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A biomarker perspective on the acute effect of exercise with and without impact on joint tissue turnover: an exploratory randomized cross-over study



To investigate acute changes in biochemical markers of bone and cartilage turnover in response to moderate intensity exercise with and without joint impact in healthy human subjects.


A randomized, cross-over, exploratory, clinical study was conducted. Twenty healthy subjects with no history of joint trauma completed 30 min interventions of standardized moderate intensity cycling and running as well as a resting intervention 1 week apart. Blood samples were taken immediately before, four times after exercise and again the next day. Urine was sampled, before, after and the next day. On the day of rest, samples were taken at timepoints similar to the days of exercise. Markers of type I (CTX-I), II (C2M, CTX-II) and VI (C6M) collagen degradation, cartilage oligomeric matrix protein (COMP) and procollagen C-2 (PRO-C2) was measured. Trial registration number: NCT04542655, 02 September 2020, retrospectively registered.


CTX-I was different from cycling (4.2%, 95%CI: 0.4–8.0%, p = 0.03) and resting (6.8%, 95%CI: 2.9–10.7%, p = 0.001) after running and the mean change in COMP was different from cycling (10.3%, 95%CI: 1.1–19.5%, p = 0.03), but not from resting (8.6%, 95%CI: − 0.7–17.8%, p = 0.07) after running. Overall, changes in other biomarkers were not different between interventions.


In this exploratory study, running, but not cycling, at a moderate intensity and duration induced acute changes in biomarkers of bone and cartilage extra-cellular matrix turnover.

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Body mass index


Coefficient of variation


Cartilage oligomeric matrix protein


C-terminal telopeptide of type I collagen


C-terminal telopeptide of type II collagen


MMP-generated fragment of type II collagen


MMP-generated fragment of type VI collagen


Enzyme-linked immunosorbent assays


Intraclass correlation


Knee injury and osteoarthritis outcome score


Lower limit og quantification


Matrix metalloproteinase


Magnetic resonance imaging




Procollagen type II




Standard error of the mean


Upper limit of quantification


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The authors thank Heidi Rønberg for lab assistance, Melanie Kurell and Sarah á Rogvi for clinical assistance and Dr. Kamilla Mundbjerg for technical support.


This study was funded by Nordic Bioscience Clinical Development and the Danish Research Fund.

Author information




JJB, ARB, JRA and HBN designed the protocol. JJB and MB acquired the clinical data. JJB, ARB, and IB conducted the data analysis. JJB, ARB, MK, CT and ALM interpreted the data. JJB drafted the manuscript. Critical revision and approval of the final manuscript was done by all of the authors.

Corresponding author

Correspondence to Jonathan J. Bjerre-Bastos.

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Conflicts of interest

JJB received funding from Nordic Bioscience Clinical Development and the Danish Research Fund. IB and CT are full-time employees of Nordic Bioscience. JRA, MK and ARB are full-time employees and shareholders of Nordic Bioscience. MB and ALM have no conflict of interest.

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Bjerre-Bastos, J.J., Nielsen, H.B., Andersen, J.R. 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 121, 2799–2809 (2021).

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  • Biomarker
  • Exercise
  • Joint
  • Bone
  • Collagen