Changes in Cytokines, Biomarkers of Bone Turnover and Hormones Are Associated With Bone Loss in Postmenopausal Indian Women

Background: The pro-inflammatory cytokines that are associated with the decline in ovarian function during menopause are involved in the pathophysiology of postmenopausal bone loss, which has not been examined in Indian postmenopausal women. Objectives: This study assessed the extent of changes in pro-inflammatory cytokines in relation to bone turnover markers, hormones, and bone mineral density (BMD) during menopausal transition in Indian women. Materials and Methods: Levels of interleukin 1 (IL1β), interleukin 6 (IL6), and tumor necrosis factor (TNF α) ; the bone markers osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), carboxy terminal telopeptide (CTX), and deoxypyridoniline (DPD) ; and the hormones parathyroid hormone (PTH), follicle-stimulating hormone (FSH), and estrone glucuronide (E1G) were measured by enzyme linked immunosorbant assay (ELISA) in blood and urine samples of premenopausal (age: 21-40 years, n=124) and menopausal women (41-70 years, n=256) without fractures. Bone mineral density (BMD) in the femur and spine was measured by dual energy x-ray absorptiometry (DXA). Results: Of the cytokines that were measured, only IL6 increased significantly in all 3 groups of menopausal women (compared with premenopausal healthy women. The changes in IL6 paralleled changes in markers of bone resorption and correlated positive- ly with bone turnover markers and negatively with BMD and E1G levels. In menopausal women, the rise in IL6, CTX, and DPD was high ( 100%) and was associated with a decline in E1G ( 75%) and BMD levels ( 22%) during the first 5 years of menopause, indicating that bone loss is confined to the first decade of menopause. Conclusions: IL6 correlates negatively with estrogens and BMD and positively with bone resorption markers. Thus, IL6 levels, in conjunction with CTX, DPD, and estrogen levels, improve the prediction of bone loss in menopausal women.