- Email: [email protected]
The lower ratio of the cartilage destruction and synthesis biomarkers is a risk for the radiographic medial knee joint space narrowing in men in early forties without knee osteoarthritis – A three years prospective observational study “sportology core study 1”
S96
Abstracts / Osteoarthritis and Cartilage 25 (2017) S76eS444
compared to RA whereas the V65 vitronectin fragment was statistically significant only for K&L3 compared to RA. In all cases, C3f and the V65 vitronectin fragment levels were never statistically significant in HV compared to RA. Lastly, within OA patients, C3f fragment showed statistically increased expression in the K&L3-4 scores compared to those belonging to the K&L1-2 scores (P-value ¼ 0.032), whereas no difference were observed for the V65 vitronectin fragment (Pvalue ¼ 0.054). Conclusions: We have established and validated a new absolute quantitative method for the simultaneous detection of C3f and the V65 vitronectin peptides in patients with OA. Our data confirm that C3f and the V65 vitronectin fragment are biomarkers of OA severity, but also that C3f fragment is further related to OA severity whereas the V65 vitronectin fragment is more related to early OA detection. 123 THE LOWER RATIO OF THE CARTILAGE DESTRUCTION AND SYNTHESIS BIOMARKERS IS A RISK FOR THE RADIOGRAPHIC MEDIAL KNEE JOINT SPACE NARROWING IN MEN IN EARLY FORTIES WITHOUT KNEE OSTEOARTHRITIS e A THREE YEARS PROSPECTIVE OBSERVATIONAL STUDY “SPORTOLOGY CORE STUDY 1” L. Liu, III y, z, M. Ishijima y, z, H. Kaneko y, R. Sadatsuki y, S. Hada y, A. Yusup y, M. Kinoshita y, H. Arita y, J. Shiozawa y, T. Aoki z, Y. Tamura z, Y. Someya z, M. Nagao y, Y. Takazawa y, H. Ikeda y, H. Watada z, R. Kawamori z, K. Kaneko y, z. y Dept. of Med. for Orthopaedics and Motor Organ, Juntendo Univ. Graduate Sch. of Med., Tokyo, Japan; z Sportology Ctr., Juntendo Univ. Graduate Sch. of Med., Tokyo, Japan Purpose: Abnormalities in type II collagen metabolism play a key process in the pathogenesis of knee osteoarthritis (OA). It has been recently revealed that the cartilage degeneration of the middle age populations is initiated in their thirties, while the prevalence of symptomatic knee OA is sharply increased at around fifty year old. Several cartilage biomarkers have developed to monitor the cartilage metabolism. While the pro-collagen type II C-propeptide (PIICP) is a Cterminal peptide produced by the type II collagen synthesis process, the collagen type II cleavage (C2C) and cross-inked type II collagen Ctelopeptide (CTX-II) are produced by the degradation process of type II collagen. We have conducted the prospective cohort study named the Sportology Core Study1 in our university in which 64 men in forties who didn’t have metabolic diseases and musculoskeletal disorders enrolled and followed up for 3 years to investigate the risk factors of these diseases. The aim of this prospective study was to investigate the parameters among the baseline cartilage metabolic biomarkers associated with the radiographic joint space narrowing of the knee joint of the subjects. Methods: 64 healthy male volunteers (41.6 y in average) who didn’t have any symptoms for knee pain and experience any traumatic episodes for the knee joints were enrolled. A standing, extended anteroposterior view radiograph of both knees were taken at the time of study entry and at 3-years of follow up. The serum PIICP (sPIICP) and C2C (sC2C) levels and urinary level of CTX-II (uCTX-II) were measured at the time of study. The radiographic joint space narrowing was defined when the changes of the radiographic medial joint space width was 0.3 mm or greater in either of the knees during 3-years of follow up, as it is reported that the annual radiographic medial JSN of the knee joint was 0.1 mm in average. The area under the curve (AUC), which is