Increased Bone Formation and Bone Resorption in Patients with Hemophilic Arthropathy: A Cross-Sectional Study

Abstract

Background: Previous studies have revealed that hemophilia patients with severe osteoporosis have more arthropathy symptoms and that their bone metabolism is frequently abnormal. However, it is unclear how to achieve an early diagnosis of hemophilic arthropathy (HA) through abnormalities in bone metabolism.Methods: This study includes 46 patients with HA, 48 healthy controls (HC) and 43 hemophilia without arthropathy (HWA) patients (5 patients were excluded). We measured and compared bone turnover markers (BTMs) including osteocalcin (OC), n-terminal procollagen 1 elongating pro-peptide (t-P1NP) and β-isomerized collagen I-c-terminal peptide breakdown product (β-CTx) of three groups. Receiver operating characteristic (ROC) curve was drawn to obtain the critical value of BTMs for the diagnosis of HA. One-way ANOVA was used to compare the BTMs levels in different degrees of hemophilia. Multivariate linear regression was performed to analyze the correlation between BTMs and clinical severity of HA. Results: The t-P1NP, β-CTx and OC levels of HA and HWA patients were higher than HC, and HA patients had higher t-P1NP and β-CTx levels than HWA patients (p<0.001). But there was no significant difference in OC levels between HA and HWA groups. Logistic regression analysis revealed that high β-CTx and high t-P1NP were significantly associated with HA. ROC curve showed the highest area under the curve was the t-P1NP+β-CTx model (area under the curve was 0.686, the sensitivity was 54.5% and the specificity was 82.5%, the cut-off value was 0.578). Multivariate linear regression analysis indicated that β-CTx was positively correlated with the clinical severity of HA, and t-P1NP levels was negatively correlated with the clinical severity of HA. β-CTx levels decreased with the degree of hemophilia. Conclusions: Increased bone resorption and bone formation were associated with the onset of HA, and the t-P1NP+β-CTx model (β-CTx >775.200 ng/mL and t-P1NP>55.100 ng/mL) contributed to the diagnosis of HA.