BACKGROUND: Osteomalacia is a bone metabolic disease resulting from inadequate mineralization due to vitamin D deficiency and disturbances in calcium and phosphate metabolism. To date, information on the combined assessment of traditional markers of mineral metabolism and bone turnover biomarkers in patients with osteomalacia remains scarce. Therefore, the present investigation was conducted to assess the diagnostic value of biochemical and bone turnover markers for osteomalacia and to identify the potential gender-specific differences.METHODS: This case–control study included 100 subjects with osteomalacia and 100 healthy controls. Blood samples were collected, and serum levels of calcium, phosphate, and alkaline phosphatase (ALP) were measured using chemistry analyzer; vitamin D were and parathyroid hormone (PTH) were measured using immunofluorescence; while procollagen type 1 N-propeptide (P1NP), C-terminal telopeptide (CTX) and sclerostin level were measured using enzyme linked immunosorbent assay (ELISA). The diagnostic utility of the evaluated biomarkers was then subsequently assessed.RESULTS: Serum calcium, phosphate, and vitamin D were significantly reduced, while ALP and PTH concentrations were increased in osteomalacia subjects compared to control (p<0.001). Sclerostin concentrations were significantly higher in osteomalacia subjects than controls (p<0.003), especially in females than in males (p=0.021). P1NP levels were significantly altered in osteomalacia subjects compared with controls (p<0.001). Biochemical profiles were comparable across genders, except for sclerostin, which was significantly higher in females (p=0.021) and lower T-scores compared with males. BMI increased significantly with age (p=0.024). ROC analysis showed strong discriminatory ability of evaluated biomarkers within the study population.CONCLUSION: Elevated sclerostin and P1NP levels were associated with osteomalacia and may be useful biomarkers reflecting impaired bone formation, improving diagnostic accuracy when used alongside conventional markers. Sclerostin concentrations were considerably higher in female patients than in males, suggesting possible sex-related differences in bone metabolism.KEYWORDS: sclerostin, vitamin D, osteomalacia, mineralization, bone turnover biomarkers