No abstract

Metabolomic analysis is an emerging new diagnostic tool, which holds great potential for improving the understanding of osteoarthritis (OA)-caused metabolomic shifts associated with systemic inflammation and oxidative stress. The main aim of the study was to map the changes of amino acid, biogenic amine and complex lipid profiles in severe OA, where the shifts should be more eminent compared with early stages. The fasting serum of 70 knee and hip OA patients and 82 controls was assessed via a targeted approach using the AbsoluteIDQ™ p180 kit. Changes in the serum levels of amino acids, sphingomyelins, phoshatidylcholines and lysophosphatidylcholines of the OA patients compared with controls suggest systemic inflammation in severe OA patients. Furthermore, the decreased spermine to spermidine ratio indicates excessive oxidative stress to be associated with OA. Serum arginine level was positively correlated with radiographic severity of OA, potentially linking inflammation through NO synthesis to OA. Further, the level of glycine was negatively associated with the severity of OA, which might refer to glycine deficiency in severe OA. The current study demonstrates significant changes in the amino acid, biogenic amine and low-molecular weight lipid profiles of severe OA and provides new insights into the complex interplay between chronic inflammation, oxidative stress and OA.

Previous studies suggest that metabolic disturbances might be involved in the development of osteoarthritis (OA). Associations have been found between the individual components of metabolic syndrome (MetS) and OA. MetS has been associated with increased oxidative stress (OxS). The study aimed to clarify the role of MetS components in OA and to evaluate the levels of OxS in OA patients and in age-matched controls. Fifty-five patients with end-stage OA (age 63 ± 7 years) prior to hip or knee joint replacement surgery and 55 age-, gender- and body mass index matched controls (61 ± 8 years) were enrolled in the study. Serum levels of glucose, insulin, c-peptide, cholesterols and OxS markers were recorded. Homeostasis model assessment for insulin resistance was used as the proxy measure of insulin resistance. Radiographic severity was assessed using the Kellgren-Lawrence score. The OA patients had higher total peroxide concentration and oxidative stress index [488 (250-612) μmol/L vs. 326 (168-442) μmol/L, p = .011 and 34 (17-51) vs. 20 (11-28), p = .002, respectively] and decreased total antioxidant capacity (1.49 ± 0.27 vs. 1.66 ± 0.27 mmol trolox equivalent/L, p= .008) compared with the controls. In addition, OA group had significantly higher level of C-peptide compared with the controls [1.8 (0.94-2.47) vs. 1.3 (0.46-1.42) ng/mL, p < .001, respectively]. Furthermore, OA radiographic severity was independently associated with LDL-cholesterol (p = .007) and oxidized LDL (p = .022). This study demonstrates that end-stage OA patients have increased levels of OxS and decreased antioxidant capacity. OA is associated with impaired lipid metabolism and dysglycemia. Our results underline the importance OxS and metabolic disturbances in the pathogenesis of OA.

We found decreased levels of acylcarnitines in OA patients. Furthermore, medium-and long-chain acylcarnitines associated independently with arterial stiffness and were related to radiographic severity of OA. Thus, acylcarnities might play an important role in the association between OA and CVD.