Osteoarthritis (OA) is a nearly ubiquitous disease of aging which exacts an enormous disability burden on the elderly population. While the diagnosis and quantification is OA is typically made based upon radiographic and clinical criteria, the availability of a surrogate biomarker would be of great value to researchers and clinicians investigating and treating spinal arthritis. Much as cardiac enzyme analysis has advanced the field of cardiovascular care and research, an economically viable OA biomarker would allow quantification of systemic disease burdens in population cross sections, as well as longitudinally within an individual, to track disease interventions.
In a recent article, Kraus, et al (PLoS ONE 5(3):e9739) at Duke University investigated 461 females with symptomatic hand OA. The investigators sought to assess the overall OA disease burden by investigating 7 distinct anatomic areas in the hands, knees, hips, and lumbar spine with plain radiographs. The Kellgren Lawrence (KL) grading scale, which is a matrix to assess the degree of both joint space narrowing and osteophyte formation was then applied to determine the degree of radiographic abnormality. Overall and joint-specific disease were quantified and compared with specific serum and urine biomarkers found to be associated with joint degeneration, including: serum hyaluronan (sHA), serum cartilage oligomatrix protein (sCOMP), and urinary C-telopeptide of type II collagen (uCTX2). All 3 biomarkers were assessed using the enzyme-linked immunosorbent assay method.
The investigators found the both sHA and sCOMP were excellent indicators of disease burden as ascertained by the KL matrix. These markers were predictive of both joint space narrowing as well as osteophyte formation. However, sCOMP levels were found to be inversely correlated with radiographic evidence of joint space narrowing (while predictive for osteophyte density). Interestingly, the biomarker uCTX2 was found to be independent of age; and specific joints, such as the carpal-metacarpal joints, were found to be more readily predicted by this phenotyping method. The authors thus conclude that, as with other disease states, analysis of a panel or spectrum of breakdown markers may be more helpful than any single test.
Specific drawbacks of this study were that the sample included only women identified primarily with wrist, hand, and finger problems, thus limiting the scope of OA phenotypes investigated. The limitation to 3 biomarkers also renders the analysis preliminary. Finally, the clinical significance of radiographically diagnosed OA limits the clinical relevance of this investigation. Nevertheless, the use of serum and urine biomarkers remains a promising avenue of pursuit, as this noninvasive method for measuring disease burden may prove to be a very effective method for: 1) determining the early efficacy of experimental interventions; 2) early screening for OA; and 3) phenotyping disease variants within a diseased population.
MICHAEL Y WANG