Concentrations of serum cartilage oligomeric matrix protein after anterior cruciate ligament injury.

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Concentrations of serum cartilage oligomeric matrix protein after anterior cruciate ligament injury. -Comparing with MRI T2 mapping technique- Yohei Nishida, M.D. 1) Yusuke Hashimoto, M.D. Ph.D. 1), Shinya Yamasaki, M.D. Ph.D. 2) Hiroaki Nakamura, M.D. Prof. 1) 1)Dept. of Orthopaedics Surgery, Osaka City University Graduate School of Medicine 2) Dept. of Orthopaedics Surgery, Osaka City General Hospital I have no financial conflicts to disclose.

There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA). Introduction <For early diagnosis> Cartilage oligomeric matrix protein (COMP) A degradation of product of articular cartilage, may be able to detect early OA before radiographic changes become apparent. Aim: To measure serum COMP levels for ACL injured patients. To examine the potential utility of COMP as a diagnostic biomarker for early knee OA.

Method 47 patients who underwent ACL reconstruction were enrolled. -within 12 months after injury -without OA at baseline (K-L grade 0 or 1) -underwent blood test for serum COMP <Evaluation> Serum samples; COMP and MMP-3 were obtained before and 1 year after surgery. Radiographic; K-L radiographic grade and MRI- T2 mapping were calculated for each patient at baseline and at 1-year follow-up.

Method <Region of Interest> -mid-sagittal one slicemedial/lateral femoral condyle (MFC/LFC) medial/lateral tibia plateau (MTP/LTP) patellofemoral joint (P/F) <Analysis> The relationship between serum COMP levels and age, pre-activity level using Tegner activity scale (TAS), serum MMP-3 levels, T2 mapping were assessed by the calculation of Pearson correlation coefficients.

Results Demographic data Patients N=47 Age Sex Time from injury to surgery Meniscus 22.4±9.1 yo Male:18 Female:29 3.8±2.7Month injured:26 intact:21 KL 0:40 Ⅰ:7 TAS 5.8(3-8) scomp(ng/ml) 151.6±57.3

Results Pre Post 1Y P value KT(mm) 5.7±1.6 1.0±1.8 <0.001 smmp-3(ng/ml) 34.8±17.7 29.2±10.3 0.85 MFC(ms) 46.4±2.9 47.1±2.8 0.02 LFC(ms) 46.3±3.2 47.2±3.3 0.14 MTP(ms) 43.3±2.7 43.6±3.0 0.21 LTP(ms) 39.5±3.6 39.7±3.5 0.72 P(ms) 43.4±2.2 43.3±2.8 0.28 F(ms) 47.8±2.6 49.0±3.1 0.01

Correlation Preoperative serum COMP- CC P value Age 0.28 0.05 TAS 0.21 0.17 Time from injury to surgery -0.21 0.15 KL 0.58 <0.001 Preoperative MMP-3 0.35 0.017 Postoperative MMP-3-0.2 0.14 The serum MMP-3 at baseline were correlated with the preoperative serum COMP level.

Correlation Preoperative serum COMP and preoperative MRI T2 mapping- ROI CC P value MFC 0.25 0.09 LFC 0.05 0.74 MTP 0.29 0.05 LTP 0.13 0.39 P 0.20 0.27 F 0.09 0.53 The T2 values of MTP at baseline was correlated with the preoperative serum COMP level.

Correlation Preoperative serum COMP and postoperative MRI T2 mapping- ROI CC P value MFC 0.33 0.02 LFC -0.04 0.77 MTP 0.10 0.49 LTP 0.25 0.09 P 0.20 0.18 F 0.32 0.03 The T2 values of MFC and F at 1 year after surgery were correlated with the preoperative serum COMP level.

Discussion <Previous report about COMP> COMP levels positively correlated with age, synovitis, OA. <COMP with ACL injury case> Higher than control subjects <This study> Preoperative COMP Preoperative MMP-3 It may indicate the serum COMP is correlated with joint inflammation or synovitis after ACL injury.

Discussion <COMP as a diagnostic marker> Preoperative COMP pre T2 value of MTP pre KL grade <COMP as a prognostic marker> Preoperative COMP post T2 value of MFC and F It may indicate the serum COMP is sensitive to articular damage.the COMP is useful to detect early OA. <limitation> 1Lack of control group 2Short time follow-up (1 year) 3Not investigated the causal relationship between the serum COMP and T2 value

Conclusion We measured the serum COMP levels to examine the potential utility of COMP as a diagnostic biomarker for early knee OA. The serum COMP correlated with preoperative synovitis and T2 values. It may be useful to detect early OA for ACL injured patient.

References Henning Madry et al. Early osteoarthritis of the knee. Knee Surgery, Sports Traumatology, Arthroscopy 2016;24;1753-1762 Bauer et al. Classification of osteoarthritis biomarkers :a proposed approach. Osteoarthritis and cartilage 2006;14;723-7 Culvenor et al. Early knee osteoarthritis is evident one year following anterior cruciate ligament reconstruction: a magnetic resonance imaging evaluation. Arthritis Rheumatol 2015;67;946-55 Verma P et al. Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic marker. J Orthop Res 2013;31;999-1006 Zivanovic S et al. Cartilage oligomeric matrix protein inflammation biomarker in knee osteoarthritis. Bosn J Basic Med Sci 2011;11;27-32 Hoch JM et al. Serum cartilage oligomeric matrix protein (scomp) is elevated in patients with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis and Cartilage 2011;19;1396-1404 Palmieri-Smith RM et al. Early cartilage changes after anterior cruciment ligament injury: evaluation with imaging and serum biomarkers A pilot study. Arthroscopy 2016;32;1309-18