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Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis–related outcomes: results from a longitudinal cohort study

  • Musculoskeletal
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms.

Methods

The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders using propensity score (PS) matching. We developed and used a validated deep learning method for longitudinal thigh segmentation. We assessed the association of DM with 4-year longitudinal muscle degeneration in biomarkers of muscle cross-sectional area (CSA) and contractile percentage (non-fat CSA/total CSA). We further investigated whether DM is associated with 9-year risk of KOA radiographic progression, knee replacement (KR), and symptoms worsening. Finally, we evaluated whether the DM–KOA worsening association is mediated through preceding muscle degeneration.

Results

After PS matching, 698 thighs/knees were included (185:513 with:without DM; average ± SD age:64 ± 8-years; female/male:1.4). Baseline DM was associated with a decreased contractile percent of total thigh muscles and quadriceps (mean difference, 95%CI −0.16%/year, −0.25 to −0.07, and −0.21%/year, −0.33 to −0.08). DM was also associated with an increased risk of worsening KOA-related symptoms (hazard ratio, 95%CI 1.70, 1.18–2.46) but not radiographic progression or KR. The decrease in quadriceps contractile percent partially mediated the increased risk of symptoms worsening in patients with DM.

Conclusions

Baseline DM is associated with thigh muscle degeneration and KOA-related symptoms worsening. As a potentially modifiable risk factor, DM-associated longitudinal thigh muscle degeneration may partially mediate the symptoms worsening in patients with DM and coexisting KOA.

Key Points

• Diabetes mellitus (DM) is associated with worsening knee osteoarthritis (KOA)-related symptoms.

• As a potentially modifiable factor, DM-associated thigh muscle (quadriceps) degeneration partially mediates the worsening of KOA-related symptoms.

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Abbreviations

BMI:

Body mass index

CI:

Confidence interval

CSA:

Cross-sectional area

DM:

Diabetes mellitus

DMOAD:

Disease-modifying osteoarthritis drug

HR:

Hazard ratio

Inter-MAT:

Inter-muscular adipose tissue

Intra-MAT:

Intra-muscular adipose tissue

JSN:

Joint space narrowing

KL:

Kellgren-Lawrence

KOA:

Knee osteoarthritis

KR:

Knee replacement

NASS:

Non-acceptable symptomatic state

OAI:

Osteoarthritis Initiative

PASE:

Physical activity for elderly scale

PS:

Propensity score

SMD:

Standardized mean difference

WOMAC:

Western Ontario and McMaster Universities Arthritis Index

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Acknowledgements

The osteoarthritis initiative, a collaborative project between public and private sectors, includes five contracts N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, and N01-AR-2-2262. This project is conducted by the osteoarthritis initiative project investigators and is financially supported by the National Institutes of Health (NIH). Private funding partners are Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer, Inc. In preparing this manuscript, osteoarthritis initiative project publicly available datasets were used. The results of this work do not necessarily reflect the opinions of the osteoarthritis initiative project investigators, the NIH, or the private funding partners.

Funding

This research was supported by the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Number R01AR079620-01.

Author information

Authors and Affiliations

  1. Musculoskeletal Radiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N Caroline St, JHOC 5165, Baltimore, MD, 21287, USA

    Bahram Mohajer & Shadpour Demehri

  2. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Kamyar Moradi & Mahsa Dolatshahi

  3. Department of Radiology, Boston University School of Medicine, Boston, MA, USA

    Ali Guermazi & Frank W. Roemer

  4. Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Bashir Zikria

  5. Sharif University of Technology, Tehran, Iran

    Nima Najafzadeh

  6. Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Rita R. Kalyani

  7. Department of Radiology, Universitätsklinikum Erlangen & Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

    Frank W. Roemer

  8. Department of Rheumatology, Sorbonne University, INSERM CRSA, AP-HP Hospital Saint Antoine, Paris, France

    Francis Berenbaum

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  1. Bahram Mohajer
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  2. Kamyar Moradi
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  7. Rita R. Kalyani
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Corresponding author

Correspondence to Shadpour Demehri.

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Guarantor

Dr. Shadpour Demehri takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

Conflict of interest

FWR is chief marketing officer and shareholder of Boston Imaging Core Lab (BICL), LLC, and consultant to Calibr – California Institute of Biomedical Research and Grünenthal GmbH. AG is a shareholder of BICL and consultant to Pfizer, TissueGene, MerckSerono, Novartis, Regeneron, and AstraZeneca. FB reports personal fees from AstraZeneca, Boehringer, Bone Therapeutics, CellProthera, Expanscience, Galapagos, Gilead, Grunenthal, GSK, Eli Lilly, Merck Sereno, MSD, Nordic, Nordic Bioscience, Novartis, Pfizer, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, 4P Pharma, grants from TRB Chemedica, non-financial support from 4Moving Biotech, outside the submitted work. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Subjects have given informed consent before participating in the Osteoarthritis Initiative (OAI) project.

Ethical approval

The medical ethics review boards of the University of California, San Francisco (Approval Number: 10-00532) and the four clinical centers of osteoarthritis initiative project recognized the project as Health Insurance Portability and Accountability Act (HIPAA)–compliant.

Methodology

• Retrospective

• Observational

• Multi-center study

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Mohajer, B., Moradi, K., Guermazi, A. et al. Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis–related outcomes: results from a longitudinal cohort study. Eur Radiol 33, 595–605 (2023). https://doi.org/10.1007/s00330-022-09035-4

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