A candidate biomarker, C-telopeptide fragments of type II collagen (CTX-II) , may be an important early predictor of osteoarthritis (OA) progression, according to a team of Dutch and Danish researchers, whose findings were recently published.

"CTX-II concentration is markedly associated with the prevalence and progression of radiographic OA of the knee and hip, and these associations are independent of known risk factors for radiographic OA ," the authors wrote. "The presence of joint pain seems to augment this relationship, which might reflect the effects of an ongoing OA process."

If CTX-II or another biomarker is confirmed as a predictor of OA progression, the identification of such a marker could help investigators "to detect changes in OA with more reliability and sensitivity, preferably in an early stage," lead author Max Reijman, MSc, told CIAOMed. "The first potential advantage of CTX-II as a biomarker ... is that a shorter follow-up time may be sufficient to observe changes in the joint. In our study we found that CTX-II had a strong association with progression of hip and knee OA. ... These results suggest that CTX-II may be able to identify subjects at high risk for progression of OA."

Mr. Reijman is a research scientist in the departments of internal medicine, epidemiology and biostatistics at Erasmus Medical Center in Rotterdam, The Netherlands. The lead researcher was Huibert A. P. Pols, MD, PhD, head of the department of internal medicine at Erasmus Medical Center and chief investigator of musculoskeletal research of the Rotterdam Study, an ongoing epidemiological investigation.

The investigative team wanted to find an OA biomarker because the gold standard, radiographically confirmed narrowing of the joint space width, is only measurable after irreversible cartilage destruction has already occurred. Because type II collagen is localized almost exclusively in cartilage, and because type II collagen-derived fragments could represent a specific marker for cartilage degradation, the investigators sought to determine whether there was a link between urinary concentrations CTX-II and the prevalence and progression of radiographic OA of the knee and hip.

Therefore, they recruited 1235 men and women who were more than 55 years old and who were enrolled in the Rotterdam Study. The subjects were followed for an average of 6.6 years. The study design defined prevalent radiographic OA as a Kellgren/Lawrence score of more than 2 and progression as a decrease in joint space width.

The investigators found that subjects who had a CTX-II level in the highest quartile were 4.2 times more likely to have radiographic OA of the knee and hip, compared with those who had a CTX-II level in the lowest quartile. They saw an even stronger link between CTX-II levels and radiographic OA for subjects who reported hip pain, who had an odds ratio (OR) of 20.4, whereas those without hip pain had an OR of 3.0. Among subjects who already had OA, those in the highest quartile were 6 times more likely to have progression of radiographic OA at the knee and were 8.4 times more likely to have progression of hip OA. These links were independent of known risk factors for OA, such as age, sex, and body mass index, the investigators stressed.

The validation of CTX-II as an OA biomarker could aid researchers in developing disease-modifying OA drugs (DMOADs) and targeting patients who could benefit from them, Mr. Reijman said. "The hypothesis is that ... DMOADs modify the synthesis of cartilage," he told CIAOMed. "Until now, however, the validity of CTX-II as an early detector of OA signs has not been investigated." He urged more studies to see if CTX-II's value as a biomarker can be confirmed and therefore further OA therapeutics research.

CTX-II also "seems to be a specific marker for cartilage degradation, since CTX-II is associated with joint space narrowing but not with incident osteophytes," Mr. Reijman told CIAOMed. However, he cautioned that "the main limitation of CTX-II always will be that it is not completely specific for OA since it is also associated with rheumatoid arthritis." Furthermore, its presence expresses "the total turnover rate of cartilage and can be modified by cartilage degradation of another joint next to the joint of interest."

Reference:

Reijman M, Hazes JMW, Bierna-Zeinstra SMA, et al. A new marker for osteoarthritis: cross-sectional and longitudinal approach. Arthritis & Rheumatism 2004;50(8):2471-8.