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A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis.

Publication ,  Journal Article
Luo, Y; Samuels, J; Krasnokutsky, S; Byrjalsen, I; Kraus, VB; He, Y; Karsdal, MA; Abramson, SB; Attur, M; Bay-Jensen, AC
Published in: J Orthop Traumatol
March 9, 2021

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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Published In

J Orthop Traumatol

DOI

EISSN

1590-9999

Publication Date

March 9, 2021

Volume

22

Issue

1

Start / End Page

10

Location

Italy

Related Subject Headings

  • Radiography
  • Predictive Value of Tests
  • Osteoarthritis, Knee
  • Orthopedics
  • Middle Aged
  • Male
  • Humans
  • Female
  • Disease Progression
  • Collagen Type II
 

Citation

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Luo, Y., Samuels, J., Krasnokutsky, S., Byrjalsen, I., Kraus, V. B., He, Y., … Bay-Jensen, A. C. (2021). A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis. J Orthop Traumatol, 22(1), 10. https://doi.org/10.1186/s10195-021-00572-0
Luo, Yunyun, Jonathan Samuels, Svetlana Krasnokutsky, Inger Byrjalsen, Virginia B. Kraus, Yi He, Morten A. Karsdal, Steven B. Abramson, Mukundan Attur, and Anne C. Bay-Jensen. “A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis.J Orthop Traumatol 22, no. 1 (March 9, 2021): 10. https://doi.org/10.1186/s10195-021-00572-0.
Luo Y, Samuels J, Krasnokutsky S, Byrjalsen I, Kraus VB, He Y, et al. A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis. J Orthop Traumatol. 2021 Mar 9;22(1):10.
Luo, Yunyun, et al. “A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis.J Orthop Traumatol, vol. 22, no. 1, Mar. 2021, p. 10. Pubmed, doi:10.1186/s10195-021-00572-0.
Luo Y, Samuels J, Krasnokutsky S, Byrjalsen I, Kraus VB, He Y, Karsdal MA, Abramson SB, Attur M, Bay-Jensen AC. A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis. J Orthop Traumatol. 2021 Mar 9;22(1):10.
Journal cover image

Published In

J Orthop Traumatol

DOI

EISSN

1590-9999

Publication Date

March 9, 2021

Volume

22

Issue

1

Start / End Page

10

Location

Italy

Related Subject Headings

  • Radiography
  • Predictive Value of Tests
  • Osteoarthritis, Knee
  • Orthopedics
  • Middle Aged
  • Male
  • Humans
  • Female
  • Disease Progression
  • Collagen Type II