Background/Objectives: Knee osteoarthritis (OA) is increasingly recognized as a condition with an inflammatory component. Elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are associated with disease severity. However, the effects of physical therapy on inflammatory biomarkers remain unclear. This review aimed to evaluate the effects of physical therapy interventions on CRP and ESR in adults with knee OA. Methods: Following PRISMA 2020 guidelines, PROSPERO (CRD42024590843), PubMed, MEDLINE, Embase, Scopus, Web of Science, and Google Scholar were searched from inception to 3 November 2024. Randomized controlled trials comparing any physical therapy intervention with a control condition were included. Risk of bias was assessed using the Physiotherapy Evidence Database (PEDro) scale, and certainty of evidence was evaluated using the GRADE approach. Random-effects meta-analyses were performed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Seven RCTs (n = 523 participants) were included. Pooled analysis showed a statistically significant reduction in CRP (SMD = −1.05; 95% CI: −1.80 to −0.31; p = 0.006); however, substantial heterogeneity was observed (I² = 93%), limiting confidence in the pooled estimate. Certainty of evidence for CRP was rated as moderate. No significant effect was observed for ESR (SMD = −0.20; 95% CI: −0.84 to 0.45; p = 0.56; I² = 63%), with low certainty. Conclusions: Physical therapy may reduce CRP levels in knee OA; however, substantial heterogeneity limits confidence in the precision and generalizability of this effect. These findings should be interpreted cautiously and considered exploratory. Further well-designed RCTs are required.

Background and Objectives: Low-grade systemic inflammation plays an important role in the pathophysiology of knee osteoarthritis (OA), yet the effects of joint mobilization on inflammatory biomarkers remain unclear. This randomized clinical trial investigated the effects of mobilization with movement (MWM) compared with sham MWM on inflammatory biomarkers and clinical outcomes in individuals with knee OA. Materials and Methods: Forty participants with mild-to-moderate knee OA were randomly assigned to either a mobilization group receiving standardized care plus MWM (n = 20) or a sham mobilization group receiving standardized care plus sham MWM (n = 20). Interventions were delivered twice weekly for four weeks. Primary outcomes were inflammatory biomarkers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Secondary outcomes included pain intensity (Visual Analog Scale [VAS]), physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), knee range of motion (ROM), and muscle strength. Outcomes were assessed at baseline and after the 4-week intervention. This study was prospectively registered at ClinicalTrials.gov (NCT07166068) on 28 November 2024. Results: Both groups demonstrated significant improvements in one inflammatory biomarker, namely CRP, and all secondary outcomes following treatment (all p < 0.05). However, no significant between-group differences were observed for CRP, ESR, pain, function, or muscle strength (all p ≥ 0.256). Participants in the MWM group showed greater improvement in knee flexion ROM compared with the sham MWM group (adjusted mean difference = 6.56°, 95% CI: 0.14–13.00, p = 0.046), with a moderate effect size. Conclusions: MWM combined with standardized care did not produce superior improvements in inflammatory biomarkers or most clinical outcomes compared with sham MWM over four weeks.