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Serum Interleukin 6 Is a Major Predictor of Bone Loss in Women Specific to the First Decade Past Menopause*

Departments of Social Medicine and Clinical Epidemiology (C.S.-N.) and Medicine I, Endocrinology, and Metabolism (C.S.-N., H.B., G.L.-B., H.W., M.J.S., R.Z.), University of Heidelberg Medical Center, D-69115 Heidelberg; and Department of Medicine, Kliniken Bergmannsheil, University of Bochum (J.P.), D-44789 Bochum, Germany

The role of serum interleukin 6 (IL-6) as a predictor of bone loss was examined in a population-based, longitudinal study of 137 postmenopausal German women, 52–80 yr old at baseline. Serum IL-6 and other biochemical parameters were measured in baseline blood or urine specimens. Repeat standardized measures of bone mineral density (BMD) at the femur (total hip) and the lumbar spine (L2–L4) were taken by dual x-ray absorptiometry an average of 3.3 yr apart. Medical history and anthropometric measures were obtained from standardized interview and examination. Crude and age-adjusted mean serum IL-6 levels were significantly lower in postmenopausal women with than without hormone replacement therapy at baseline. Among nonusers of hormone replacement therapy, serum IL-6 concentrations were highly predictive of femoral bone loss, independently of potential confounders and plasma sex hormones. Statistical interaction between serum IL-6 and menopausal age or menopausal age group (>10 vs. 10 yr) indicated that the effect of IL-6 on bone loss weakened with increasing distance from menopause and was no longer significant in women more than 10 yr after menopause. Among women up to 10 yr past menopause (n = 39), serum IL-6 was the single most important predictor of femoral bone loss, accounting for up to 34% of the total variability of change in BMD. The unadjusted linear model predicted an annual 1.34% (95% confidence interval, 0.67–2.01) decrease in total hip BMD per log unit increase in serum IL-6. A similar, although nonsignificant, effect of serum IL-6 on vertebral bone loss was restricted to women within the first 6 yr after menopause (n = 18). These epidemiological data show that serum IL-6 is a predictor of postmenopausal bone loss, and that the effect appears to be most relevant through the first postmenopausal decade. Whether these findings reflect pathogenetic differences between early and postmenopausal bone loss, and whether serum IL-6 also predicts fracture risk need further elucidation.

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