IL-6 and Leptin Are Potential Biomarkers for Osteoporotic Fracture Risk Assessment and Prediction of Postmenopausal Women with Low Bone Mass: A Follow-Up Study Using a Regional Sample Cohort

Abstract

Osteoporotic fracture, a major complication which is known as the outcome postmenopausal osteoporosis, seriously threatens the health of postmenopausal women. At present, the traditional osteoporotic fracture prediction methods are characterized by inconvenient application and time-consuming statistical results, while predictive serum biomarkers can make up for this shortcoming. Accurate and advanced risk prediction of osteoporotic fracture is meaningful to early prevention and intervention, effectively avoiding the risk of this disease and the secondary fracture in the surgical treatment. In this study, based on the BEYOND cohort, a 2-year follow-up study was conducted after subjects participated to survey if OF occurred. Independent sample $t$ -test and Mann–Whitney $U$ -test were used to analyze the differences of bone metabolism biomarkers between the OF and non-OF group. Cox proportional hazard model was used to screen the potential biomarkers might be used to predict OF risk. ROC curves and AUCs were used to analyze the predictive accuracy, and the Delong’s test was used to compare the differences between the AUCs. 15 postmenopausal women with low bone mass and OF were found, and other 60 subjects without OF were matched with 1 : 4, age, and BMI classification as control group. The serum IL-6 ( $\text{OR}=1.139$ , $95\%\text{CI}=1.058-1.226$ ) and leptin ( $\text{OR}=0.921$ , $95\%\text{CI}=0.848-1.000$ ) were found as OF risk predictive biomarkers for postmenopausal women with low bone mass with high accuracy ( $\text{IL}-6=0.871$ ) ( $\text{leptin}=0.813$ ) and accuracy enhanced when they were combined ( $\text{AUC}=0.898$ ). The results of Delong’s test showed that the difference of AUC between leptin and IL-6&Leptin was meaningful ( $P=0.024$ ) but meaningless between IL-6 and leptin ( $P=0.436$ ), IL-6 and IL-6&Leptin ( $P=0.606$ ). To sum up, IL-6 and leptin are the predictive biomarkers of OF for postmenopausal women with low bone mass. The IL-6 can improve the prediction accuracy of leptin ( $P=0.024$ ), but not vice versa ( $P=0.606$ ). Trial Information. Registered on the Chinese Clinical Trial Registry already. (Registration Number: ChiCTR-SOC-17013090).