Relationship of Cytokines to Bone Mineral Density and Content in Postmenopausal Women

Abstract

Loss of estrogen results in a decrease in bone mineral density (BMD) and content (BMC) and an increase in cytokine production. Elevated cytokines lead to an upregulation of osteoclastogenesis. We determined the relationship between cytokines and BMD and BMC in healthy, postmenopausal women (n=105) not on hormone therapy. Spine BMD and BMC (SpBMD, SpBMC) and hip BMD and BMC were measured by dual energy x-ray absorptiomety. We stimulated whole blood with three concentrations of lipopolysaccharide (low [L], medium [M], high [H]) and assessed cytokine production by a human cytokine multiplex immunoassay (LINCO research). Cytokine data were transformed. We observed significant associations between SpBMD and interleukin (IL)-1M (p<0.05) and IL-1H (p<0.01) plus SpBMC and IL-1M (p=0.01), granulocyte-colony stimulating factor (G-CSF)M, IL-6M, and IL-1H (p<0.05). Femoral neck (FN) BMC was significantly related to IL-1M, interferon gamma (INFγ)M, IL-7H, IL-8H, and IL-1H (p<0.05) while total hip (TH) BMD was significantly associated with IL-1M (p<0.05). Stepwise multiple regression models were: SpBMD=0.651 + 0.00007(IL-1H) + 0.005(age) SpBMC=32.869 - 1.982(BMI) + 0.633(WT) + 0.459(age) + 0.377(IL-1M) FN BMC=0.637 + 0.029(HT) + 0.0001(IL-1H) - 0.509(IL-8H) + 0.212(IL-7H) TH BMD=0.728 + 0.002(WT) + 0.003(IL-1M) We confirmed that cytokine concentrations were related to SpBMC, SpBMD, FN BMC and TH BMD, but not to BMD or BMC at other sites, suggesting that cytokines mainly affect trabecular bone. Supported by funds from NIAMS/NIH (AR046922) and USDA/ARS,WHNRC.