Secondary hyperparathyroidism promotes the acute phase response -- a rationale for supplemental vitamin D in prevention of vascular events in the elderly

Abstract

Parathyroid hormone (PTH) promotes IL-6 secretion by osteoblasts, and may also up-regulate IL-6 production in the liver and adipose tissue; this may explain why serum IL-6 is markedly elevated in primary hyperparathyroidism, and low in hypoparathyroidism. IL-6 is the chief stimulus to hepatic production of many acute phase reactants, notably fibrinogen and C-reactive protein (CRP). Mild secondary hyperparathyroidism is common in elderly people, particularly at high latitudes during the winter, owing to poor vitamin D status. This may rationalize evidence that acute phase proteins show seasonal variations and are typically elevated in the elderly, whereas leisure physical activity is associated with a reduction in these proteins. In a recent clinical trial targeting elderly chronically ill patients, administration of vitamin D reduced serum levels of both CRP and IL-6; further such studies should assess the impact of physiologically meaningful doses of vitamin D on acute phase reactants in elderly subjects likely to have poor vitamin D status. Since elevations of CRP and fibrinogen may increase risk for thromboembolic vascular events, these considerations may help to explain the excess of coronary mortality observed during winter months, and suggest a role for supplemental vitamin D in preservation of vascular health. Moderate alcohol intake is associated with reduced serum PTH as well as decreased levels of CRP and fibrinogen; conceivably, modulation of PTH mediates, at least in part, the favorable impact of moderate drinking on the acute phase reactants.