Suggestive Association Between Tryptophan-indole Metabolic Pathway and Total Joint Arthroplasty Early Revision for Heterogeneous Failure Modes in Patients With Primary Osteoarthritis: A Meta-analysis of Metabolomics
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Published on: December 3, 2017
Ming Liu1, Robert Gill, Rajiv Gandhi
1From the Human Genetics and Genomics, Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada (Liu, Dr. Gill, Huang, and Dr. Zhai); the Osteoarthritis Research Program, Division of Orthopedics, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada (Dr. Gandhi, Dr. Perruccio, Dr. Rampersaud, Dr. Mahomed, and Dr. Kapoor); the Krembil Research Institute, University Health Network, Toronto, Ontario, Canada (Dr. Gandhi, Dr. Perruccio, Dr. Rampersaud, Dr. Mahomed, and Dr. Kapoor); the Discipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada (Dr. Furey); the Institute for Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada (Dr. Perruccio); the Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada (Dr. Perruccio); the Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada (Dr. Rahman); and the Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada (Dr. Kapoor).
Purpose:
This study aimed to identify metabolic biomarkers and pathways that might be associated with total joint arthroplasty (TJA) early revision for heterogeneous failure modes using an individual data meta-analysis of metabolomics.
Methods:
Two independent osteoarthritis (OA) cohorts were included. Revision records of patients with primary knee and hip OA were extracted at an average of 11.1 and 7.8 years after primary TJA, respectively. Preoperative fasting plasma was metabolomically profiled. Concentrations of metabolites/metabolism indicators were natural log-transformed, and their associations with early revision for all reasons in each individual cohort were assessed using logistic regression; the summary statistics from each cohort were then subjected to random-effects meta-analysis modelling.
Results:
Five hundred seventy-two patients with primary OA in The Newfoundland Osteoarthritis Study and 368 in the Longitudinal Evaluation in the Arthritis Program: Osteoarthritis Study were included. The revision rates were 4% and 6%, and mean times to revision were 1.7 and 2.1 years, respectively. No metabolite reached the prespecified significance threshold for multiple testing correction. However, 119 metabolites including choline, tryptophan betaine, indole, ornithine, three acylcarnitines, four cholesteryl esters, two lysophosphatidylcholines, five long-chain diglycerides, and 101 unsaturated (very) long-chain triglycerides were nominally significant with P < 0.05, suggesting potential links between these metabolites and early revision. Among these, indole and one acylcarnitine were positively associated with revision (odds ratio ≥1.73), while all others were negatively associated (odds ratio ≤0.73).
Conclusion:
Overactivation of the tryptophan-indole metabolic pathway may be associated with early revision after primary TJA. However, the findings were suggestive and represented a composite signal from heterogeneous failure modes.
