Introduction. Whether biochemical markers of bone metabolism can be used in assessing the conditions of implant fixation is unknown. In this study, the serum levels of three bone markers were measured prospectively in patients undergoing total knee arthroplasty (TKA) to determine if patients with different fixation conditions of the tibial component showed any differences in the levels of the markers. Materials and methods. The fixation of the tibial component in 40 knees (40 patients, 14 male and 26 female, average age 71 years) was assessed by radiostereometric analysis (RSA), and based upon the pattern of migration, implants with stable fixation (n=25) and potentially unstable fixation (n=15) were identified. Serum levels of carboxyterminal propeptide of type I procollagen (PICP), osteocalcin (OC) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were assessed and compared between the two fixation groups. Blood samples were obtained preoperatively (baseline) and repeated postoperatively at 1 week, 3, 6, 12, and 24 months. Results. The baseline levels of the markers were statistically the same (p>0.05) between the two fixation groups. Postoperatively, ICTP levels in the unstable group were significantly higher than in the stable group from 6 to 24 months (p=0.02). Levels of OC in the unstable group were higher at 12 and 24 months compared with the stable group, reaching statistical significance only at 12 months (p=0.03). No difference in the levels of PICP was found between the two groups. Conclusion. The findings indicate a more active bone turnover probably at the bone-cement/implant interface in knees with potentially unstable fixation. It reveals the potential value for biochemical markers in monitoring implant fixation and aseptic loosening and suggests a possibility for improving implant fixation by drugs which inhibit osteolysis.