BONE AND CARTILAGE BIOLOGY: REMODELLING PATHWAYS, MOLECULAR PATHOGENESIS OF OSTEOPOROSIS AND OSTEOARTHRITIS, AND EVIDENCE-BASED THERAPEUTIC STRATEGIES

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背景：骨骼与软骨是特化的结缔组织，可提供骨骼支撑、实现运动功能，并保护重要脏器。二者的进行性病理退变——影响全球5亿人群的骨质疏松症（osteoporosis，伴随骨折风险的全身性骨丢失），以及影响5.95亿人群的骨关节炎（OA，关节软骨退变）——已成为全球范围内最主要的肌肉骨骼疾病负担。两种疾病共享多种共同的分子驱动机制，包括RANK/RANKL/OPG轴失调、Wnt/β-catenin通路抑制，以及促炎细胞因子介导的细胞外基质破坏。 研究目的：本研究旨在开展一项基于循证证据的简明综述，内容涵盖骨重塑生理学、关节软骨结构与稳态、骨质疏松症与骨关节炎的分子发病机制，以及针对两种疾病的循证药物与再生治疗方案。 研究方法：本研究对1995年至2024年间发表的8项一手研究资料进行系统综述，纳入研究类型包括原创分子研究、标志性随机对照临床试验、荟萃分析以及临床指南。 研究结果：RANK/RANKL/OPG轴调控破骨细胞分化；地诺单抗（anti-RANKL）靶向该轴可使椎体骨折风险降低68%（FREEDOM试验）。Wnt/β-catenin信号通路驱动成骨细胞分化；抗硬化素治疗（罗莫单抗，romosozumab）可实现获批药物中最高的骨密度增幅（腰椎骨密度升高13%）。骨关节炎的软骨退变由白细胞介素1β（IL-1β）与肿瘤坏死因子α（TNF-α）介导，二者可激活基质金属蛋白酶13（MMP-13）与解聚蛋白样金属蛋白酶5（ADAMTS-5），进而降解Ⅱ型胶原与聚集蛋白聚糖（aggrecan）。全关节置换术仍是终末期骨关节炎最有效的干预手段，可使WOMAC评分降低70%~80%。 研究结论：骨质疏松症与骨关节炎存在可靶向干预的重叠分子通路。针对高风险骨质疏松症患者，采用先合成代谢后抗吸收的治疗策略（罗莫单抗→双膦酸盐或地诺单抗）可最大化长期骨折预防效果。针对骨关节炎的新兴间充质干细胞（mesenchymal stem cell）治疗与生物制剂疗法代表了下一代治疗前沿，而全关节置换术仍是终末期疾病的确定性干预手段。