Through bone formation and resorption, which are mediated by bone cells, osteoblasts, and osteoclasts, the dynamic processes of bone creation preserve bone integrity. These bone cells' activities are normally balanced, and bone is an active tissue that constantly remodels. Reduced bone mineral density (BMD), which is clinically graded as osteopenia (ON) or the more severe condition, osteoporosis, can be caused by abnormalities in osteoblast development and mineralization activities as well as increased osteoclast activity (OP).

Low bone mineral density (LBMD) and reduced bone microarchitecture, which enhance bone fragility and raise the risk of fractures, are the key features of OP, a chronic, progressive metabolic bone disease. Age, gender, oestrogen and calcium deficiency, reduced physical activity, chronic metabolic diseases like type 2 diabetes mellitus (T2DM) and hyperthyroidism, and medications like glucocorticoids have all been shown to affect the process of bone remodelling and are consequently related to the risk of developing OP. OP is very common, especially in postmenopausal women and those from wealthy nations. For instance, the Saudi population's rate of OP prevalence is highest among older persons.

Identification of circulating proteins and their biological functions in controlling bone metabolism have recently become the subject of an expanding body of research. Our earlier research demonstrated significant variations in circulating metabolites between ON and OP patients in this regard. Several BMD-associated proteins have been discovered using multi-omics methods while analysing the human proteomes in various populations. Additionally, a number of proteomics studies have shown a connection between the progression of OP and the proteome-based indicators for bone metabolism. The precise understanding of the biological mechanisms underlying LBMD is incomplete, and the current bone-associated biomarkers are insufficient predictors of bone diseases. Nevertheless, the identification of the proteins and metabolic pathways involved in regulating bone metabolism in various populations has increased.