory arthritis. In fact, a VDR polymorphism has been linked to bone loss in RA; in particular 68 Rass and colleagues found a lower BMD in RA patients carrying the BB and Bb genotypes of the VDR BsmI polymorphism with respect to carriers of the bb genotype.…”

Vitamin D, inflammatory markers, steroid use and systemic factors: which is the culprit in rheumatoid arthritis associated osteoporosis?

“…In fact, a lower dietary intake of vitamin D has been linked to a higher risk of RA development in a meta-analysis of several studies [9]; furthermore, plasma 25 (OH) D concentrations has been reported to be lower in RA patients when compared to healthy control [10] although these results were not confirmed in other studies [11]. Vitamin D has also been inversely correlated with disease activity [9,12].…”