Serum LCAT as a Gender-Neutral Biomarker for Early Osteoporosis: A Multicenter Cohort Validation Study
Yali Wen1, Shoujun Cheng2, Liming Gou3
1Department of Orthopedics, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
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.
