In vitro studies have shown that 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] decreases cytokine production by monocytes and lymphocytes. In addition, intravenous or oral pulse calcitriol treatment suppresses interleukin 6 (IL6) and interleukin1beta (IL1beta) in hemodialysis patients. We studied the effect of a daily 12-week course of 1000 mg calcium and 800 U cholecalciferol on circulating 25 hydroxyvitamin D [25(OH)D], PTH, cytokines, osteoprotegerin (OPG), C-reactive protein (CRP), bone markers, lipid parameters and insulin levels in 47 healthy post-menopausal women. Thirty-nine women completed the study. A significant increase in 25(OH)D and a significant decrease in PTH were observed (p=0.0043 and p<0.0001, respectively). In addition, alkaline phosphatase, osteocalcin and, to a lesser extent, urinary free deoxypiridinoline (DPD) decreased significantly (p<0.0001, p=0.0002 and p=0.026, respectively). No change in circulating IL6, tumor necrosis factor alpha (TNFalpha), CRP, OPG, triglycerides, LDL- and HDL-cholesterol, and insulin levels was observed. Correlation studies in the 47 women enrolled in the study revealed inverse significant correlations between OPG on one side and body mass index, LDL-cholesterol, IL6, CRP and insulin levels on the other (p=0.002, p=0.002, p=0.004, p=0.023 and p=0.0001). Also, IL6 was significantly correlated with insulin levels (p=0.0005). In a multivariate model, both insulin and LDL-cholesterol were independently associated with OPG, while only insulin was independently associated with IL6. Our results showed no effect of a short-term calcium-vitamin D treatment on circulating cytokines, CRP, insulin levels and lipid parameters. This could be related to the low circulating cytokine concentrations in healthy subjects or to the short duration of treatment. The interesting association we found between OPG and some cardiovascular risk markers deserves further investigation.