ABSTRACT
The aim of this study was to evaluate serum PIIANP and urinary CTXII as a parameters of type II collagen synthesis and degradation, respectively, in patients with OA knees and to investigate whether the use of these two molecular markers could predict the progression of joint damage evaluated by radiography during a period of 3 years. Sixty patients had symptomatic primary knee OA of Kellgren-Lawrence [K-L] grade I-III and met ACR criteria. These patients were evaluated prospectively for 3 years. Serum PIIANP and urinary CTX-II levels were measured by ELISA at baseline and at study end and their levels compared according to the changes in joint space width [JSW], K-L grade and WOMAC index, over 3 years. Also, we assessed the diagnostic value of those molecular markers and their performance for prediction of radiological progression. Serum and urinary levels also compared with 40 matched healthy subjects as a control group. There were significant decrease in the baseline serum PIIANP [P<0.001] and increase in the baseline urinary excretion of CTX-II [P<0.001] in knee OA patients in comparison with the control, in bilateral than unilateral cases [P<0.05], [P<0.05] and also with increasing the K-L radiological severity of the disease [P<0.05], [P<0.001], respectively. There were significant decrease in the mean baseline serum PIIANP and highly significant increase in the mean baseline urinary excretion of CTXII in progressors [JSW narrowing > 0.5 mm] and in patients showed increase in K-L grading either of the signal or both knees [P<0.05], [P<0.001], respectively. There were significant decrease in the mean study end serum PIIANP and highly significant increase in the mean study end urinary excretion of CTX-II in progressors [JSW narrowing > 0.5 mm] and in patients showed increase in K-L grading either of signal or both knees [P<0.05], [P<0.001], respectively. There were insignificant correlation between serum PIIANP and urinary CTX-II either at the baseline or study end and also insignificant correlation between those molecular markers with disease duration, BMI and WOMAC index [P>0.05]. Urinary CTX-II showed a higher diagnostic sensitivity and specificity [75% - 92%] than serum PIIANP [60% - 90%], respectively. The diagnostic specificity was greatest when both tests were found in combination [96%]. Also, combination of tests showed higher diagnostic sensitivity [92.3%] and specificity [55.3%] for predicting the radiological progression over 3 years than either one alone. In conclusion: using specific molecular markers serum PIIANP and urinary CTX-II, we found that patients with knee OA are characterized by depressed type II collagen synthesis and increased type II collagen degradation. Combining these two molecular markers allows the identification of patients with a high risk of subsequent progression of joint damage