The Impact of Weight-bearing Exercise, Non-Weight-bearing Exercise, and Cardiovascular Stress on Biochemical Markers of Cartilage Turnover in Patients With Mild to Moderate Knee Osteoarthritis: A Sequential, Cross-Over, Clinical Study.
Bjerre-Bastos, Jonathan J; Sejersen, Casper; Nielsen, Henning Bayet al.
adrenaline; biochemical markers; exercise; knee osteoarthritis; type II collagen; Immunology and Allergy; Biomedical Engineering; Physical Therapy, Sports Therapy and Rehabilitation
Abstract :
[en] [en] OBJECTIVE: To investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).
DESIGN: This was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured.
RESULTS: Mean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T20min = -12.3%, 95% confidence interval [CI]: -19.3% to -5.2%). PRO-C2 increased during cycling (T10min = 14.0%, 95% CI = 4.1% to 23.8%) and running (T20min = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T50min = -19.9%, 95% CI = -29.2% to -10.6%), running (T50min = -22.8%, 95% CI = -32.1% to -13.5%), and infusion of adrenaline (peak, T50min = -9.8%, 95% CI = -20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T260min = 21.7%, 95% CI = -1.6% to 45.1%).
CONCLUSION: Exercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Bjerre-Bastos, Jonathan J ; Xlab, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark ; NBCD A/S, Herlev, Denmark
Sejersen, Casper; Department of Anaesthesiology, Rigshospitalet, Copenhagen, Denmark ; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Nielsen, Henning Bay; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark ; Department of Anaesthesia and Intensive Care Medicine, Zealand University Hospital, Roskilde, Denmark ; Department of Nutrition, Exercise and Sport, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
Boesen, Mikael; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark ; Department of Radiology, Bispebjerg and Frederiksberg Hospitals, Copenhagen, Denmark
Secher, Niels H; Department of Anaesthesiology, Rigshospitalet, Copenhagen, Denmark ; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Distajo, Gregorio; Prosoft Clinical, Wayne, NJ, USA
Flood, Vincent; Prosoft Clinical, Wayne, NJ, USA
Henrotin, Yves ; Université de Liège - ULiège > Département des Sciences de l'activité physique et de la réadaptation > Pathologie générale et physiopathologie - Techniques particulières de kinésithérapie ; Department of Physical and Rehabilitation, VIVALIA, Marche-en-Famenne, Belgium
Krustrup, Peter; Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
Kitchen, Carl-Christian; Department of Anaesthesiology, Rigshospitalet, Copenhagen, Denmark ; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Thudium, Christian S; Nordic Bioscience, Herlev, Denmark
The Impact of Weight-bearing Exercise, Non-Weight-bearing Exercise, and Cardiovascular Stress on Biochemical Markers of Cartilage Turnover in Patients With Mild to Moderate Knee Osteoarthritis: A Sequential, Cross-Over, Clinical Study.
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.J.B.-B. was funded by the Danish Research Fund, employee at NBCD A/S and of Sanos Clinic A/S. J.R.A. and A.R.B. are employees and shareholders of NBCD A/S. Y.H. is president of Artialis SA. M.U. is employee at Artialis SA. C.S.T. is employee at Nordic Bioscience A/S. CS., N.H.S., H.B.N., M.B., G.D., V.F., P.K., and C.-C.K. have nothing to declare.
Bjerre-Bastos JJ Nielsen HB Andersen JR Karsdal M Bay-Jensen AC Boesen M, et al Does moderate intensity impact exercise and non-impact exercise induce acute changes in collagen biochemical markers related to osteoarthritis?—An exploratory randomized cross-over trial. Osteoarthritis Cartilage. 2021;29(7):986-94. doi:10.1016/j.joca.2021.02.569.
Oo WM Little C Duong V Hunter DJ. The development of disease-modifying therapies for osteoarthritis (DMOADs): the evidence to date. Drug Des Devel Ther. 2021;152921-45. doi:10.2147/DDDT.S295224.
Mobasheri A Henrotin Y. Biomarkers of (osteo)arthritis. Biomarkers. 2015;20(8):513-8. doi:10.3109/1354750X.2016.1140930.
Geenen R Overman CL Christensen R Åsenlöf P Capela S Huisinga KL, et al EULAR recommendations for the health professional’s approach to pain management in inflammatory arthritis and osteoarthritis. Ann Rheum Dis. 2018;77(6):797-807. doi:10.1136/annrheumdis-2017-212662.
Bjerre-Bastos JJ Karsdal MA Boesen M Bliddal H Bay-Jensen A-C Andersen JR, et al The acute and long-term impact of physical activity on biochemical markers and MRI measures in osteoarthritis—Perspectives for clinical osteoarthritis research. Transl Sport Med. 2020;3:384-94. doi:10.1002/tsm2.155.
Vincent TL. Mechanoflammation in osteoarthritis pathogenesis. Semin Arthritis Rheum. 2019;49(3S):S36-8. doi:10.1016/j.semarthrit.2019.09.018.
Bender A Kaesser U Eichner G Bachmann G Steinmeyer J. Biomarkers of hand osteoarthritis are detectable after mechanical exercise. J Clin Med. 2019;8:1545. doi:10.3390/jcm8101545.
Helmark IC Petersen MC Christensen HE Kjaer M Langberg H. Moderate loading of the human osteoarthritic knee joint leads to lowering of intraarticular cartilage oligomeric matrix protein. Rheumatol Int. 2012;32(4):1009-14. doi:10.1007/s00296-010-1716-7.
