Potential biomarkers of haemophilic arthropathy: correlations with compatible additive magnetic resonance imaging scores

Abstract

Introduction: Although biomarkers are useful diagnostic tools to assess joint damage in osteoarthritis and rheumatoid arthritis, few data exist for biomarkers of haemophilic arthropathy. Aim: To evaluate the association between biomarkers and compatible additive magnetic resonance imaging (MRI) scores in patients with severe haemophilia A. Methods: Patients aged 12-35 years with no history of factor VIII (FVIII) inhibitors were enrolled in a controlled, cross-sectional, multinational investigation. Patients received primary or secondary prophylaxis or on-demand treatment with FVIII and underwent MRI on four joints (two ankles, two knees). . Relationships between biomarkers and MRI scores were evaluated using Spearman rank correlation. Results: Biomarkers were assessed in 117 of 118 per-protocol patients. Mean and median CTX-I, COMP, TIMP-1, MMP3, MMP9, and VEGF values were within normal ranges (reference range not available for CS846 in healthy volunteers). No correlations between biomarkers and MRI scores were found, with the exception of CS846, which showed significant correlation in a subgroup of 22 on-demand patients (r = 0.436; P = 0.04). Conclusions: Compatible additive MRI scores showed no clear correlations with any of the potential biomarkers for haemophilic arthropathy in the overall population. CS846 levels were significantly correlated with MRI scores in patients treated on demand.

The Progression of Hemophilic Arthropathy: The Role of Biomarkers

“…On the contrary, a different study found no strong correlation between the same biomarkers and radiological and physical examination of the joint [ 34 ]. Oldenburg et al did not confirm the correlations for serum CS846 and X-ray parameters, on the contrary they found a significant correlation of serum CS846 with MRI score in a small subpopulation [ 45 ]. The relationship of serum cartilage oligomeric matrix protein (COMP) with arthropathy was evaluated in five studies with different results.…”

“…The relationship of serum cartilage oligomeric matrix protein (COMP) with arthropathy was evaluated in five studies with different results. Two studies reported a significant positive association of COMP with JSN on the X-ray while three other studies reported weak negative or no correlations with the severity of HA on the imaging [ 34 , 45 , 60 , 61 , 62 ]. The serum level of COMP was studied in three different studies with contradictory results.…”

“…Considering the bone turnover markers, the most investigated were C-terminal telopeptide of type 1 collagen (CTX-I) and serum osteocalcin. CTX-I was studied in six different studies with heterogeneous results, one study showed a weak but significant association with the degree of arthropathy on X-ray, while the other studies reported non-significant relations [ 34 , 45 , 60 , 72 , 73 ].…”

“…Several markers of joint tissue turnover and formation were investigated with contradictive results. Some studies have found a correlation between the increase of collagen turnover markers and the increase of JSN and PS, unfortunately another study did not confirm this correlation [ 34 , 45 , 60 , 61 , 62 ].…”

Soluble vascular cell adhesion molecular-1 is a potential biological indicator of hemophilic arthropathy

“…The association of soluble biomarkers, including C-terminal telopeptides of type I collagen, cartilage oligomeric matrix protein, TIMP-1, MMP-3, MMP-9, VEGF, and CS846, with these symptoms in hemophilia A have been investigated, but no obvious associations between these soluble biomarkers and MRI joint scores have been reported, except for the positive association of CS846 with MRI joint sores in Oldenburg study. The joint arthropathy in hemophilia A is not a systemic disease, so the analysis of biomarkers of joint arthropathy may be more complex than in RA and OA [31] ; multiple biomarkers can perhaps more effectively and accurately detect the severity of joint arthropathy. Furthermore, whether soluble CS846 and sVCAM-1 levels increase at the same time points or at different time points in hemophilic arthropathy is worth investigating.…”