analogous to the area determined by the receiver operating characteristic (ROC) curve, was estimated for the discriminative value of the prediction models. The null hypothesis was that the subjective and objective data could distinguish which subjects would progress of the medial JSW of the knee joint. The criteria for accepting the null hypothesis were AUCs <0.70. Relative risks (RRs) for a subject who would show the radiographic joint space narrowing were calculated. A p value<0.05 was considered to be statistically significant. Results: 47 of 64 subjects were followed for 3 years. Among 47 subjects, 29 and 18 subjects showed the K/L grade 0 and 1 at baseline, respectively. After 3 years of follow-up, 14 of 47 subjects showed the radiographic JSN (P group), while the remaining 33 subjects did not during 3years of follow up (NP group). No significant differences of the sPIICP, sC2C and uCTX-II in P group were observed in comparison to those in NP group. The sC2C/sPIICP ratio of P group (0.26) was significantly decreased in comparison to those of NP group (0.33, p < 0.01). However, no significant difference of the uCTX-II/sPIICP ratio was observed between the P and NP groups. The medial JSW at baseline of the
subjects was associated with the changes of the JSW (DJSW) during 3years of follow up, while the medial JSW at 3-years of follow up was not. The sC2C/sPIICP of the subjects at baseline was associated with the DJSW during 3-years of follow up (r ¼ 0.332, p ¼ 0.022), while sPIICP (r ¼ 0.244, p ¼ 0.098), sC2C (r ¼ 0.143, p ¼ 0.316), and uCTX-II (r ¼ 0.226, p ¼ 0.166) at baseline of the subjects were not. When the subjects were divided into three groups according to the sC2C/sPIICP at baseline (T1, T2 and T3), the age- and BMI- adjusted risk for the radiographic joint space narrowing during 3-years of follow up in T1 was significantly higher than that in the T3 [Odds ratio: 9.8 (95% CI: 1.4 to 67.4)]. The AUCs for the radiographic joint space narrowing during 3-years of follow up evaluated by 0.25 of sC2C/sPIICP at baseline were 0.70 (p < 0.05). The RR at the cut-off level of the radiographic joint space narrowing during 3-years of follow up evaluated by sC2C/sPIICP at baseline was 4.4 (95%CI: 1.2e16.2) at 0.25. Conclusions: It is suggested that OA develops from an imbalance in the synthesis and degradation of type II collagen, and that the ratio of the degradation to the synthesis biomarkers of type II collagen predicts more precisely the progression of OA than the individual biomarkers. In the 3 years’ prospective study of men in early forties without knee OA, the <0.25 of sC2C/sPIICP was the risk for the radiographic medial joint space narrowing of the knee joint in men in early forties without knee OA. 124 TIME BETWEEN INJURY AND SURGERY IS ASSOCIATED WITH HIGHER TYPE-II COLLAGEN TURNOVER 6 MONTHS AFTER ACL RECONSTRUCTION: A PRELIMINARY STUDY H.C. Davis y, J.T. Spang y, R.F. Loeser y, V. Ulici y, J.M. Jordan y, M.S. Harkey y, A. Creighton y, G. Kamath y, J.T. Blackburn y, D.A. Padua y, S. Marshall y, S. Larsson z, L. Lohmander z, B. Pietrosimone y. y UNC Chapel Hill, Chapel Hill, NC, USA; z Lund Univ., Lund, Sweden Purpose: Approximately one-third of individuals who have sustained an anterior cruciate ligament (ACL) injury and undergo ACL reconstruction (ACLR) demonstrate posttraumatic osteoarthritis (PTOA) within the first decade following injury. While ACLR acutely stabilizes the knee joint, it appears that ACLR does little to prevent or delay PTOA onset. The prevalence of radiographic PTOA is similar between ACL injured patients who undergo ACLR compared to those who remain ACL deficient. While some ACL injured individuals can engage in physical activity without ACLR, waiting longer between ACL injury and ACLR may increase the risk of an additional meniscus or chondral injury, potentially