BONE AND CARTILAGE BIOLOGY: REMODELLING PATHWAYS, MOLECULAR PATHOGENESIS OF OSTEOPOROSIS AND OSTEOARTHRITIS, AND EVIDENCE-BASED THERAPEUTIC STRATEGIES
Abstract
Background: Bone and cartilage are specialized connective tissues that provide skeletal support, enable locomotion, and protect vital organs. Their progressive pathological deterioration—osteoporosis (systemic bone loss with fracture risk) affecting 500 million people globally and osteoarthritis (OA, articular cartilage degradation) affecting 595 million—constitutes the most prevalent musculoskeletal disease burden worldwide. Both conditions share common molecular drivers including RANK/RANKL/OPG axis dysregulation, Wnt/β-catenin pathway suppression, and pro-inflammatory cytokine-mediated extracellular matrix destruction.
Objective: To provide a concise, evidence-based review of bone remodelling physiology, articular cartilage structure and homeostasis, the molecular pathogenesis of osteoporosis and osteoarthritis, and evidence-based pharmacological and regenerative therapies for both conditions.
Methods: A systematic review of eight primary sources—original molecular studies, landmark randomized clinical trials, meta-analyses, and clinical guidelines published between 1995 and 2024—was conducted.
Results: The RANK/RANKL/OPG axis governs osteoclast differentiation; its therapeutic targeting by denosumab (anti-RANKL) reduces vertebral fracture risk by 68% (FREEDOM trial). Wnt/β-catenin signalling drives osteoblast differentiation; anti-sclerostin therapy (romosozumab) achieves the highest bone mineral density gains (+13% lumbar spine) of any approved agent. OA cartilage loss is driven by IL-1β and TNF-α activating MMP-13 and ADAMTS-5, degrading type II collagen and aggrecan. Total joint arthroplasty remains the most effective intervention for end-stage OA (WOMAC reduction 70–80%).
Conclusion: Osteoporosis and osteoarthritis share overlapping molecular pathways amenable to targeted therapy. Sequential anabolic-then-antiresorptive strategy for high-risk osteoporosis (romosozumab → bisphosphonate or denosumab) maximizes long-term fracture prevention. Emerging mesenchymal stem cell and biologic therapies for OA represent the next therapeutic frontier, while total joint arthroplasty remains the definitive intervention for end-stage disease.
Keywords
bone remodelling, osteoporosis, osteoarthritis, RANK/RANKL/OPG, osteoclast, osteoblast, Wnt/β-catenin, sclerostin, bisphosphonates, denosumab, romosozumab, MMP-13, ADAMTS-5, articular cartilage, total joint arthroplasty, mesenchymal stem cells
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