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Research ArticleOsteoarthritis

Phenylalanine Is a Novel Marker for Radiographic Knee Osteoarthritis Progression: The MOST Study

Guangju Zhai, Xianbang Sun, Edward W. Randell, Ming Liu, Na Wang, Irina Tolstykh, Proton Rahman, James Torner, Cora E. Lewis, Michael C. Nevitt, Ali Guermazi, Frank Roemer and David T. Felson
The Journal of Rheumatology January 2021, 48 (1) 123-128; DOI: https://doi.org/10.3899/jrheum.200054
Guangju Zhai
1G. Zhai, PhD, M. Liu, MSc, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada;
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  • ORCID record for Guangju Zhai
  • For correspondence: guangju.zhai@med.mun.ca
Xianbang Sun
2X. Sun, MS, Department of Rheumatology, Boston University School of Medicine, Boston, USA;
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Edward W. Randell
3E. Randell, PhD, Division of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada;
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Ming Liu
1G. Zhai, PhD, M. Liu, MSc, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada;
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Na Wang
4N. Wang, PhD, Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, USA;
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Irina Tolstykh
5I. Tolstykh, MS, M.C. Nevitt, PhD, MPH, Epidemiology and Biostatistics, University of California, San Francisco, USA;
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Proton Rahman
6P. Rahman, MD, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada;
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James Torner
7J. Torner, PhD, Department of Epidemiology, University of Iowa, Iowa City, Iowa, USA;
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Cora E. Lewis
8C.E. Lewis, MD, Department of Epidemiology, University of Alabama, Birmingham, USA;
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Michael C. Nevitt
5I. Tolstykh, MS, M.C. Nevitt, PhD, MPH, Epidemiology and Biostatistics, University of California, San Francisco, USA;
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Ali Guermazi
9A. Guermazi, MD, PhD, F. Roemer, MD, Department of Radiology, Boston University School of Medicine, Boston, USA;
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Frank Roemer
9A. Guermazi, MD, PhD, F. Roemer, MD, Department of Radiology, Boston University School of Medicine, Boston, USA;
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David T. Felson
10D.T. Felson, MD, MPH, Department of Rheumatology, Boston University School of Medicine, Boston, USA, and NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
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Abstract

Objective. To identify plasma markers associated with an increased risk of radiographic knee osteoarthritis

(OA) progression using a metabolomics approach.

Methods. Study participants were from the Multicenter Osteoarthritis Study (MOST) and were categorized into 2 groups based on the presence of baseline radiographic OA. Subjects in group 1 had unilateral knee OA and subjects in group 2 had bilateral knee OA. Progression was defined as a half-grade or greater worsening in joint space width at 30-month follow-up. For group 1, a participant progressed when their OA knee showed radiographic progression and the contralateral knee developed OA; for group 2, a participant progressed when both knees with OA showed radiographic progression. Metabolomic profiling was performed on plasma samples collected at baseline and logistic regression was performed to test the association between each metabolite and knee OA progression after adjustment for age, sex, BMI, and clinic site. Significance was defined as P ≤ 0.0003 in the combined analysis.

Results. There were 234 progressors (57 in group 1 and 177 in group 2) and 322 nonprogressors (206 in group 1 and 116 in group 2) included in the analyses. Among 157 metabolites studied, we found that odds of progression were 1.46 times higher per SD increase of phenylalanine level (95% CI 1.20–1.77, P = 0.0001) in the combined analysis. Sex-specific analysis showed that an association was seen in women (P = 0.0002) but not in men.

Conclusion. Our data suggest that phenylalanine might be a novel plasma marker for higher risk of bilateral radiographic knee OA progression in women.

Key Indexing Terms:
  • knee osteoarthritis
  • metabolomics
  • progression
  • plasma biomarkers
  • radiograph
  • Accepted for publication April 21, 2020.
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Phenylalanine Is a Novel Marker for Radiographic Knee Osteoarthritis Progression: The MOST Study
Guangju Zhai, Xianbang Sun, Edward W. Randell, Ming Liu, Na Wang, Irina Tolstykh, Proton Rahman, James Torner, Cora E. Lewis, Michael C. Nevitt, Ali Guermazi, Frank Roemer, David T. Felson
The Journal of Rheumatology Jan 2021, 48 (1) 123-128; DOI: 10.3899/jrheum.200054

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Phenylalanine Is a Novel Marker for Radiographic Knee Osteoarthritis Progression: The MOST Study
Guangju Zhai, Xianbang Sun, Edward W. Randell, Ming Liu, Na Wang, Irina Tolstykh, Proton Rahman, James Torner, Cora E. Lewis, Michael C. Nevitt, Ali Guermazi, Frank Roemer, David T. Felson
The Journal of Rheumatology Jan 2021, 48 (1) 123-128; DOI: 10.3899/jrheum.200054
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Keywords

KNEE OSTEOARTHRITIS
METABOLOMICS
PROGRESSION
plasma biomarkers
RADIOGRAPH

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Keywords

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  • plasma biomarkers
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