Can joint fluid metabolic profiling (or "metabonomics") reveal biomarkers for osteoarthritis and inflammatory joint disease?: A systematic review

Abstract

Aims: Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes.

Methods: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF.

Results: The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars.

Conclusion: The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data.Cite this article: Bone Joint Res. 2020;9(3):108-119.

Keywords: Inflammatory arthropathies; Metabolic profiling; Metabonomics; Osteoarthritis; Rheumatoid arthritis.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) search and screening flowchart for the role of metabolic profiling in human synovial fluid research. *Excerpta Medica Database, Amsterdam, The Netherlands.

Fig. 2

Metabolic network analysis of all the putative biomarkers identified in this systematic review demonstrating the associated metabolic pathways. All metabolites with a red outline were putative biomarkers. a) Putative biomarkers identified in osteoarthritic synovial fluid (SF). Those in green were raised and those in orange were reduced in osteoarthritic SF compared to an asymptomatic control group. b) Putative biomarkers identified in inflammatory arthropathies. Those in green and blue were raised in reactive arthritis (ReA) compared to an asymptomatic control group; those in blue were also raised in ReA compared to rheumatoid arthritis (RA); valine (in yellow) was raised in ReA compared to RA. ADP, adenosine 5'-diphosphate; AMP, adenosine 5'-monophosphate; CoA, coenzyme A; GD1a, N-acetylneuraminyl-D-galactosyl-N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide; Gly, glycine; GM1, D-galactosyl-N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide; GM2, N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide; GM3, (N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide; GM4, N-acetylneuraminyl-galactosylceramide; GSH, reduced glutathione; LacCer, lactosylceramide; L-Asp, L-aspartic acid; Neu5Ac, N-acetylneuraminic acid; NH3, ammonia; PRPP, 5-phosphoribosyl 1-pyrophosphate; R-COOH, carboxylic acid; ThPP, thiamin pyrophosphate; TPP, thiamin pyrophosphate.