Estrogenic status influences nitric oxide-regulated TNF-α release from human peripheral blood monocytes

Cytokines and nitric oxide (NO) have been implicated in bone loss caused by estrogen deficiency. Here we evaluated the effect of nitric oxide synthase (NOS) inhibitors on the bone particle resorbing activity and TNF-α release of cultured peripheral blood monocytes (PBM) obtained from 10 premenopausal (PreM) and 10 postmenopausal (PostM) women. Gonadal status (menopause<3 yr) was assessed by FSH and estradiol. Bone alkaline phosphatase and N-Telopeptide were significantly increased in PostM. Significant differences between PreM and PostM women were observed in bone mineral density of lumbar spine. The bone particle resorbing activity of PBM cultured in the presence of L-arginine-methyl ester (NAME) or aminoguanidine. NOS inhibitors, was determined by 45 Ca release from rat bone labeled particles. TNF-a release was assayed in supernatants by ELISA. 45 Ca release was higher in PostM (p<0.01) and was enhanced by NAME (p<0.02). Furthermore, TNF-a release from PBM was significantly higher in PostM (p<0.01). Aminoguanidine significantly increased TNF-a release in PreM. Based on these findings and on the evidence that estrogen stimulates NOS, we suggest that estrogen withdrawal may reduce the inhibitory effect of NO on TNF-α release. Thus, this increased production of TNF-a could contribute to the increased postmenopausal bone turnover.