Serum phospholipids and sphingolipids are linked to early-stage osteoarthritis by lipidomic profiling

Osteoarthritis (OA) is associated with abnormal lipid metabolism, wherein elevated levels of phospholipids (PLs) and sphingolipids (SLs) in human and canine synovial fluid (SF) have been observed. The aim of this lipidomic study was to evaluate how closely blood lipid levels reflect changes in SF, building on previous findings. Lipids were extracted from knee SF and serum of 44 joint-healthy donors and 58 early (eOA) or late OA (lOA) patients. By electrospray ionization tandem mass spectrometry (ESI-MS/MS), we quantified the extracted lipids and conducted comprehensive statistical analyses. Human SF and serum had similar PL and SL compositions. Quantifying 91 lipid species from 6 major classes revealed OA-related changes in serum, with the lowest levels in healthy controls and elevated levels already in the eOA cohort. Generally, serum PL and SL levels were 3–12 times higher than in SF. Specific PL species were elevated in both SF and serum of eOA and lOA patients compared to healthy controls, while nearly 10% of the PL species measured were higher exclusively in the serum of OA patients. The significant lipidomic alterations that were detected at an average Outerbridge score of less than 2 suggest that certain serum PLs may serve as indicators for monitoring the early stages of OA even before radiologic detection is possible. With 10% of PL species elevated only in OA serum, our data implicate the existence of a systemic response that parallels the local lipid metabolic response to OA.