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ROS are involved in critical biological functions such as signal transduction; when the production of ROS is imbalanced, excessive ROS causes oxidative stress, and subsequent cellular damage. Oxidative stress is linked to numerous pathological disorders in major organs including the skeletal system. In an aging society, understanding the role of ROS in skeletal health is critical to developing preventative and therapeutic interventions. Oxidative stress causes defects in cellular differentiation, apoptosis, mitochondrial dysfunction, and inflammation. The effects of oxidative stress on the skeletal system have been implicated in the development of osteoporosis, knee osteoarthritis, and osteonecrosis by inhibiting bone remodeling, increasing osteoclast activity, and decreasing osteoblast function. ROS are also involved in many signaling pathways that regulate immune defense, cell proliferation, and inflammation. This underscores the importance of maintaining a balance between ROS and antioxidants to prevent oxidative stress and related diseases. Targeting ROS and oxidative stress mechanisms may offer new treatments for diseases affecting the skeletal system and other organs, potentially improving health outcomes, and extending healthy lifespans. This review highlights the significant impact of oxidative stress on skeletal health and explores potential preventative and therapeutic strategies to mitigate the adverse effects of ROS.<\/jats:p>","DOI":"10.1002\/jor.26075","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T21:50:02Z","timestamp":1743285002000},"page":"1059-1072","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Pathophysiology of the Effects of Oxidative Stress on the Skeletal System"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4122-7119","authenticated-orcid":false,"given":"Issei","family":"Shinohara","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University School of Medicine Stanford California USA"},{"name":"Department of Orthopaedic Surgery Kobe University Graduate School of Medicine Kobe 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