Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study
ABSTRACT Although total joint replacement (TJR) surgery is considered as the most effective treatment for advanced osteoarthritis (OA) patients, up to one‐third of patients reported unfavorable long‐term post‐operative pain outcomes. We aimed to identify metabolic biomarkers to predict non‐responder...
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crwiley:10.1002/jor.24529 2024-09-30T14:38:57+00:00 Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study Costello, Christie A. Hu, Ting Liu, Ming Zhang, Weidong Furey, Andrew Fan, Zhaozhi Rahman, Proton Randell, Edward W. Zhai, Guangju Research and Development Corporation of Newfoundland and Labrador Memorial University of Newfoundland Canadian Institutes of Health Research 2019 http://dx.doi.org/10.1002/jor.24529 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjor.24529 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jor.24529 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jor.24529 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Journal of Orthopaedic Research volume 38, issue 4, page 793-802 ISSN 0736-0266 1554-527X journal-article 2019 crwiley https://doi.org/10.1002/jor.24529 2024-09-05T05:08:35Z ABSTRACT Although total joint replacement (TJR) surgery is considered as the most effective treatment for advanced osteoarthritis (OA) patients, up to one‐third of patients reported unfavorable long‐term post‐operative pain outcomes. We aimed to identify metabolic biomarkers to predict non‐responders to TJR using a metabolomics approach. TJR patients were recruited and followed‐up at least 1‐year post‐surgery; TJR outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function subscales. Targeted metabolomic profiling was performed on plasma samples collected pre‐surgery and pairwise metabolite ratios, as proxies for enzymatic reactions, were calculated. Association tests were performed between each metabolite ratio and non‐responders. The metabolome‐wide significance was defined as p < 2 × 10 −5 . A total of 461 TJR patients due to primary OA were included in the analysis. Fifteen percent of patients were classified as pain non‐responders; 16% were classified as function non‐responders. Lower baseline WOMAC pain and function scores were significantly associated with pain and function non‐responders, respectively (both p < 0.03). Two metabolite ratios were significantly associated with pain non‐responders; acetylcarnitine (C2) to phosphatidylcholine acyl‐alkyl C40:1 (PC ae C40:1) was five times higher in pain non‐responders whereas phosphatidylcholine diacyl C36:4 (PC aa C36:4) to isoleucine was twenty one times lower in pain non‐responders than responders (all p ≤ 1.93 × 10 −5 ). One metabolite ratio, glutamine to isoleucine, was significantly lower in function non‐responders than responders (eight times lower; p = 1.08 × 10 −5 ). Three metabolite ratios (C2 to PC ae C40:1, PC aa C36:4, and glutamine to isoleucine) related to inflammation and muscle breakdown could be considered as novel plasma markers for predicting non‐responders to TJR and warrant further investigation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop ... Article in Journal/Newspaper Newfoundland Wiley Online Library Journal of Orthopaedic Research 38 4 793 802 |
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English |
description |
ABSTRACT Although total joint replacement (TJR) surgery is considered as the most effective treatment for advanced osteoarthritis (OA) patients, up to one‐third of patients reported unfavorable long‐term post‐operative pain outcomes. We aimed to identify metabolic biomarkers to predict non‐responders to TJR using a metabolomics approach. TJR patients were recruited and followed‐up at least 1‐year post‐surgery; TJR outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function subscales. Targeted metabolomic profiling was performed on plasma samples collected pre‐surgery and pairwise metabolite ratios, as proxies for enzymatic reactions, were calculated. Association tests were performed between each metabolite ratio and non‐responders. The metabolome‐wide significance was defined as p < 2 × 10 −5 . A total of 461 TJR patients due to primary OA were included in the analysis. Fifteen percent of patients were classified as pain non‐responders; 16% were classified as function non‐responders. Lower baseline WOMAC pain and function scores were significantly associated with pain and function non‐responders, respectively (both p < 0.03). Two metabolite ratios were significantly associated with pain non‐responders; acetylcarnitine (C2) to phosphatidylcholine acyl‐alkyl C40:1 (PC ae C40:1) was five times higher in pain non‐responders whereas phosphatidylcholine diacyl C36:4 (PC aa C36:4) to isoleucine was twenty one times lower in pain non‐responders than responders (all p ≤ 1.93 × 10 −5 ). One metabolite ratio, glutamine to isoleucine, was significantly lower in function non‐responders than responders (eight times lower; p = 1.08 × 10 −5 ). Three metabolite ratios (C2 to PC ae C40:1, PC aa C36:4, and glutamine to isoleucine) related to inflammation and muscle breakdown could be considered as novel plasma markers for predicting non‐responders to TJR and warrant further investigation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop ... |
author2 |
Research and Development Corporation of Newfoundland and Labrador Memorial University of Newfoundland Canadian Institutes of Health Research |
format |
Article in Journal/Newspaper |
author |
Costello, Christie A. Hu, Ting Liu, Ming Zhang, Weidong Furey, Andrew Fan, Zhaozhi Rahman, Proton Randell, Edward W. Zhai, Guangju |
spellingShingle |
Costello, Christie A. Hu, Ting Liu, Ming Zhang, Weidong Furey, Andrew Fan, Zhaozhi Rahman, Proton Randell, Edward W. Zhai, Guangju Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study |
author_facet |
Costello, Christie A. Hu, Ting Liu, Ming Zhang, Weidong Furey, Andrew Fan, Zhaozhi Rahman, Proton Randell, Edward W. Zhai, Guangju |
author_sort |
Costello, Christie A. |
title |
Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study |
title_short |
Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study |
title_full |
Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study |
title_fullStr |
Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study |
title_full_unstemmed |
Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study |
title_sort |
metabolomics signature for non‐responders to total joint replacement surgery in primary osteoarthritis patients: the newfoundland osteoarthritis study |
publisher |
Wiley |
publishDate |
2019 |
url |
http://dx.doi.org/10.1002/jor.24529 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjor.24529 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jor.24529 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jor.24529 |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_source |
Journal of Orthopaedic Research volume 38, issue 4, page 793-802 ISSN 0736-0266 1554-527X |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/jor.24529 |
container_title |
Journal of Orthopaedic Research |
container_volume |
38 |
container_issue |
4 |
container_start_page |
793 |
op_container_end_page |
802 |
_version_ |
1811641524653391872 |