uCTX-II, CS846, and IGF-1 Biomarkers Associate with Haemophilic Arthropathy Severity

Haemophilic arthropathy (HA), a severe complication of haemophilia, leads to progressive and debilitating joint damage, significantly impacting patient quality of life. Current methods for assessing HA severity, such as physical examination and imaging, often detect damage at advanced stages or can be subjective. There is a critical need for non-invasive, objective biomarkers that can facilitate early detection, monitor disease progression, and guide therapeutic interventions. Identifying such biomarkers could enable more timely and effective management of cartilage degeneration and bone remodeling associated with HA, potentially preventing irreversible joint destruction.

This cross-sectional study investigated the association of various cartilage and bone turnover biomarkers with HA severity. Researchers enrolled 53 adult patients with haemophilia (n = 27 severe, n = 26 mild) and 52 healthy controls. Biomarkers, including uCTX-II, CS846, OC, bALP, CTX-I, IGF-1, and CTSG, were measured in serum and urine samples. Joint health was comprehensively assessed using two established scoring systems: the WFH Physical Examination score for clinical evaluation and the HEAD-US score for ultrasound-based structural assessment.

Among the tested biomarkers, uCTX-II was the only one significantly elevated in haemophilia patients, showing a progressive increase with disease severity. Median uCTX-II levels were 192.99 ng/mmol in controls, 243.34 ng/mmol in mild haemophilia, and 422.88 ng/mmol in severe haemophilia (p < 0.001). This biomarker also correlated positively with both clinical (rho = 0.327, p = 0.028) and HEAD-US (rho = 0.308, p = 0.040) scores across the entire haemophilia cohort. CS846 levels exhibited a negative correlation with clinical (rho = -0.514, p = 0.012) and HEAD-US (rho = -0.609, p = 0.002) scores specifically in patients with mild haemophilia. Similarly, IGF-1 negatively correlated with clinical (rho = -0.621, p = 0.003) and HEAD-US (rho = -0.646, p = 0.002) scores in the severe haemophilia group. No significant group differences or associations were observed for OC, bALP, CTX-I, and CTSG.