hastening the progression of PTOA. It remains unknown if the time between ACL injury and ACLR influences metabolic changes linked to PTOA onset. The purpose of this observational study was to determine whether the period of time between injury and ACLR was associated with biomarkers of cartilage metabolism at the follow-up exam 6 months post ACLR. We hypothesized that increased days between injury and ACLR would be associated with greater blood concentrations at the 6-month follow-up exam of matrix metalloproteinase-3 (MMP3), type-II collagen turnover (ratio of collagen type-II cleavage product [C2C] to collagen type-II propeptide [CPII]; C2C:CPII) and Alanin-Arginine-Glycine-Serine (ARGS) breakdown fragments. Methods: Twenty-two individuals were enrolled into the study during initial presentation in the orthopaedic clinic 6.6 ± 3.7 days following ACL injury (50% females, 21.9 ± 4.5 years old; 23.8 ± 2.6 kg/m2). Each participant elected to undergo ACLR. Days between injury and ACLR were documented on the day of surgery, and none of the participants sustained a second injury within these time points and 6-month follow up. All participants underwent an arthroscopically assisted single incision ACLR with a patellar tendon autograft. Blood was collected at the initial visit and at 6 months following ACLR (197.4 ± 19.8 days). Serum and plasma were immediately separated and stored at -80 C until analysis. Commercially available enzyme-linked immunosorbent assays were used to analyze serum concentrations of collagen type-II cleavage product (C2C) and collagen type-II propeptide (CPII), as well as plasma matrix metalloproteinase-3 (MMP3). Serum Alanin-Arginine-GlycineSerine (ARGS) neopitope was analyzed using an electrochemiluminescence immunoassay. Normality was assessed using a Shapiro-Wilk test. We used separate bivariate Pearson Product Moment correlations (r) to assess associations between normally distributed biochemical outcomes (C2C:CPII, ARGS) and days between injury and ACLR, while Spearman rank-order correlations (r) were used to evaluate
Abstracts / Osteoarthritis and Cartilage 25 (2017) S76eS444
compared to RA whereas the V65 vitronectin fragment was statistically significant only for K&L3 compared to RA. In all cases, C3f and the V65 vitronectin fragment levels were never statistically significant in HV compared to RA. Lastly, within OA patients, C3f fragment showed statistically increased expression in the K&L3-4 scores compared to those belonging to the K&L1-2 scores (P-value ¼ 0.032), whereas no difference were observed for the V65 vitronectin fragment (Pvalue ¼ 0.054). Conclusions: We have established and validated a new absolute quantitative method for the simultaneous detection of C3f and the V65 vitronectin peptides in patients with OA. Our data confirm that C3f and the V65 vitronectin fragment are biomarkers of OA severity, but also that C3f fragment is further related to OA severity whereas the V65 vitronectin fragment is more related to early OA detection. 123 THE LOWER RATIO OF THE CARTILAGE DESTRUCTION AND SYNTHESIS BIOMARKERS IS A RISK FOR THE RADIOGRAPHIC MEDIAL KNEE JOINT SPACE NARROWING IN MEN IN EARLY FORTIES WITHOUT KNEE OSTEOARTHRITIS e A THREE YEARS PROSPECTIVE OBSERVATIONAL STUDY “SPORTOLOGY CORE STUDY 1” L. Liu, III y, z, M. Ishijima y, z, H. Kaneko y, R. Sadatsuki y, S. Hada y, A. Yusup y, M. Kinoshita y, H. Arita y, J. Shiozawa y, T. Aoki z, Y. Tamura z, Y. Someya z, M. Nagao y, Y. Takazawa y, H. Ikeda y, H. Watada z, R. Kawamori z, K. Kaneko y, z. y Dept. of Med. for Orthopaedics and Motor Organ, Juntendo Univ. Graduate Sch. of Med., Tokyo, Japan; z Sportology Ctr., Juntendo Univ. Graduate Sch. of Med., Tokyo, Japan Purpose: Abnormalities in type II collagen metabolism play a key process in the pathogenesis of knee osteoarthritis (OA). It has been recently revealed