Knee osteoarthritis management across the joint-preservation continuum: current evidence and future directions.

Knee osteoarthritis is a leading cause of chronic pain, disability, and mobility limitation, with increasing prevalence driven by population aging, obesity, and joint injury. Although historically viewed as passive cartilage "wear and tear," knee osteoarthritis is now understood as a heterogeneous whole-joint disease involving cartilage matrix degradation, chondrocyte dysfunction, synovial inflammation, subchondral bone remodeling, genetic and epigenetic susceptibility, and altered biomechanics. This narrative review examines current and emerging strategies for knee osteoarthritis management across the joint-preservation continuum. PubMed/MEDLINE, the Cochrane Library, and Google Scholar were searched through August 2026, prioritizing systematic reviews, randomized controlled trials, clinical practice guidelines, and relevant primary studies, with selective inclusion of preclinical evidence for emerging therapies. This broader biological understanding has identified therapeutic targets and supports a joint-preservation continuum that extends from weight management, exercise, and pharmacologic symptom control to intra-articular therapies, cartilage restoration, and investigational molecular or gene-based interventions. Currently available intra-articular therapies may provide symptom relief in selected patients but have not demonstrated consistent structural disease modification, and guideline recommendations differ for several intra-articular, orthobiologic, and regenerative treatments because of substantial heterogeneity in the available evidence. Emerging approaches, including cytokine-directed therapy, photobiomodulation, platelet-rich plasma, and tissue engineering, aim to influence disease mechanisms, although their clinical maturity and evidentiary strength vary substantially. Future precision-medicine strategies may integrate clinical phenotype, biological profiles, imaging, biomarkers, and genetic risk to identify patients most likely to progress or respond to specific interventions. At present, no disease-modifying osteoarthritis drug is approved for knee osteoarthritis. Nevertheless, biologically informed, stage-appropriate care may help preserve function, address modifiable disease drivers, and extend native-joint health while maintaining the essential role of total knee arthroplasty for end-stage disease.