Joint tissue plasticity in hemophilia: insights from the Joint Activity and Damage Exam ultrasound protocol

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Background: Progressive arthropathy is a debilitating condition that affects hemophilic joints as a consequence of hemarthroses. However, our understanding of the trajectory of potentially destructive processes at the tissue level remains limited and requires longitudinal imaging studies. Objectives: To longitudinally characterize ultrasonographic joint tissue changes in adults with hemophilia using the Joint Activity and Damage Exam (JADE) protocol, and to examine their relationships with joint health status, hemarthrosis, and serum biomarkers of tissue turnover. Methods: We prospectively studied adults with hemophilia (A or B) of any severity and associated arthropathy at 3 North American sites. We assessed joint health using the Hemophilia Joint Health Score (HJHS) and musculoskeletal ultrasound, as well as the Joint Activity and Damage Exam protocol for direct measurements of osteochondral alterations, cartilage, and soft tissue in the elbows, ankles, and knees at study entry and at ∼12 to 18 and ∼24 to 36 months thereafter. Reported hemarthrosis between study visits was verified by musculoskeletal ultrasound. We analyzed tissue rate changes in healthy (HJHS 0-3) and unhealthy (HJHS ≥ 4) joints, as well as in joints with and without hemarthrosis. Associations between tissue measurements and serially obtained serum biomarkers (C4M, PRO-C4, and C3M) were explored using logistic regression. Results: = .006). Conclusion: Ultrasonographic tissue measurements discriminated between healthy and unhealthy joints at baseline. Measurements revealed a dynamic pattern of tissue plasticity not only in healthy but also in unhealthy and bleeding joints, suggesting potential for reversibility of often-assumed irreversible intra-articular damage in hemophilic joints.

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