that the cartilage degeneration of the middle age populations is initiated in their thirties, while the prevalence of symptomatic knee OA is sharply increased at around fifty year old. Several cartilage biomarkers have developed to monitor the cartilage metabolism. While the pro-collagen type II C-propeptide (PIICP) is a Cterminal peptide produced by the type II collagen synthesis process, the collagen type II cleavage (C2C) and cross-inked type II collagen Ctelopeptide (CTX-II) are produced by the degradation process of type II collagen. We have conducted the prospective cohort study named the Sportology Core Study1 in our university in which 64 men in forties who didn’t have metabolic diseases and musculoskeletal disorders enrolled and followed up for 3 years to investigate the risk factors of these diseases. The aim of this prospective study was to investigate the parameters among the baseline cartilage metabolic biomarkers associated with the radiographic joint space narrowing of the knee joint of the subjects. Methods: 64 healthy male volunteers (41.6 y in average) who didn’t have any symptoms for knee pain and experience any traumatic episodes for the knee joints were enrolled. A standing, extended anteroposterior view radiograph of both knees were taken at the time of study entry and at 3-years of follow up. The serum PIICP (sPIICP) and C2C (sC2C) levels and urinary level of CTX-II (uCTX-II) were measured at the time of study. The radiographic joint space narrowing was defined when the changes of the radiographic medial joint space width was 0.3 mm or greater in either of the knees during 3-years of follow up, as it is reported that the annual radiographic medial JSN of the knee joint was 0.1 mm in average. The area under the curve (AUC), which is analogous to the area determined by the receiver operating characteristic (ROC) curve, was estimated for the discriminative value of the prediction models. The null hypothesis was that the subjective and objective data could distinguish which subjects would progress of the medial JSW of the knee joint. The criteria for accepting the null hypothesis were AUCs <0.70. Relative risks (RRs) for a subject who would show the radiographic joint space narrowing were calculated. A p value<0.05 was considered to be statistically significant. Results: 47 of 64 subjects were followed for 3 years. Among 47 subjects, 29 and 18 subjects showed the K/L grade 0 and 1 at baseline, respectively. After 3 years of follow-up, 14 of 47 subjects showed the radiographic JSN (P group), while the remaining 33 subjects did not during 3years of follow up (NP group). No significant differences of the sPIICP, sC2C and uCTX-II in P group were observed in comparison to those in NP group. The sC2C/sPIICP ratio of P group (0.26) was significantly decreased in comparison to those of NP group (0.33, p < 0.01). However, no significant difference of the uCTX-II/sPIICP ratio was observed between the P and NP groups. The medial JSW at baseline of the
subjects was associated with the changes of the JSW (DJSW) during 3years of follow up, while the medial JSW at 3-years of follow up was not. The sC2C/sPIICP of the subjects at baseline was associated with the DJSW during 3-years of follow up (r ¼ 0.332, p ¼ 0.022), while sPIICP (r ¼ 0.244, p ¼ 0.098), sC2C (r ¼ 0.143, p ¼ 0.316), and uCTX-II (r ¼ 0.226, p ¼ 0.166) at baseline of the subjects were not. When the subjects were divided into three groups according to the sC2C/sPIICP at baseline (T1, T2 and T3), the age- and BMI- adjusted risk for the radiographic joint space narrowing during 3-years of follow up in T1 was significantly higher than that in the T3 [Odds ratio: 9.8 (95% CI: 1.4 to 67.4)]. The AUCs for the radiographic joint space narrowing during 3-years of follow up evaluated by 0.25 of sC2C/sPIICP at baseline were 0.70 (p < 