Circulating Cytokine Levels in Osteoporotic and Normal Women

Interleukin-1 (IL-1) and IL-6 have been postulated to play roles in the pathogenesis of postmenopausal osteoporosis. To test this hypothesis, we measured circulating levels of IL-6, IL-1 alpha, and IL-1 beta in 40 age-matched normal and 40 osteoporotic women with vertebral fractures and increased bone turnover. Since IL-1 activity is modulated by the IL-1 receptor antagonist (IL-1ra), we also measured circulating IL-1ra levels in these women. Despite having higher rates of bone turnover as assessed by bone biochemical markers, the osteoporotic women had serum levels of IL-6, IL-1 alpha, and IL-1 beta that were similar to the normal women. IL-1ra levels (mean +/- SEM) tended to be lower in the osteoporotic women (143 +/- 21 pg/mL) vs. the normal women (189 +/- 22 pg/mL; P = 0.08). The IL-1 alpha/IL-1ra ratio, an index of IL-1 alpha bioactivity, was higher in the osteoporotic women (6.4 +/- 1.1) than in the normal women (4.4 +/- 0.5; P < 0.05). There were nonsignificant trends for increased IL-1 beta/IL-1ra and (IL-1 alpha + IL-1 beta)/IL-1ra ratios in the osteoporotic vs. normal women. None of the cytokines correlated with markers of bone resorption in either group of women. In summary, although there was a trend for a higher IL-1/IL-1ra ratio in the osteoporotic women, we were unable to demonstrate unequivocal abnormalities of cytokines affecting bone resorption in peripheral serum of women with postmenopausal osteoporosis. However, it is possible that increased production of these cytokines occurs in the local environment of bone or bone marrow and is not detected by analysis of peripheral serum. Thus, further studies will be required to exclude this possibility.