L F D van Vulpen1, M E R van Meegeren2, G Roosendaal3, N W D Jansen4, J M van Laar5, R E G Schutgens6, S C Mastbergen7, F P J G Lafeber8. 1. Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: L.F.D.vanVulpen-2@umcutrecht.nl. 2. Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: Monique.vanMeegeren@radboudumc.nl. 3. Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: groosend@umcutrecht.nl. 4. Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: n@thalie.nl. 5. Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: J.M.vanLaar@umcutrecht.nl. 6. Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: R.Schutgens@umcutrecht.nl. 7. Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: S.Mastbergen@umcutrecht.nl. 8. Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: F.Lafeber@umuctrecht.nl.
Abstract
OBJECTIVE: Evaluation whether biomarkers of joint damage are sensitive to change shortly after a joint bleed in hemophilia patients and in a canine model of blood-induced joint damage. METHODS: Blood and urine samples were collected from 10 hemophilia patients after they reported a joint bleed: within 2 days, after 3-5 days, and 12-14 days. Additionally, 90 days after the bleed a blood and urine sample was taken and considered to represent baseline condition. Commercial serum and urine biomarker assays were performed: urinary C-terminal telopeptide of type II collagen (uCTX-II), serum cartilage oligomeric matrix protein (sCOMP), serum cartilage cleavage product C1,2C, and serum chondroitin sulfate 846 (sCS846). The same panel of biomarkers was explored in dogs (n = 7) after induction of a first joint bleed by intra-articular blood injections. Biosamples were collected at baseline, day 2, 1 and 2 weeks later. RESULTS: In hemophilia patients, levels of uCTX-II and sCS846 increased 5 days after joint bleeding when compared with baseline (+52%; P = 0.021 and +14%; P = 0.011, respectively). In dogs, uCTX-II increased statistically significant from day 2 to day 7 (from 75% to 155% of baseline; P = 0.018), and sCOMP from baseline to day 2 (+46%; P = 0.028). CONCLUSIONS: This study demonstrates that biochemical markers of joint tissue damage increase shortly after a single joint bleed, both in humans with established hemophilic arthropathy (HA) and in an animal model of joint damage upon a first joint bleed. Biomarkers might be useful in monitoring the impact of a joint bleed and in evaluation of treatment of such bleeds.
OBJECTIVE: Evaluation whether biomarkers of joint damage are sensitive to change shortly after a joint bleed in hemophiliapatients and in a canine model of blood-induced joint damage. METHODS: Blood and urine samples were collected from 10 hemophiliapatients after they reported a joint bleed: within 2 days, after 3-5 days, and 12-14 days. Additionally, 90 days after the bleed a blood and urine sample was taken and considered to represent baseline condition. Commercial serum and urine biomarker assays were performed: urinary C-terminal telopeptide of type II collagen (uCTX-II), serum cartilage oligomeric matrix protein (sCOMP), serum cartilage cleavage product C1,2C, and serum chondroitin sulfate 846 (sCS846). The same panel of biomarkers was explored in dogs (n = 7) after induction of a first joint bleed by intra-articular blood injections. Biosamples were collected at baseline, day 2, 1 and 2 weeks later. RESULTS: In hemophiliapatients, levels of uCTX-II and sCS846 increased 5 days after joint bleeding when compared with baseline (+52%; P = 0.021 and +14%; P = 0.011, respectively). In dogs, uCTX-II increased statistically significant from day 2 to day 7 (from 75% to 155% of baseline; P = 0.018), and sCOMP from baseline to day 2 (+46%; P = 0.028). CONCLUSIONS: This study demonstrates that biochemical markers of joint tissue damage increase shortly after a single joint bleed, both in humans with established hemophilic arthropathy (HA) and in an animal model of joint damage upon a first joint bleed. Biomarkers might be useful in monitoring the impact of a joint bleed and in evaluation of treatment of such bleeds.
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