Effects of a 21-Day Individual Rehabilitation Exercise Training Program on CRP, Cholesterol, aHSG, GDF-15, and IGF-1 Levels in Patients After Hip or Knee Replacement Surgery

Background/Objectives: Osteoarthritis (OA) is the most prevalent degenerative joint disease and a major cause of disability. In advanced stages, joint arthroplasty remains the primary treatment, yet postoperative rehabilitation plays a key role in recovery and systemic metabolic regulation. This study investigated the molecular effects of a 21-day individualized rehabilitation program in 42 patients (26 males and 16 females) following hip or knee arthroplasty. Methods: Functional capacity was evaluated by the six-minute walk test (6MWT), and serum biomarkers, including C-reactive protein (CRP), total cholesterol, α2-Heremans-Schmid glycoprotein (aHSG/fetuin-A), growth differentiation factor-15 (GDF-15), and insulin-like growth factor-1 (IGF-1), were analyzed before and after rehabilitation. Results: Unadjusted paired analyses showed a significant increase in 6MWT distance (72.2 ± 30.6 m; p < 0.001), together with reductions in body mass and BMI. Significant pre–post differences were also observed for all analyzed biomarkers, comprising decreases in CRP, total cholesterol, aHSG/fetuin-A, and GDF-15 and an increase in IGF-1 (all p < 0.001). In the additional multivariable repeated-measures models adjusted for age, sex, baseline BMI, and time since surgery, the independent main effect of time did not reach statistical significance for any of the principal outcomes (all p > 0.05; lowest p = 0.100 for 6MWT). Conclusions: Significant unadjusted within-participant differences in functional performance and circulating inflammatory and metabolic biomarkers were observed over the 21-day rehabilitation period. However, the adjusted models did not provide sufficient statistical evidence that these differences represented an independent main effect of time. Given the limited sample size and the absence of a concurrent control group, the findings should be interpreted as temporal pre–post associations rather than as evidence of an independent causal effect of rehabilitation.