The role of circulatory proteomics in
osteoporosis is unclear.
Proteome-wide profiling holds the potential to offer mechanistic insights into
osteoporosis. Serum
proteome with 413
proteins was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, and the 2nd, and 3rd follow-ups (7704 person-tests) in the prospective Chinese cohorts with 9.8 follow-up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at follow-ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the
osteoporosis (OP)-related proteomic features. The relationships between
serum proteins and BMD in the two cohorts were estimated by linear mixed-effects model (LMM). Meta-analysis was then performed to explore the combined associations. We identified 53
proteins associated with
osteoporosis using LightGBM, and a meta-analysis showed that 22 of these
proteins illuminated a significant correlation with BMD (p < 0.05). The most common
proteins among them were PHLD,
SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified
proteins were used to generate the biological age (BA) of bone. Each 1 SD-year increase in KDM-Proage was associated with higher risk of LS-OP (hazard ratio [HR], 1.25; 95% CI, 1.14-1.36, p = 4.96 × 10-06 ), and FN-OP (HR, 1.13; 95% CI, 1.02-1.23, p = 9.71 × 10-03 ). The findings uncovered that the
apolipoproteins, zymoproteins, complements, and
binding proteins presented new mechanistic insights into
osteoporosis. Serum proteomics could be a crucial
indicator for evaluating bone aging.