Osteoarthritis as a Whole-Joint Disease, Part I: Current Standard of Care and Structural Therapeutic Targets in Cartilage, Synovium, and Subchondral Bone.

This first part of the review provides the foundation for the 2 part series by examining current standard-of-care management and therapeutic targets within the joint compartment, including cartilage, synovium, and subchondral bone. It focuses on structural and mechanism-informed strategies directed at cartilage metabolism, synovitis and inflammation, and subchondral bone remodeling, while highlighting the persistent gap between biological plausibility, structural signals, and consistent clinical benefit. Together with Part II, which addresses nociceptive, systemic metabolic, senescence-associated, and regenerative therapeutic strategies, this review frames osteoarthritis as a heterogeneous whole-joint disorder that will likely require more phenotype-informed trial design and improved end points.