Individual participant data meta-analysis of metabolomics on sustained knee pain in primary osteoarthritis patients

Abstract Objectives Knee pain is the major driver for OA patients to seek healthcare, but after pursuing both conservative and surgical pain interventions, ∼20% of patients continue to report long-term pain following total knee arthroplasty (TKA). This study aimed to identify a metabolomic signature...

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Published in:Rheumatology (Oxford, England) England), 2023-05, Vol.62 (5), p.1964-1971
Main Authors: Costello, Christie A, Rockel, Jason S, Liu, Ming, Gandhi, Rajiv, Perruccio, Anthony V, Rampersaud, Y Raja, Mahomed, Nizar N, Rahman, Proton, Randell, Edward W, Furey, Andrew, Kapoor, Mohit, Zhai, Guangju
Format: Article
Language:English
Subjects:
Arthroplasty, Replacement, Knee
Basic Science
Humans
Knee Joint
Metabolomics
Osteoarthritis
Osteoarthritis, Knee - surgery
Pain
Treatment Outcome
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Summary:Abstract Objectives Knee pain is the major driver for OA patients to seek healthcare, but after pursuing both conservative and surgical pain interventions, ∼20% of patients continue to report long-term pain following total knee arthroplasty (TKA). This study aimed to identify a metabolomic signature for sustained knee pain after TKA to elucidate possible underlying mechanisms. Methods Two independent cohorts from St John’s, NL, Canada (n = 430), and Toronto, ON, Canada (n = 495) were included in the study. Sustained knee pain was assessed using the WOMAC pain subscale (five questions) at least 1 year after TKA for primary OA. Those reporting any pain on all five questions were considered to have sustained knee pain. Metabolomic profiling was performed on fasted pre-operative plasma samples using the Biocrates Absolute IDQ p180 kit. Associations between metabolites and pair-wise metabolite ratios with sustained knee pain in each individual cohort were assessed using logistic regression with adjustment for age, sex and BMI. Random-effects meta-analysis using inverse variance as weights was performed on summary statistics from both cohorts. Results One metabolite, phosphatidylcholine (PC) diacyl (aa) C28:1 (odds ratio = 0.66, P = 0.00026), and three metabolite ratios, PC aa C32:0 to PC aa C28:1, PC aa C28:1 to PC aa C32:0, and tetradecadienylcarnitine (C14:2) to sphingomyelin C20:2 (odds ratios = 1.59, 0.60 and 1.59, respectively; all P 
ISSN:1462-0324
1462-0332
DOI:10.1093/rheumatology/keac545