Oxytocin and bone status in men: analysis of the MINOS cohort.

UNLABELLED: Oxytocin, a neurohypophysial hormone, regulates bone metabolism in animal studies and postmenopausal women. In men, oxytocin is not associated with bone mineral density, bone turnover markers, or prevalent fractures, but weakly negatively with incident fragility fracture requiring further studies. INTRODUCTION: We previously showed that serum oxytocin (OT) level is associated with bone mineral density (BMD) and bone turnover rate in postmenopausal women. The aim of our study was to assess the relationship between circulating OT levels and bone status in men. METHODS: In 552 men aged 50 and older from the MINOS cohort, we measured serum levels of OT. We assessed the association of serum OT levels with BMD (lumbar, femoral neck, total hip), bone turnover markers (BTM) (serum N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (bone ALP), and C-terminal telopeptide of type I collagen (CTX-I)) and fracture risk. RESULTS: In the univariate analysis, serum OT level was not associated with BMD at any site, BTM levels, or with prevalent or incident fracture. OT was significantly correlated with body mass index (BMI) (r = 0.17, p < 0.001), total or bioavalaible 17ß-estradiol (r = 0.09, p = 0.04 and r = 0.20, p < 0.001, respectively), free testosterone (r = 0.17, p < 0.001), and leptin (r = 0.16, p < 0.001). Multivariate analysis did not show significant relationship between serum OT and BMD. After adjustment for age, BMI, interaction BMI/age, history of fall in the last year, and BMD, OT and prevalent fracture were not associated. By contrast, the same analysis with additional adjustment for prevalent fracture showed a weakly significant negative association between OT and incident fracture, e.g., after adjustment for femoral neck BMD, HR = 0.73, 95 %CI 0.55-0.99, p = 0.04. CONCLUSION: In men, serum OT levels are not associated with BMD, bone turnover rate, or prevalent fractures. The weak negative relationship with fracture risk requires further studies.

Improvement of normothermic rat liver ischemia/reperfusion by muramyl dipeptide.

Normothermic ischemia and reperfusion (I/R) of the liver remains a major problem after liver surgery and transplantation. Activation of Kupffer cells (KCs) after normothermic I/R is responsible for a massive release of various monokines such as tumor necrosis factor alpha (TNF-alpha) and a decrease in phagocytic activity. Muramyl dipeptide (MDP) is an immunostimulant that increases phagocytic activity of KCs. The aim of this study was to demonstrate that MDP pretreatment might protect the liver against I/R injury by a modification of KC functions. Rats were divided into three groups: group 1, control, Ringer's lactate administration; group 2, MDP (N-acetyl-muramyl-d-alanyl-d-isoglutamine) treatment; group 3, sham-operated control animals. MDP (500 microg/250 g) was injected intravenously 5 min before the induction of 90 min ischemia. Survival rates were compared and serum activities of TNF-alpha, aspartate aminotransferase, and alanine aminotransferase were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver and KC activity were assessed 6 and 9 h after the end of ischemia, respectively. MDP treatment significantly increased 7-day survival (86.6%) compared with nontreated rats (40%, P < 0.001). Serum activities of TNF-alpha and aminotransferases were significantly decreased after MDP treatment, whereas phagocytic capacity of KCs was partially restored. The extent of liver necrosis was decreased after MDP administration. A significant difference was observed for other histological parameters studied, except for steatosis. Our findings have demonstrated that MDP is able to protect the liver from ischemic insult by modulation of KC activity (TNF-alpha release and phagocytic capacity). Control of macrophage activity may offer a new strategy to reduce ischemic injury of the liver.