Development of a Model for the Diagnosis of Early Knee Osteoarthritis (MoDEKO)

Introduction:

The purpose of this study was to develop a tool for the diagnosis of early knee osteoarthritis based on symptoms, knee examination findings and osteoarthritis risk factors. Secondarily, we were interested in assessing whether the addition of biomarker (laboratory test) information would help in the diagnosis of early knee osteoarthritis.

Why Do This Research?

Osteoarthritis is the most common joint disease. It affects 10% of people over the age of 63 years and when it occurs in the knee, it causes pain and difficulty with walking. Osteoarthritis starts when people are in their 40s and 50s. However, they are often not diagnosed with it until many years later, because x-rays only begin to detect osteoarthritis when it is already quite advanced. MRI (magnetic resonance imaging) detects osteoarthritis at a much earlier stage than x-rays. In the MoDEKO study, we used MRI in people with knee pain to determine whether they have osteoarthritis and whether the disease is at an early or advanced stage.

The assessment ‘tool’ developed in the MoDEKO study allows for a diagnosis of osteoarthritis at an early stage. Such a tool will play an important role in evaluating persons with early knee osteoarthritis to gain a better understanding of the progression of disease, risk factors for progression, and will lead to the evaluation of new treatments in early osteoarthritis.

Who Is Being Studied?

255 men and women, age 40-79 years old, with knee pain were randomly (by chance) selected from the general population in the Greater Vancouver area.

How Is It Done?

Participants were assessed for pain characteristics, how well they can perform activities such as walking, and for risk factors of osteoarthritis such as age, weight, previous knee injury or surgery, occupation and family history. All participants had their knees examined using standardized examination techniques (see Evaluation and Standardization of the Knee Examination [ESKE] study) and they underwent an x-ray and MRI of the more painful knee. Blood and urine samples were collected and analyzed for biomarkers. Biomarker tests are only available at specialized laboratories.

Subjects were categorized as advanced, early or no osteoarthritis based on the degree of cartilage degeneration seen on MRI. With this information, an assessment "tool" was developed to identify subjects with early knee osteoarthritis and to differentiate them from those with advanced osteoarthritis and from those with no osteoarthritis.

What Was Found?

87% of participants had osteoarthritis based on MRI assessment. The majority of these had early stage disease with abnormal MRI findings but with normal x-ray. This means that the majority of participants would not have been diagnosed based on x-ray alone.

The assessment tool that was developed was able to classify participants into the different subgroups of osteoarthritis with good accuracy, particularly for early stage disease, where the tool correctly identified 76% of cases, and for advanced stage of disease, where the tool correctly identified 85% of cases. The tool that was developed included information based on clinical questions, knee examination findings, x-ray and 4 biomarkers. We also found that the tool did not perform as well without the biomarker information.

Why Is This Relevant To People Living With Arthritis?

Osteoarthritis is the most common form of arthritis and its occurrence will only increase with the aging of the Canadian population. Because osteoarthritis is common and causes difficulty with many aspects of daily living, the cost to the individual and to society is tremendous.

The assessment "tool" developed in this study will allow for a diagnosis of osteoarthritis at an early stage. Such a tool will play an important role in evaluating persons with early knee osteoarthritis to gain a better understanding of the progression of disease, risk factors for progression, and will lead to the evaluation of new treatments in early osteoarthritis.

Are Consumers Involved?

Consumers are involved as participants in this research study.

Who Helped Pay For The Research?

This research was funded by the Canadian Institutes of Health Research, the Canadian Arthritis Network and The Arthritis Society of Canada.

Publications / Presentations

Results for this study were presented at the

- American College of Rheumatology meeting, San Diego, CA, November 2005;
- Canadian-Mexican Rheumatology Congress, Acapulco, Mexico, February 2006;
- American College of Rheumatology meeting, Washington, DC, November 2006;
- Osteoarthritis Research Society International World Congress, Prague, Czech Republic, December 2006.
- Canadian Rheumatology Association Annual meeting, Kananaskis, AB, February 2009;
- Osteoarthritis Research Society International World Congress, Montreal, QC, September 2009
- Osteoarthritis Research Society International World Congress, Brussels, Belgium, September 2010

Published abstracts:

Cibere J, Trithart S, Kopec JA, Thorne A, Zhang H, Singer J, Combes V, Guermazi A, Peterfy C, Nicolaou S, Munk P, Wong H, Esdaile JM. Pre-radiographic knee osteoarthritis is common in people with knee pain: Results from a population-based survey. Arthritis Rheum 2005;52(suppl):S509.

