Xylosyltransferase-I serum activity is a promising biomarker for postmenopausal osteoporosis.

Osteoporosis is characterized by reduced bone mineral density (BMD) and impaired bone microarchitecture, leading to increased fracture risk. Current bone turnover biomarkers reflect osteoclast and osteoblast activity but do not capture the status of bone extracellular matrix (ECM). Human xylosyltransferase (XT), which initiates glycosaminoglycan biosynthesis, is essential for ECM integrity and was recently implicated in skeletal disorders. To investigate its role in osteoporosis, serum activity of the two XT isoenzymes, XT-I and XT-II, were quantified in 40 postmenopausal women with osteoporosis and 40 age-matched healthy controls using a SPE-UPLC-MS/MS assay. Associations with BMD, fracture risk scores (FRAX) and markers of bone turnover were assessed using Pearson correlation analysis and principal component analysis (PCA). Serum XT-I activity was significantly reduced in postmenopausal osteoporosis patients, whereas XT-II activity remained unchanged. XT-I showed strong positive correlations with all BMD parameters and significant negative correlations with FRAX and bone turnover markers. PCA positioned XT-I activity alongside BMD parameters on the primary axis of disease-related variance, opposing bone resorption markers and fracture risk scores. These findings identify XT-I as a promising biomarker reflecting ECM remodeling in postmenopausal osteoporosis and support further investigation of its role in bone remodeling.