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Biomarkers Independently Predict OA Progression


 

FORT LAUDERDALE, FLA. — Prediction of which patients with osteoarthritis will progress has been challenging for clinicians. However, there is promise—researchers identified serum and urinary markers independently associated with 5-year radiographic progression of knee osteoarthritis in a study presented at the World Congress on Osteoarthritis.

Combined use of serum type II collagen helical peptide (Helix-II) and urinary crosslinked C-telopeptide (uCTX-II) might predict disease outcome in these patients, Dr. Patrick Garnero said. Helix-II and CTX-II are type II collagen fragments believed to reflect different osteoarthritis breakdown events from the triple helix and the telopeptide regions of knee cartilage.

Dr. Garnero and his associates previously demonstrated that high urinary levels of these markers were associated with highly destructive hip osteoarthritis (Ann. Rheum. Dis. 2006;65:1639-44). However, urinary markers have limitations, including wide variations in urine dilution and some difficulty obtaining precise sampling among elderly patients.

“Based on this, we launched a study to investigate a new serum-based assay,” said Dr. Garnero, a researcher at Synarc Inc. in Lyon, France.

They compared standing anterior-posterior knee x-rays and Helix-II and CTX-II levels among 83 patients with knee osteoarthritis at baseline and at 2, 3, and 5 years. At baseline, mean age was 62 years and 54% were women. In terms of disease severity, the majority (77%) of patients had a baseline Kellgren-Lawrence (KL) score of 3. The remaining patients scored as follows: KL 0, 13%; KL 1, 5%; KL 2, 4%; and KL 4, 1%.

Joint space was measured on radiographs at the narrowest point. Progression was defined as a reduction in tibiofemoral joint space of 2 mm or a need for total knee replacement during follow-up. A total of 24 patients progressed and 59 did not.

“At baseline and 5 years, both markers were higher in patients with progressive disease. It was not significant at baseline, but the average over 5 years was significant,” Dr. Garnero said at the meeting, sponsored by the Osteoarthritis Research Society International.

For example, after adjustment for age, gender, and body mass index, each standard deviation increase in serum Helix-II was associated with a relative risk of 1.69 for progression. Patients with the highest quartile of serum Helix-II levels and a uCTX-II level above the median had a risk of radiologic progression 8 times higher (RR, 7.79).

“The combined measurement of serum helix-II and uCTX-II may be useful to predict disease outcome in knee osteoarthritis,” Dr. Garnero said.

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