From bone homeostasis to skeletal metastasis and osteosarcoma: Insights into osteoclast and osteoblast roles in bone remodelling and cancer.

Bone is a highly dynamic tissue undergoing continuous remodelling through the coordinated actions of osteocytes, osteoblasts and osteoclasts. This process is tightly regulated by key signalling pathways, including the RANK/RANKL/Osteoprotegerin system, which governs bone resorption and formation. In addition, the CXCL12/CXCR4 axis and G-protein-coupled receptor 4 (GPCR4) play crucial roles in bone development, remodelling, and pathological conditions such as cancer progression. Skeletal metastases arise from complex interactions between tumour cells and the bone microenvironment, facilitating arrest, extravasation, and colonisation at secondary sites. In osteosarcoma and metastatic cancers, these molecular mechanisms contribute to tumour growth, bone degradation, bone formation and disease progression. This review highlights the intricate crosstalk between bone remodelling pathways and tumour cell invasion, providing insights into potential therapeutic targets for osteosarcoma and bone metastases.