INCREASED BONE-RESORBING ACTIVITY OF PERIPHERAL MONOCYTE CULTURE SUPERNATANTS IN ELDERLY WOMEN

Accelerated bone loss occurs in the years after menopause, and is an o ngoing phenomenon in elderly women. The role of cytokines in bone loss after estrogen deficiency has been shown in ovariectomized rat and mi ce models. In humans, the involvement of bone resorbing cytokines is n ow well. established. In the early years after menopause, monocyte act ivation leads to increased cytokine production. We have previously sho wn that the bone resorbing activity (BRA) of peripheral blood monocyte culture supernatants from postmenopausal women is higher than in prem enopausal (Pre-M) women. This increased activity was related to interl eukin (IL)-1, IL-6, and tumor necrosis factor-alpha levels. We here in vestigate whether monocyte activation still occurs in older women and whether this relates to bone resorption. We studied 19 healthy Pre-M, and 24 early (E-Post-M, menopause <10 yr) and 24 late CL-Post-M, menop ause >10 yr) postmenopausal women. Peripheral blood monocytes were cul tured for 48 h with 20% autologous plasma. BRA of monocyte supernatant s (expressed as theratio of monocyte supernatant over control bones su pernatant) was assessed using fetal long-bone resorbing assays. Bone r esorption was determined by urinary total pyridinoline excretion. BRA was significantly increased in E-Post-M and L-Post-M, compared with Pr e-nil subjects (1.20 +/- 0.10 and 1.15 +/- 0.20 vs. 0.73 +/- 0.10, res pectively, both P < 0.05). Moreover, BRA of bones cultured with the su pernatant of Pre-M was lower than BRA. of control bones. BRA was signi ficantly correlated with levels of IL-1, IL-6, and tumor necrosis fact or-alpha in supernatant. Supernatant IL-1 levels were increased in E-P ost-M, compared with Pre-M women (506 +/- 180 vs. 122 +/- 30, P < 0.05 ). Similarly, pyridinoline levels were increased in E-Post-M and L-Pos t-M, compared with Pre-M subjects (8.8 +/- 1 and 10.5 +/- 0.9 vs. 5.8 +/- 0.5, respectively, both P < 0.05). BRA was significantly correlate d to pyridinoline levels. These data indicate the presence of monocyte activation in L-Post-M, which may be responsible for the increased bo ne resorption and bone loss observed in this elderly population.