Although the awareness of morbidity and costs related to osteoporotic fractures is increased, a real progress can be achieved only through early detection of osteoporosis before any fragility fractures occur. Dual Energy X-ray Absorptiometry (DEXA) is commonly used for diagnosis of osteoporosis by measuring bone mineral density (BMD), but it has its technical and biological limitations. Moreover, DEXA scanning only assesses mineral content in bones, which is only one component of bone strength, BMD cannot define other biological factors which contribute to fracture risk. In general, all “densitometric" techniques have high specificity but low sensitivity. The biology of bone turnover can be assessed by bone turnover markers (BTMs). They are metabolic indicators released into serum and their quantity reflects the exact metabolic activity of bones, also carry the advantages of being sensitive and specific assays. Markers of bone remodeling predominantly resorption markers have been shown to predict fracture risk independent from BMD. Osteopontin (OPN) is a non-collagenous bone matrix protein marker, it is a key regulator of many metabolic and inflammatory diseases. Studies have shown that OPN is implicated in bone metabolism and bone resorption in the remodeling process and contributing to the pathogenesis of osteoporosis. Published studies suggested that, high serum OPN level may predict the risk of sustaining osteoporotic fractures in postmenopausal women (PMW) independent of BMD. The aim of the present review is to integrate the relationship between OPN and BMD in PMW and to discuss the role of OPN as an early diagnostic factor for osteoporosis.