Do Glucocorticosteroids Alter Vitamin D Status? A Systematic Review with Meta-Analyses of Observational Studies

Context: Vitamin D supplementation is an important adjunct therapy for the prevention and management of glucocorticoid-induced osteoporosis. There has been little exploration of the relationship between glucocorticosteroid (GCS) use and serum 25-hydroxyvitamin D [25(OH)D]. Objective: The aim of this study was to systematically explore how serum 25(OH)D is altered in adult patients receiving GCS. Data Sources: We reviewed Medline and Cinahl databases between January 1970 and August 2011. Study Selection: Experimental studies were included where 25(OH)D was measured in patients more than 18 yr of age receiving GCS therapy. Studies were excluded if patients received at least 400 IU/d (10 μg/d) vitamin D, if GCS treatment was less than 2-wk duration, if more than 50% of the study population received GCS for renal or hepatic disease or after transplant, or if the study population included patients with Cushing's syndrome. A consensus method was used to classify studies. Of identified studies, 3% met the selection criteria. Data Extraction: Data were extracted by a single author. Study quality was assessed using criteria developed by the American Dietetic Association. Data Synthesis: The weighted mean 25(OH)D (by sample size or sd) was 22.4 [95% confidence interval (CI), 19.4, 25.3] ng/ml and 21.0 (95% CI, 13.5, 28.5) ng/ml, respectively. Random effects meta-analysis was used to compare serum 25(OH)D in patients treated with GCS compared to steroid-naive controls (either healthy or with active disease) and in patients before and after GCS administration. Serum 25(OH)D in GCS users was on average −0.5 (95% CI, −1.0, −0.1) ng/ml lower than in healthy controls (P = 0.03; I2 = 56.4%). Serum 25(OH)D did not differ between GCS users and disease controls [standardized mean difference = 0.0 (95% CI, −0.2, 0.3) ng/ml; P = 0.793; I2 = 16.2%]. Conclusion: The suboptimal concentrations of serum 25(OH)D found in adults receiving GCS are inadequate for prevention and management of glucocorticoid-induced osteoporosis. Recommendations for vitamin D supplementation should be adjusted accordingly.