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Increased Bone Resorbing Activity of Peripheral Monocyte Culture Supernatants in Elderly Women

INSERM U 349 (M.E.C-S., M.A.D., M.C.deV.), Centre Viggo Petersen, Laboratoire de Biologie Endocrinienne (O.B-P., A.M.G.), Hopital Lariboisière, 75010 Paris; and Department of Hormonology (F.B., M.B.), Hopital Sud, Amiens, France

Address all correspondence and requests for reprints to: Dr. M. Cohen-Solal, INSERM U349, Centre Viggo Petersen, Hopital Lariboisière, 6 Rue Guy Patin, 75010 Paris, France.

Accelerated bone loss occurs in the years after menopause, and is an ongoing phenomenon in elderly women. The role of cytokines in bone loss after estrogen deficiency has been shown in ovariectomized rat and mice models. In humans, the involvement of bone resorbing cytokines is now well established. In the early years after menopause, monocyte activation leads to increased cytokine production. We have previously shown that the bone resorbing activity (BRA) of peripheral blood monocyte culture supernatants from postmenopausal women is higher than in premenopausal (Pre-M) women. This increased activity was related to interleukin (IL)-1, IL-6, and tumor necrosis factor- levels. We here investigate 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 (L-Post-M, menopause >10 yr) postmenopausal women. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma. BRA of monocyte supernatants (expressed as the ratio of monocyte supernatant over control bones supernatant) was assessed using fetal long-bone resorbing assays. Bone resorption was determined by urinary total pyridinoline excretion. BRA was significantly increased in E-Post-M and L-Post-M, compared with Pre-M subjects (1.20 ± 0.10 and 1.15 ± 0.20 vs. 0.73 ± 0.10, respectively, both P < 0.05). Moreover, BRA of bones cultured with the supernatant of Pre-M was lower than BRA of control bones. BRA was significantly correlated with levels of IL-1, IL-6, and tumor necrosis factor- in supernatant. Supernatant IL-1 levels were increased in E-Post-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-Post-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 correlated to pyridinoline levels. These data indicate the presence of monocyte activation in L-Post-M, which may be responsible for the increased bone resorption and bone loss observed in this elderly population.

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