Mechanism of Bone Destruction

Bone destruction is central to conditions like osteoporosis, rheumatoid arthritis, and cancers with bone metastases. It results from an imbalance between bone resorption by osteoclasts and formation by osteoblasts. Osteoclast activity is regulated by the RANK/RANKL/OPG axis, where an increased RANKL/OPG ratio promotes osteoclastogenesis. Inflammatory cytokines (e.g., TNF-?, IL-1, IL-6) enhance RANKL expression and osteoclast survival. In cancer, tumor-derived factors like PTHrP and prostaglandins further drive RANKL-mediated bone loss. Bone resorption releases growth factors such as TGF-?, fueling tumor growth and perpetuating degradation. Enzymes like MMPs and cathepsin K degrade bone matrix, while hypoxia and mechanical stress also contribute. Understanding these mechanisms supports treatments like bisphosphonates, RANKL inhibitors (e.g., denosumab), and anti-cytokine therapies, which effectively reduce bone loss.