A new marker for osteoarthritis

Osteoarthritis (OA) is a common, crippling age-related disease characterized by the gradual destruction of cartilage cushioning the joints. To assess cartilage erosion, doctors routinely rely on measurement of the joint space width using radiographs. To be visible on an X-ray film, however, significant cartilage degradation must have already occurred. By the time radiographs reveal destruction, the damage to the joint is usually irreversible. Due to this method’s relatively insensitive nature, it also takes at least a year or two to detect progression of damage that has been captured on radiographs.

To improve the early diagnosis and effective treatment of OA, medical researchers have turned to the promise of biochemical markers – molecules released into bodily fluids during the process of tissue turnover. Recently, researchers in the Netherlands identified a novel marker linked to both the prevalence and the progression of OA, particularly at the knee and the hip. They share their breakthrough findings in the August 2004 issue of Arthritis & Rheumatism.

Building on the analysis of cartilage metabolism, the researchers concentrated on peptide fragments of type II collagen. Since type II collagen is located almost exclusively in cartilage, a fragment – abbreviated as CTX-II – was seen as a potential marker for cartilage destruction. To determine the relationship between CTX-II and OA, researchers drew on a large, established sample: 1,235 men and women ages 55 and older enrolled in the Rotterdam Study, a long-term research effort to investigate the incidence of, and risk factors for, chronic disabling diseases. Researchers followed up with participants, whose average was 66, over a time span of six-and-a-half years.

At the study’s onset, 19 percent of the subjects had clear radiographic evidence of OA in at least one knee; 10 percent had OA in at least one hip. At baseline, urine samples from all subjects were assessed for the concentration of CTX-II. The participants were then divided into four groups for further evaluation and continued monitoring, according to their levels of CTX-II.

According to the researchers’ calculations, subjects with a CTX-II level in the highest quartile had a 4-fold increased risk of developing OA in either the knee or hip compared with subjects in the lowest quartile. During the follow-up period, confirmed by repeated radiographs, subjects with the highest concentration of CTX-II were significantly more likely to experience rapid, destructive progression of OA – 6 times more likely at the knee and 8 times more likely at the hip. The subjects with the highest CTX-II levels also had the highest complaints of joint pain. In addition, the researchers found a slight rise in CTX-II concentration with increasing age among women. However, the strong correlation between CTX-II and both the incidence and severity of OA was shown to be independent of age, sex, and body mass index.

“This is the first large follow-up study in which the use of CTX-II as a biomarker for cartilage degradation and disease progression has been investigated,” emphasizes the team’s leading researcher and spokesperson, M. Reijman, MSc. “Based on the results, we conclude that the CTX-II concentration is markedly associated with the prevalence and progression of OA of the knee and hip, and that these associations are independent of known risk factors for radiographic OA. The presence of joint pain seems to augment this relationship,” he notes, “which might reflect the effects of an ongoing OA process. The increase of CTX-II in women after menopause may reflect a protective effect of estrogen against cartilage loss. Further research is necessary to establish the clinical utility of this novel biomarker for OA.”