Bjerre-Bastos JJ Nielsen HB Andersen JR He Y Karsdal M Bay-Jensen AC, et al. Evaluation of serum ARGS neoepitope as an osteoarthritis biomarker using a standardized model for exercise-induced cartilage extra cellular matrix turnover. Osteoarthr Cartil Open. 2020;2(2):100060. doi:10.1016/j.ocarto.2020.100060.
Roos EM Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1:64. doi:10.1186/1477-7525-1-64.
Bay-Jensen AC Liu Q Byrjalsen I Li Y Wang J Pedersen C, et al Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM-Increased serum CIIM in subjects with severe radiographic osteoarthritis. Clin Biochem. 2011;44(5-6):423-9. doi:10.1016/j.clinbiochem.2011.01.001.
Groen SS Sinkeviciute D Bay-Jensen AC Thudium CS Karsdal MA Thomsen SF, et al A serological type II collagen neoepitope biomarker reflects cartilage breakdown in patients with osteoarthritis. Osteoarthr Cartil Open. 2021;3(4):100207. doi:10.1016/j.ocarto.2021.100207.
Deberg M Labasse A Christgau S Cloos P Henriksen D Chapelle JP, et al New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 2005;13(3):258-65. doi:10.1016/j.joca.2004.12.002.
Luo Y He Y Reker D Gudmann NS Henriksen K Simonsen O, et al A novel high sensitivity type II collagen blood-based biomarker, PRO-C2, for assessment of cartilage formation. Int J Mol Sci. 2018;19:3485. doi:10.3390/ijms19113485.
Bay-Jensen AC Hoegh-Madsen S Dam E Henriksen K Sondergaard BC Pastoureau P, et al Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis. Rheumatol Int. 2010;30(4):435-42.
Helmark IC Mikkelsen UR Børglum J Rothe A Petersen MC Andersen O, et al Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial. Arthritis Res Ther. 2010;12(4):ar3064. doi:10.1186/ar3064.
Bihlet AR Byrjalsen I Bay-Jensen AC. Associations between biomarkers of bone and cartilage turnover, gender, pain categories and radiographic severity in knee osteoarthritis. Arthritis Res Ther. 2019;21:203. doi:10.1186/s13075-019-1987-7.
Bihlet AR Bjerre-Bastos JJ Andersen JR Byrjalsen I Karsdal MA Bay-Jensen AC. Clinical and biochemical factors associated with risk of total joint replacement and radiographic progression in osteoarthritis: data from two phase III clinical trials. Semin Arthritis Rheum. 2020;50(6):1374-81. doi:10.1016/j.semarthrit.2020.03.002.
Chu CR Sheth S Erhart-Hledik JC Do B Titchenal MR Andriacchi TP. Mechanically stimulated biomarkers signal cartilage changes over 5 years consistent with disease progression in medial knee osteoarthritis patients. J Orthop Res. 2018;36(3):891-7. doi:10.1002/jor.23720.
Bjerre-Bastos JJ Nielsen HB Andersen JR Karsdal M Boesen M Mackey AL, et al A biomarker perspective on the acute effect of exercise with and without impact on joint tissue turnover: an exploratory randomized cross-over study. Eur J Appl Physiol. 2021;121(10):2799-809. doi:10.1007/s00421-021-04751-z.
Heinemeier KM Schjerling P Heinemeier J Møller MB Krogsgaard MR Grum-Schwensen T, et al Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage. Sci Transl Med. 2016;8:346ra90. doi:10.1126/scitranslmed.aad8335.
Hick AC Malaise M Loeuille D Conrozier T Maugars Y Pelousse F, et al Cartilage biomarkers Coll2-1 and Coll2-1NO2 are associated with knee OA MRI features and are helpful in identifying patients at risk of disease worsening. Cartilage. 2021;13(1 Suppl.):1637S-47. doi:10.1177/19476035211021892.
Liem Y Judge A Kirwan J Ourradi K Li Y Sharif M. Multivariable logistic and linear regression models for identification of clinically useful biomarkers for osteoarthritis. Sci Rep. 2020;10:11328. doi:10.1038/s41598-020-68077-0.
Henrotin Y Labasse A Franck T Bosseloir A Bury T Deberg M. Collagen catabolism through Coll2-1 and Coll2-1NO2 and myeloperoxidase activity in marathon runners. Springerplus. 2013;2(1):92. doi:10.1186/2193-1801-2-92.
Bjerre-Bastos JJ Sejersen C Bihlet AR Secher NH Mackey AL Kitchen CC, et al An estimate of plasma volume changes following moderate-high intensity running and cycling exercise and adrenaline infusion. Front Physiol. 2022;13:948087. doi:10.3389/fphys.2022.948087.
Erhart-Hledik JC Favre J Asay JL Smith RL Giori NJ Mündermann A, et al A relationship between mechanically-induced changes in serum cartilage oligomeric matrix protein (COMP) and changes in cartilage thickness after 5 years. Osteoarthritis Cartilage. 2012;20(11):1309-15. doi:10.1016/j.joca.2012.07.018.
Cattano NM Driban JB Cameron KL Sitler MR. Impact of physical activity and mechanical loading on biomarkers typically used in osteoarthritis assessment: current concepts and knowledge gaps. Ther Adv Musculoskelet Dis. 2017;9(1):11-21. doi:10.1177/1759720X16670613.
