Molecular Biomarkers Associated With Degenerative Joint Disease in the Knee

Molecular Biomarkers Associated With Degenerative Joint Disease

This investigation describes a novel complex of structural degradation proteins that is associated with pain in individuals with meniscal pathology undergoing arthroscopic partial meniscectomy. The presence of the complex in the synovial fluid of the knee is sensitive and specific for the painful state compared with similar aged controls. The absence of the complex in asymptomatic controls makes it a useful biomarker for the disease state.

Study Overview

• Status: Completed
• Conditions: Cartilage Diseases

Detailed Description

Background: Molecular biomarkers associated with knee pain may be useful as diagnostic tools, prognostic indicators, and surrogate endpoints for therapeutic trials. This study describes a novel complex of structural degradation proteins which are present in the knees of patients with meniscal pathology.

Methods: This prospective cohort study included 30 patients with knee pain, mechanical symptoms, and MRI positive for meniscus tear who elected for arthroscopic partial meniscectomy after failing conservative management. Synovial fluid was aspirated at the time of surgery and assayed for a complex of structural degradation proteins by means of heterogeneous ELISA. The results were compared to knee aspirates from 10 asymptomatic volunteers with no pain. The complex was identified by a proteomic analysis of including multiplexed-bead immunoassay, purification by anion exchange and size exclusion chromatography, and mass spectrometry of individual chromatographic fractions.

• Study Type: Observational
• Enrollment (Actual): 40

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The operative group consisted of patients 18 years of age or greater with a history of knee pain for more than three but less than six months who failed conservative management including NSAIDs, physical therapy, and activity modification.

Description

Inclusion Criteria:

• the presence of mechanical symptoms including locking, catching, or giving way;
• positive physical exam findings including joint line tenderness, McMurray's exam, or Steinman's exam; and
• MRI of the knee positive for meniscus tear in a location correlating with physical examination.

Exclusion Criteria:

• the presence of high grade gonarthrosis including Kellgren-Lawrence grade IV;
• a history of prior knee surgery or trauma; ligamentous incompetence on examination or MRI; and
• diagnosis of inflammatory arthritides, crystalline arthropathies, or other rheumatologic diseases.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Surgical group with knee pain; patients 18 years of age or greater with a history of knee pain for more than three but less than six months who failed conservative management with the presence of mechanical symptoms including locking, catching, or giving way; positive physical exam findings including joint line tenderness, McMurray's exam, or Steinman's exam; and MRI of the knee positive for meniscus tear in a location correlating with physical examination. Exclusion criteria were as follows: the presence of high grade gonarthrosis including Kellgren-Lawrence grade IV; a history of prior knee surgery or trauma; ligamentous incompetence on examination or MRI; and diagnosis of inflammatory arthritides, crystalline arthropathies, or other rheumatologic diseases.
Group 2; volunteer group

Collaborators and Investigators

• Sponsor: Scuderi, Gaetano J., M.D.
• Collaborators: Stanford University
• Investigators: Principal Investigator: Gaetano J Scuderi, MD, Stanford University

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: October 30, 2009
• First Submitted That Met QC Criteria: October 30, 2009
• First Posted (Estimate): November 1, 2009

Study Record Updates

• Last Update Posted (Estimate): November 1, 2009
• Last Update Submitted That Met QC Criteria: October 30, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: pain; biomarker; knee arthroscopy
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Osteoarthritis; Joint Diseases; Cartilage Diseases
• Other Study ID Numbers: Cyt.002