Yali Wen,1,* Shoujun Cheng,2,* Liming Gou,3,* Weihong Zhou,4,* Yishan Li,5 Ruoxuan Wang,6 Ji Wu,7 Xuening Dai,8 Ming Gao,9 Lei Wang,10 Bin Xue,3,11,12 Yinhe Wang1,13 

1Department of Orthopedics, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Clinical Laboratory, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China; 3Department of Translational Medicine Research Center, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Health Management Centre, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China; 5Department of Translation Studies, Army Engineering University of PLA, Nanjing, People’s Republic of China; 6Department of Clinical Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 7Department of Orthopedics, Sir Run Run Hospital, Nanjing, Jiangsu, People’s Republic of China; 8Department of Geriatrics, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 9Department of Endocrinology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 10Department of Orthopedics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 11Department of Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 12Department of General Surgery, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 13Department of Orthopedics, Clinical College, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yinhe Wang, Department of Orthopedics, Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, 210000, People’s Republic of China, Email milkyway199@hotmail.com Bin Xue, Translational Medicine Research Center, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, People’s Republic of China, Email xuebin@njmu.edu.cn

Purpose: This study aims to identify a novel biomarker for the early detection and prevention of osteoporosis.
Methods: A cross-sectional study (n=138, from 497 screened) was conducted at Nanjing Drum Tower Hospital (Sep 2023-Jun 2024). A second multicenter validation cohort (n=165) was collected (Jun 2024-Jan2025) from three hospitals, including 90 controls, 35 osteopenia, and 40 OP cases. Serum LCAT was measured via ELISA. Statistical analyses (t-tests, ANOVA, Mann–Whitney U) compared LCAT levels across bone health groups and genders. Correlations between LCAT and biochemical parameters were assessed, and ROC analysis evaluated diagnostic performance.
Results: Serum LCAT levels were significantly lower in both the osteopenia (n=32, p< 0.01) and osteoporosis groups (n=50, p< 0.001) compared with control group (n=56). The results from this second cohort support our previous cross-sectional findings, serum LCAT levels in controls (44.41 ± 14.16), osteopenia (32.15 ± 8.93) and osteoporosis (22.15 ± 7.07). In this multicenter study, serum LCAT levels were evaluated and found to be significantly decreased in the primary osteoporosis group compared to controls across all populations with notable differences by sex (males: U=207.5, p=0.0031; females: U=520.5, p=0.0001) and age (≤ 55 years: p=0.005; > 55 years: p=0.0001). LCAT levels showed positive correlations with T/Z-scores, BMI, ALT, AST, LDL-C, and serum phosphorus, and negative correlations with age and serum creatinine. ROC analysis yielded an AUC of 0.822, with sensitivity and specificity of 75.9% and 78%, respectively. Moreover, serum LCAT levels exhibited significantly higher predictive value for osteoporosis than that of conventional serum 25-hydroxyvitamin D (25OHD) levels.
Conclusion: We demonstrate for the first time that reduced serum LCAT concentrations predict osteoporosis risk independently of confounding factors, qualifying it as a promising early-stage diagnostic biomarker. These findings establish LCAT as a demography-invariant diagnostic biomarker for early-stage osteoporosis, suggesting its potential utility in population-wide screening programs.

Keywords: osteoporosis, early detection, LCAT, hepatogenic factor, biomarker