0.05). The RR at the cut-off level of the radiographic joint space narrowing during 3-years of follow up evaluated by sC2C/sPIICP at baseline was 4.4 (95%CI: 1.2e16.2) at 0.25. Conclusions: It is suggested that OA develops from an imbalance in the synthesis and degradation of type II collagen, and that the ratio of the degradation to the synthesis biomarkers of type II collagen predicts more precisely the progression of OA than the individual biomarkers. In the 3 years’ prospective study of men in early forties without knee OA, the <0.25 of sC2C/sPIICP was the risk for the radiographic medial joint space narrowing of the knee joint in men in early forties without knee OA. 124 TIME BETWEEN INJURY AND SURGERY IS ASSOCIATED WITH HIGHER TYPE-II COLLAGEN TURNOVER 6 MONTHS AFTER ACL RECONSTRUCTION: A PRELIMINARY STUDY H.C. Davis y, J.T. Spang y, R.F. Loeser y, V. Ulici y, J.M. Jordan y, M.S. Harkey y, A. Creighton y, G. Kamath y, J.T. Blackburn y, D.A. Padua y, S. Marshall y, S. Larsson z, L. Lohmander z, B. Pietrosimone y. y UNC Chapel Hill, Chapel Hill, NC, USA; z Lund Univ., Lund, Sweden Purpose: Approximately one-third of individuals who have sustained an anterior cruciate ligament (ACL) injury and undergo ACL reconstruction (ACLR) demonstrate posttraumatic osteoarthritis (PTOA) within the first decade following injury. While ACLR acutely stabilizes the knee joint, it appears that ACLR does little to prevent or delay PTOA onset. The prevalence of radiographic PTOA is similar between ACL injured patients who undergo ACLR compared to those who remain ACL deficient. While some ACL injured individuals can engage in physical activity without ACLR, waiting longer between ACL injury and ACLR may increase the risk of an additional meniscus or chondral injury, potentially hastening the progression of PTOA. It remains unknown if the time between ACL injury and ACLR influences metabolic changes linked to PTOA onset. The purpose of this observational study was to determine whether the period of time between injury and ACLR was associated with biomarkers of cartilage metabolism at the follow-up exam 6 months post ACLR. We hypothesized that increased days between injury and ACLR would be associated with greater blood concentrations at the 6-month follow-up exam of matrix metalloproteinase-3 (MMP3), type-II collagen turnover (ratio of collagen type-II cleavage product [C2C] to collagen type-II propeptide [CPII]; C2C:CPII) and Alanin-Arginine-Glycine-Serine (ARGS) breakdown fragments. Methods: Twenty-two individuals were enrolled into the study during initial presentation in the orthopaedic clinic 6.6 ± 3.7 days following ACL injury (50% females, 21.9 ± 4.5 years old; 23.8 ± 2.6 kg/m2). Each participant elected to undergo ACLR. Days between injury and ACLR were documented on the day of surgery, and none of the participants sustained a second injury within these time points and 6-month follow up. All participants underwent an arthroscopically assisted single incision ACLR with a patellar tendon autograft. Blood was collected at the initial visit and at 6 months following ACLR (197.4 ± 19.8 days). Serum and plasma were immediately separated and stored at -80 C until analysis. Commercially available enzyme-linked immunosorbent assays were used to analyze serum concentrations of collagen type-II cleavage product (C2C) and collagen type-II propeptide (CPII), as well as plasma matrix metalloproteinase-3 (MMP3). Serum Alanin-Arginine-GlycineSerine (ARGS) neopitope was analyzed using an electrochemiluminescence immunoassay. Normality was assessed using a Shapiro-Wilk test. We used separate bivariate Pearson Product Moment correlations (r) to assess associations between normally distributed biochemical outcomes (C2C:CPII, ARGS) and days between injury and ACLR, while Spearman rank-order correlations (r) were used to evaluate