Utilizing metabolomics to identify potential biomarkers and perturbed metabolic pathways in osteoarthritis: A systematic review

Purpose: Osteoarthritis (OA) is a joint disease that is clinically diagnosed using components of history, physical exam, and characteristic radiographic findings, such as joint space narrowing. Currently, there are no laboratory findings that are specific to a diagnosis of OA. The purpose of this systematic review is to evaluate the state of current studies of metabolomic biomarkers that can aid in the diagnosis and treatment of OA. Methods: Articles were gathered from PubMed and Web of Science using the search terms "osteoarthritis" and "biomarkers" and "metabolomics". Last search of databases took place December 3rd, 2022. Duplicates were manually screened, along with any other results that were not original journal articles. Only original reports involving populations with diagnosed primary or secondary OA (human participants) or surgically induced OA (animal participants) and a healthy control group for comparison were considered for inclusion. Metabolites and metabolic pathways reported in included articles were then manually extracted and evaluated for importance based on reported a priori p-values and/or area under the receiver-operator curve (AUC). Results: Of the 161 results that were returned in the database searches, 43 unique articles met the inclusion criteria. Articles were categorized based on body fluid analyzed: 6 studies on urine samples, 13 studies on plasma samples, 11 studies on synovial fluid (SF) samples, 11 studies on serum samples, 1 study on both synovial fluid and serum, and 1 study that involved both plasma and synovial fluid. To synthesize results, individual metabolites, as well as metabolic pathways that involve frequently reported metabolites, are presented for each study. Indications as to whether metabolite levels were increased or decreased are also included if this data was included in the original articles. Conclusions: These studies clearly show that there are a wide range of metabolic pathways perturbed in OA. For this period, there was no consensus on a single metabolite, or panel of metabolites, that would be clinically useful in early diagnosis of OA or distinguishing OA from a healthy control. However, many common metabolic pathways were identified in the studies, including TCA cycle, fatty acid metabolism, amino acid metabolism (notably BCAA metabolism and tryptophan metabolism via kynurenine pathway), nucleotide metabolism, urea cycle, cartilage matrix components, and phospholipid metabolism. Future research is needed to define effective clinical biomarkers of osteoarthritis from metabolomic and other data.