Effect of chondroitin sulfate on soluble biomarkers of osteoarthritis: a method to analyze and interpret the results from an open-label trial in unilateral knee osteoarthritis patients

BMC Musculoskelet Disord. 2016 Oct 6;17(1):416. doi: 10.1186/s12891-016-1268-4.

Abstract

Background: The aim of this study was to investigate the effects of chondroitin sulfate (CS) on the serum levels of Coll2-1 in patients with knee OA.

Methods: Seventy two patients with unilateral symptomatic knee OA were involved in a post-authorization open-label study evaluating CS (800 mg/day). The primary outcome was the % relative change in serum Coll2-1 (sColl2-1). The secondary outcomes were the evaluation of pain (VAS) and function (Lequesne's Index). Responders and non-responders were classified according to OMERACT-OARSI recommendations. Finally, an original cut-off method was applied to categorize patients and interpret individual variations in serum levels of Coll2-1.

Results: Patients showed no difference in the sColl2-1 levels at baseline. When considering responders and non-responders from the ITT population, a significant difference was found for Coll2-1 at 3 months (p = 0.030) and 6 months (p = 0.038). A decrease in pain (VAS) and an improvement in function (LI) were recorded throughout the visits (p < 0.01). Considering an intra-batch cut-off of 21 %, CS decreased Coll2-1 serum levels between baseline and 1-month visit compared to the value of Coll2-1 before treatment (screening visit) which can be interpreted as a drastic reduction of the proportion of patients with an increase of Coll2-1 over 21 % (reduction from 13 to 3 %). It also consisted in a more important proportion of patients with a decrease in Coll2-1 (from 5 to 10 %).

Conclusion: This study proposes a new approach for the analysis and the interpretation of the individual variation in biomarker levels and introduces the notion of metabolic responders.

Trial registration: ID ISRCTN63795830 . The trial was retrospectively registered on 2 October, 2015.

Keywords: Biomarkers; Cartilage metabolism; Chondroitin sulfate; Osteoarthritis; Pain.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Chondroitin Sulfates / administration & dosage
  • Chondroitin Sulfates / therapeutic use*
  • Collagen Type II / blood*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / blood*
  • Osteoarthritis, Knee / drug therapy*
  • Pain Management / methods*
  • Pain Measurement
  • Peptide Fragments / blood*
  • Prospective Studies
  • Treatment Outcome

Substances

  • Biomarkers
  • Collagen Type II
  • Peptide Fragments
  • collagen type II (108-116)
  • Chondroitin Sulfates

Associated data

  • ISRCTN/ISRCTN63795830