The biomarkers uCTX-II, CS846 and IGF-1 are associated with clinical and ultrasound scores in haemophilic arthropathy: a cross-sectional study.

Haemophilic arthropathy (HA) leads to progressive joint damage. Biomarkers may support early detection and monitoring of disease severity. To assess the association of cartilage and bone turnover biomarkers uCTX-II, CS846, OC, bALP, CTX-I, IGF-1, and CTSG with HA severity in severe and mild haemophilia, as evaluated by clinical and ultrasound scoring. Fifty-three adult patients with severe (n = 27) or mild (n = 26) haemophilia and 52 healthy controls were enrolled. Biomarkers were measured in serum and urine. Joints were assessed using the WFH Physical Examination and HEAD-US scores. uCTX-II was the only biomarker significantly elevated in haemophilia patients and increased progressively with disease severity (median 192.99, 243.34, and 422.88 ng/mmol in controls, mild, and severe haemophilia, respectively; p < 0.001), correlating with both clinical (rho = 0.327, p = 0.028) and HEAD-US (rho = 0.308, p = 0.040) scores in the overall haemophilia group. CS846 levels negatively correlated with clinical (rho = -0.514, p = 0.012) and HEAD-US (rho=-0.609, p = 0.002) scores in mild haemophilia. IGF-1 negatively correlated with clinical (rho=-0.621, p = 0.003) and HEAD-US (rho=-0.646, p = 0.002) scores in severe haemophilia. No significant group differences or associations were observed for OC, bALP, CTX-I, and CTSG. uCTX-II levels increased with HA severity and correlated with joint scores, suggesting its potential as a biomarker of joint damage. Negative correlations with joint scores were observed for CS846 in mild haemophilia, and for IGF-1 in severe haemophilia. CTSG and bone turnover markers showed no association with HA severity. These findings identify uCTX-II, CS846, and IGF-1 as candidate biomarkers for assessing HA severity; longitudinal studies are needed to confirm their clinical utility.