BACKGROUND: Metabolic syndrome (MetS) is a collection of clinical conditions, including central obesity, hypertension, glucose intolerance and dyslipidemia. The long-term inflammatory and metabolic dysfunction associated with MetS may contribute to osteoarthritic processes leading up to total joint arthroplasty (TJA). The purpose of this study was to investigate levels of metabolic biomarkers and the prevalence of MetS in patients undergoing TJA. METHODS: Under IRB approval, citrated plasma samples were collected from 41 patients undergoing total hip and knee arthroplasty (THA/TKA) preoperatively and day 1 postoperatively. Control group consisted of 25 healthy human plasma samples (female and male, 18-35 years old) purchased from George King Biomedical Inc. (Overland Park, KS, USA). Samples were profiled for c-peptide, ferritin, IL-6, insulin, resistin, TNF-alpha, IL-la, leptin, and PAI-1 using metabolic biochips purchased from RANDOX Co. (Antrim, Northern Ireland). NCEP/ATP III guidelines were used to evaluate which patients met MetS criteria. RESULTS. Levels of IL-6, resistin, TNF-a, IL-la, leptin, and PAI-I were significantly elevated in patients uridergoing TJA compared to normal. C-peptide and insulin were both decreased in TJA compared to normal. No significance was found when comparing TJA to normal for ferritin. TNF alpha was significantly lower in TJA+MetS compared to TJA-MetS, while other biomarkers showed no diffbrence in TJA MetS populations. Insulin & c-peptide both showed a significant decrease in TJA-MetS compared to normal, but levels in TJA+MetS patients were not significantly different from controls. Resistin showed significant increases in TJA+MetS vs. normal, but not in TJA-MetS vs. normal. CONCLUSIONS: Overall, the differing metabolic profile seen in patients undergoing TJA suggest ongoing metabolic dysfunction. Insulin and c-peptide patterns among the different test groups hint toward a complex and dysfunctional metabolic process involved, with leptin and underlying insulin resistance playing a role. Increased resistin in TJA+MetS, but not in TJA-MetS, compared to normal, suggests that while elevated resistin levels may be associated with the osteoarthritic process, levels are further attenuated by MetS, which is highly prevalent in this population. Increased TNFa in TJA-MetS compared to TJA+MetS may be an artifact of differing sample populations or a true complication of the complex pathophysiology and medical regimen seen in patients with both OA and MetS. The lack of difference seen in the remaining biomarkers suggest that having MetS as a comorbidity does not contribute to the elevated levels seen in patients undergoing TJA.