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A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis.
Luo, Y, Samuels, J, Krasnokutsky, S, Byrjalsen, I, Kraus, VB, He, Y, Karsdal, MA, Abramson, SB, Attur, M, Bay-Jensen, AC
Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology. 2021;(1):10
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Abstract
BACKGROUND Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation. MATERIALS AND METHODS The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width. RESULTS In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4-8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011). CONCLUSION Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug. LEVEL OF EVIDENCE Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.
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Relationship between weight loss in obese knee osteoarthritis patients and serum biomarkers of cartilage breakdown: secondary analyses of a randomised trial.
Bartels, EM, Henrotin, Y, Bliddal, H, Centonze, P, Henriksen, M
Osteoarthritis and cartilage. 2017;(10):1641-1646
Abstract
OBJECTIVE To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population. DESIGN 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0, 8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and symptoms by the Knee Osteoarthritis Outcome Score (KOOS) questionnaire. Changes from week 0 and association between changes from baseline in body weight and Coll2-1, Fib3-2, and the 5 KOOS domains were assessed at all time points. RESULTS Coll2-1 changes from baseline showed a decrease at week 8 (P = 0.0002), no change at week 16 (P = 0.49), and an increase at week 68 (P = 0.036). Fib3-2 showed an increase from baseline at week 8 (P = 0.0015) and 16 (P < 0.0001), but none at week 68 (P = 0.23). No statistically significant correlations were found between changes in body weight and Coll2-1 and Fib3-2 at any time point (r < 0.05; P > 0.49). At all time-points there were significant positive correlations between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8, 16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04, respectively). CONCLUSION The clinical improvement after a substantial weight loss and weight maintenance in KOA patients was not associated with decrease in markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a slightly negative effect.
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[Therapeutic effectiveness of intra-knee-articular injection of platelet-rich plasma on knee articular cartilage degeneration].
Li, M, Zhang, C, Ai, Z, Yuan, T, Feng, Y, Jia, W
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery. 2011;(10):1192-6
Abstract
OBJECTIVE Platelet-rich plasma (PRP) can enhance the chondrocyte proliferation and repair of cartilage defects. To explore the safety and efficacy of intra-knee-articular injection of PRP to treat knee articular cartilage degeneration by comparing with injecting sodium hyaluronate (SH). METHODS Thirty consecutive patients (30 knees) with knee articular cartilage degeneration were selected between January 2010 and June 2010. According to different injections, 30 patients were randomly divided into PRP group (test group, n = 15) and SH group (control group, n = 15). There was no significant difference in gender, age, body mass index, and Kellgren-Lawrence grade between 2 groups (P > 0.05). Test group received 3.5 mL of PRP intra-knee-articular injections while control group received 2 mL of SH during the same time period. Both treatments were administered in series of 3 intra-knee-articular injections at 3-week intervals. Then, adverse reactions were recorded. International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Lequesne index were used for evaluation of treatment results. RESULTS The patients of 2 groups were followed up 6 months. There were significant differences in IKDC score, WOMAC score, and Lequesne index between pre- and post-injection in 2 groups (P < 0.05); no significant difference was found between different time points (3, 4, and 6 months) in test group (P > 0.05), while significant differences were found between the postoperative 6th month and the postoperative 3rd and 4th months in control group (P < 0.05). There was no significant difference in IKDC score, WOMAC score, and Lequesne index between 2 groups within 4 months (P > 0.05), but the effectiveness of test group was significantly better than that of control group at 6 months after injection (P < 0.05). Adverse reactions occurred in 12 patients (31 injections) of test group and in 12 patients (30 injections) of control group. No significant difference in onset time, termination time, and duration of adverse reactions were found between 2 groups (P > 0.05). CONCLUSION Intra-knee-articular injection of PRP to treat knee articular cartilage degeneration is safe, which can alleviate symptoms of pain and swelling and improve the quality of life of patients; however, further data of large samples and long-term follow-up are needed to confirm the safety and effectiveness.