Abstract: Objective  To Identify alternative indicators related to the risk of osteoporosis fractures in postmenopausal women through metabolomics and attempting to determine the predictive value of candidate metabolites.Methods From December 2018 to August 2021,158 postmenopausal women with non-traumatic hip fracture (fracture group) were enrolled in our hospital,and 197 postmenopausal women without fracture (non-fracture group) were enrolled.Quantitative analysis of serum metabolites was performed using AbsoluteIDQTM p180 kit and targeted metabolomics approach.Univariate and Multivariate Logistic regression were used to analyze the influencing factors of osteoporotic fracture in postmenopausal women,and Spearman and Pearson analysis were used to analyze their correlation.Results Compared with the non-fracture group, Only serum arginine [(105.2±22.4) μmol/L vs. (96.3±23.5)μmol/L], leucine[(180.9±50.0) μmol/L vs. (156.7±39.5) μmol/L) and spermine [(1.03±0.67)μmol/L vs. (0.51±0.12)μmol/L] were significantly increased in the fracture group (P<0.05).Logistic regression analysis showed that only serum spermidine concentration was significantly associated with hip fracture risk after adjustment for age,BMI,complications,and smoking status (HR=1.35,95%CI=1.03 to 1.65，P=0.020).According the receiver operating characteristic,serum spermidine level predicted hip fracture in postmenopausal women with an area under the curve of 0.882(95%CI:0.847 to 0.916).Spearman analysis showed that T value of hip was negatively correlated with serum spermidine level (r=-0.192,P＜0.001).The levels of serum spermine and putrescine in patients of low spermine level group were increased than those in high spermine level group.Pearson correlation analysis showed that serum spermidine level was negatively correlated with spermidine (r=-0.237,P<0.001) and putrescine (r=-0.189,P=0.004) in fracture group.Univariate and multivariate Logistic regression analysis showed that serum spermidine≥0.58 μmol/L was an independent risk factor for an increased risk of fragility hip fracture in postmenopausal women (P<0.001).Conclusion Elevated baseline serum spermidine level are associated with increased risk of hip fracture in postmenopausal women and may be useful in predicting fragility fracture in postmenopausal women.

Key words: postmenopausal, hip fracture, spermidine；fracture risk assessment, prediction