PMID- 8263153 OWN - NLM STAT- MEDLINE DCOM- 19940124 LR - 20041117 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 77 IP - 6 DP - 1993 Dec TI - Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines. PG - 1648-53 AB - Increased bone resorption is a mechanism contributing to bone loss in the postmenopausal period. Cytokines are involved in osteoclastic differentiation and, therefore, may play a role in the regulation of bone resorption. Several previous works showed the implication of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the modulation of bone remodeling. This study determines the concomitant production of the three cytokines and tests the bone-resorbing activity of peripheral monocyte supernatants. Four groups of women were studied: premenopausal women (n = 13; mean age, 47 +/- 0.9 yr), untreated postmenopausal women (n = 21; mean age, 52 +/- 0.6 yr), postmenopausal women treated with estrogens (n = 14; mean age, 54.2 +/- 1.1 yr), or postmenopausal women treated with ethanehydroxydiphosphonate (n = 12; mean age, 53.2 +/- 2 yr). Assignment to clinical groups was verified by plasma FSH and estradiol determinations. Lumbar spine bone mineral density was significantly higher in the premenopausal women group than in the three postmenopausal groups. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma, and after stimulation with lipopolysaccharides. IL-1, IL-6, and TNF alpha levels were measured by RIA in the monocyte surpernatants. The three cytokines were highly correlated to each other, IL-1 with IL-6 (r = 0.76; P < 0.001), IL-1 with TNF alpha (r = 0.89; P < 0.001), and IL-6 with TNF alpha (r = 0.89; P < 0.001). The mean levels of the three cytokines could not be compared because of the variations in the values. However, a trend toward lower levels in the three cytokines was noted in estrogen-treated women compared to the untreated postmenopausals. The bone-resorbing activity of monocyte supernatants, assessed by fetal long bone-resorbing assay, increased in untreated postmenopausal compared to that in premenopausal women (1.22 +/- 0.08 vs. 0.87 +/- 0.11; P < 0.05). In estrogen-treated patients, this activity decreased to premenopausal levels (0.89 +/- 0.04 vs. 0.87 +/- 0.11; P = NS). The resorbing activity was correlated to IL-1 (r = 0.28; P = 0.03), IL-6 (r = 0.52; P < 0.01), and TNF alpha (r = 0.48; P < 0.01). The addition of cytokine inhibitors and IL-1 receptor antagonist and TNF alpha antibodies to the supernatant bone culture medium induced a significant decrease in the calcium release. Those data show the involvement of several cytokines in the bone resorption process after estrogen deficiency. FAU - Cohen-Solal, M E AU - Cohen-Solal ME AD - INSERM U-349, Centre Viggo Petersen, Lariboisiere Hospital, Paris, France. FAU - Graulet, A M AU - Graulet AM FAU - Denne, M A AU - Denne MA FAU - Gueris, J AU - Gueris J FAU - Baylink, D AU - Baylink D FAU - de Vernejoul, M C AU - de Vernejoul MC LA - eng PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - *Bone Resorption MH - Cells, Cultured MH - Cytokines/*physiology MH - Female MH - Humans MH - Interleukin-1/physiology MH - Interleukin-6/physiology MH - Menopause/*blood MH - Middle Aged MH - Monocytes/*physiology MH - Tumor Necrosis Factor-alpha/physiology EDAT- 1993/12/01 00:00 MHDA- 1993/12/01 00:01 CRDT- 1993/12/01 00:00 PHST- 1993/12/01 00:00 [pubmed] PHST- 1993/12/01 00:01 [medline] PHST- 1993/12/01 00:00 [entrez] AID - 10.1210/jcem.77.6.8263153 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 1993 Dec;77(6):1648-53. doi: 10.1210/jcem.77.6.8263153.