OBJECTIVE Total joint arthroplasty (TJA) is the most effective treatment for end-stage osteoarthritis (OA). Although systemic acylcarnitine alterations have been reported in OA, long-term metabolic changes after TJA remain poorly understood. Existing metabolomic studies are cross-sectional and have not compared post-TJA changes with age- and sex-matched controls. We examined metabolic markers before and 7 years after TJA to assess long-term systemic metabolic changes relative to healthy aging controls. METHOD Fasting serum acylcarnitines were measured using liquid chromatography mass-spectrometry in a longitudinal cohort of participants with end-stage OA undergoing TJA (n = 70) and in age- and sex-matched healthy controls (n = 82) at baseline and 7-year follow-up. Acylcarnitine concentrations were compared between groups and longitudinally within participants, with analyses adjusted for age, sex, body mass index, hypertension status, and corrected for multiple comparisons. RESULTS A total of 70 patients (age 62 ± 7) with severe OA who were undergoing TJA and 82 matched controls without OA were included in the study. Forty-eight acylcarnitine measures and ratios passed quality control. Fifteen acylcarnitines changed differently between groups over follow-up; six measures differed at baseline and 12 at follow-up. Five baseline differences normalized, whereas 11 new between-group differences emerged. After adjustment for baseline metabolite concentrations, seven acylcarnitines showed differential longitudinal change: four short-chain species (C5-OH, C5-DC, C5-M-DC, C5:1-DC) and three long-chain species (C14:2-OH, C16:2, C18:1). The four short-chain species increased 19.8-32.0% more in the TJA group than in controls. Free carnitine (C0) declined relative to controls, with a 24.8% lower longitudinal change (ratio 0.75, 95% CI 0.62-0.91). Several medium- and long-chain acylcarnitines that were lower at baseline normalized toward control concentrations. Total acylcarnitine/free carnitine increased 32.3% more in the TJA group (ratio 1.32, 95% CI 1.17-1.50), with the baseline group difference resolving by follow-up. CONCLUSION TJA was associated with partial normalization of select circulating acylcarnitines; however, persistent abnormalities in hydroxy- and dicarboxy-acylcarnitines suggest ongoing alterations in lipid handling. Reduced carnitine buffering capacity and shifts toward alternative oxidation pathways further indicate incomplete restoration of systemic fatty-acid metabolism. Overall, these findings support pathway-specific metabolic remodeling rather than full metabolic normalization following TJA. REGISTERED ON WWW. CLINICALTRIALS GOV: NCT06211465.
