Osteoporosis is a metabolic skeletal disorder characterized by reduced bone mineral density and increased susceptibility to fractures. Osteopontin (OPN) is a multifunctional glycoprotein involved in bone remodelling through regulation of osteoblast and osteoclast activity. This study aimed to evaluate serum OPN levels in women with osteoporosis and investigate its association with diabetic status and metabolic parameters. This case-control study included 100 women aged 40 years and older, classified according to menopausal status (premenopausal and postmenopausal), type 2 diabetes mellitus status, and healthy controls. Serum OPN, fasting blood glucose, fasting insulin, HbA1c, and HOMA-IR were measured and compared among groups. The results demonstrated significantly elevated serum OPN levels in all osteoporotic groups compared with controls (p < 0.01), indicating increased bone remodelling activity. HbA1c and fasting blood glucose levels were also significantly higher in patient groups, whereas fasting insulin showed no significant differences. HOMA-IR was increased in some patient subgroups, particularly among older participants, but differences were not consistent across all categories. No significant correlations were observed between OPN and glycemic parameters, suggesting that OPN elevation is primarily associated with bone metabolism rather than glucose regulation. Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance of OPN for identifying osteoporosis, with an area under the curve (AUC) of 0.985, sensitivity of 91%, specificity of 100%, and accuracy of 92%. These findings indicate that serum OPN may represent a promising biomarker for osteoporosis detection and reflect alterations in bone remodelling independent of metabolic status. Further studies with larger populations and longitudinal designs are required to confirm its clinical applicability.