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Study · Non-randomized trial · 2021

2 results

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 Traumatology9 Mar 2021Cited by 24 (Europe PMC)

PMID33687578 (opens in a new tab)PMCIDPMC7943687 (opens in a new tab)DOI10.1186/s10195-021-00572-0 (opens in a new tab)PepBankPUB-33687578
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Summary

BackgroundOsteoarthritis (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 methodsThe 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.ResultsIn 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).ConclusionSerum/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 evidenceLevel III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. 2 results from people.

  1. 01HumanNon-randomized trialEfficacy outcome

    In knee osteoarthritis patients, sCT did not significantly affect joint space narrowing versus placebo before PRO-C2 stratification.

    In plain wordsIn knee osteoarthritis patients, sCT did not significantly affect joint space narrowing compared with placebo before PRO-C2 stratification.

    Peptide
    Calcitonin-salmon
    Outcome
    No significant changeJoint space narrowing
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    Dose not stated · oral · 2 yearsAs given in this study (human).

    Source sentences

    Summary
    There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2.
    1 context sentence
    Summary · context
    Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.
  2. 02HumanObservational studyEfficacy outcome

    Among knee OA patients receiving sCT, very low/low PRO-C2 was associated with proportionately fewer progressors than moderate/high PRO-C2 (Chi squared = 6.5, p = 0.011).

    In plain wordsAmong knee OA patients receiving sCT, very low/low PRO-C2 was linked to proportionately fewer progressors than moderate/high PRO-C2.

    Peptide
    Calcitonin-salmon
    Outcome
    DecreaseProgressors by PRO-C2 subgroup
    Study

    n: not reported in source

    Comparator
    Moderate/high PRO-C2 group in the sCT arm
    Analysis
    Exploratory
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Chi squared
    6.5
    PRO-C2 subgroup comparison
    p
    0.011
    PRO-C2 subgroup comparison

    Source sentences

    Summary
    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).
    1 context sentence
    Summary · context
    Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:35 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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