Cibere J, Zhang H, Thorne A, Poole AR, Lobanok T, Kopec JA, Singer J, Wong H, Trithart S, Combes V, Guermazi A, Peterfy C, Nicolaou S, Munk P, Esdaile JM. Biomarkers differentiate radiographic and pre-radiographic symptomatic knee osteoarthritis from symptomatic controls: Results from a population-based study using MRI. J Rheumatol 2006;33(2):398.

Cibere J, Zhang H, Thorne A, Garnero P, Poole AR, Lobanok T, Kopec JA, Singer J, Wong H, Guermazi A, Peterfy C, Nicolaou S, Munk P, Esdaile JM. Urine CTX-II and urine C2C are differentially associated with radiographic and pre-radiographic knee osteoarthritis (OA): Results of a population-based study using MRI. Arthritis Rheum 2006;54:S160.

Cibere J, Zhang H, Thorne A, et al. Identification of early knee osteoarthritis: Results from the development of a Model for the Diagnosis of Early Knee Osteoarthritis (MoDEKO) study. Osteoarthritis Cartil 2006;14(Suppl B):S124.

Ip S, Cibere J, Sayre EC, Guermazi A, Nicolaou S, Wong H, Thorne A, Singer J, Kopec J, Esdaile JM. Frequency of bone marrow edema in knee osteoarthritis and association with pain severity: Results from a population-based study. J Rheumatol 2009;36:S2609.

Sayre EC, Singer J, Thorne A, Wong H, Kopec JA, Esdaile JM, Guermazi A, Nicolaou S, Cibere J. Comparing magnetic resonance imaging-based definitions of knee osteoarthritis to x-ray-based Kellgren-Lawrence Grade for predicting disease severity. Osteoarthritis Cartilage 2009;17(Suppl 1):S163.

 Crema MD, Guermazi A., Sayre EC, Roemer FW, Marra MD, Wong H, Thorne A, Singer J, Esdaile JM, Kopec JA, Nicolaou S, J. Cibere. The association of magnetic resonance imaging (MRI)-detected structural pathology of the knee with crepitus in a population-based cohort with knee pain: the MoDEKO study. Osteoarthritis Cartilage 2010;18(suppl 2):S176.

Published Papers:

Cibere J, Zhang H, Garnero P, et al. Association of Biomarkers With Pre–Radiographically Defined and Radiographically Defined Knee Osteoarthritis in a Population-Based Study. Arthritis Rheum 2009;60:1372-80.

Cibere J, Zhang H, Thorne A, Wong H, Singer J, Kopec J, Guermazi A, Peterfy C, Nicolaou S, Munk PL, Esdaile JM. Association of clinical findings with pre-radiographic and radiographic knee osteoarthritis in a population-based study. Arthritis Rheum 2010 (in press).

Team Members

Principal Investigator:

Jolanda Cibere   MD, PhD
Research Scientist, ARC 

Co-Investigators

John M. Esdaile  MD, MPH
Scientific Director, ARC

Jacek Kopec   MD, PhD
Research Scientist, ARC

Matthew Liang   MD, MPH

Joel Singer MD, PhD

Anona Thorne MSc

Hubert Wong PhD

Hongbin Zhang MSc

Peter Munk MD

Savvakis Nicolaou MD

Charles Peterfy MD, PhD

Ali Guermazi, MD

Collaborators:

A. Robin Poole PhD, DSc

Patrick Garnero, PhD, DSc

Virginia Kraus MD, PhD

Tore Saxne MD, PhD

Study Coordinators:

Kelly McGorm, Pam Rogers, Sherry Trithart, Victoria Combes, Chinh Nguyen

Other Institutions Involved:

University of British Columbia
Vancouver, BC    Canada

Centre for Health & Evaluation Outcome Sciences
Vancouver, BC    Canada

Vancouver Hospital & Health Sciences Centre
Vancouver, BC    Canada

Synarc Inc
San Francisco, CA   USA

Joint Diseases Laboratory
Shriners Hospitals for Children
McGill University
Montreal, QC    Canada

Centre of National Research on Disability and Rehabilitation Medicine (CONROD)
University of Queensland
Brisbane    Australia