Cytokine production and bone mineral density at the lumbar spine and femoral neck in premenopausal women

Abstract

Cytokines such as interleukin-1 (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha) can influence both bone resorption and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined. Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County, Pennsylvania were used. They included 50 healthy premenopausal women, aged 45-52 years, who had regular menses within the past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production of IL-1beta, IL-6, and TNF-alpha by PBMC was measured at the annual exam. The median values for stimulated cytokine production by PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1beta, IL-6, and TNF-alpha, respectively. There were modest correlations between cytokine production and cross-sectional BMD, ranging from r = -0.30 to r = -0.13. Trends of greater spinal bone loss were observed in women with "high" (>/=75th percentile) cytokine production of stimulated IL-1beta and IL-6 (IL-1beta: "high" = -1.56% +/- 0.70 versus "low" (<75th percentile) = -0.56% +/- 0.35, P = 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1beta and IL-6 (IL-1beta: high = 3.39% +/- 1.16 versus low = -0. 85 +/- 0.58, P = 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical bone at these sites.