title: Relationships amongst osteoarthritis biomarkers, dynamic knee joint load, and exercise: results from a randomized controlled pilot study.
abstract: BACKGROUND
  Little is known about the relationships of circulating levels of biomarkers of cartilage degradation with biomechanical outcomes relevant to knee osteoarthritis (OA) or biomarker changes following non-pharmacological interventions. The objectives of this exploratory, pilot study were to: 1) examine relationships between biomarkers of articular cartilage degradation and synthesis with measures of knee joint load during walking, and 2) examine changes in these biomarkers following 10 weeks of strengthening exercises.
  
  
  METHODS
  Seventeen (8 male, 9 female; 66.1 +/- 11.3 years of age) individuals with radiographically-confirmed medial tibiofemoral OA participated. All participants underwent a baseline testing session where serum and urine samples were collected, followed by a three-dimensional motion analysis. Motion analysis was used to calculate the external knee adduction moment (KAM) peak value and impulse. Following baseline testing, participants were randomized to either 10 weeks of: 1) physiotherapist-supervised lower limb muscle strengthening exercises, or 2) no exercises (control). Identical follow-up testing was conducted 11 weeks after baseline. Biomarkers included: urinary C-telopeptide of type II collagen (uCTX-II) and type II collagen cleavage neoepitope (uC2C), serum cartilage oligomeric matrix protein (sCOMP), serum hyaluronic acid (sHA) and serum C-propeptide of type II procollagen (sCPII). Linear regression analysis was used to examine relationships between measures of the KAM and biomarker concentrations as baseline, as well as between-group differences following the intervention.
  
  
  RESULTS
  KAM impulse predicted significant variation in uCTX-II levels at baseline (p = 0.04), though not when controlling for disease severity and walking speed (p = 0.33). KAM impulse explained significant variation in the ratio uCTX-II;sCPII even when controlling for additional variables (p = 0.04). Following the intervention, changes in sCOMP were significantly greater in the exercise group compared to controls (p = 0.04). On average those in the control group experienced a slight increase in sCOMP and uCTX-II, while those in the exercise group experienced a reduction. No other significant findings were observed.
  
  
  CONCLUSIONS
  This research provides initial evidence of a potential relationship between uCTX-II and knee joint load measures in patients with medial tibiofemoral knee OA. However, this relationship became non-significant after controlling for disease severity and walking speed, suggesting further research is necessary. It also appears that sCOMP is amenable to change following a strengthening intervention, suggesting a potential beneficial role of exercise on cartilage structure.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01241812.
authors.affiliation: Department of Physical Therapy, University of British Columbia, BC, Vancouver, Canada. michael.hunt@ubc.ca
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hunt
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Pollock
authors.forename: Virginia Byers
authors.initials: VB
authors.lastname: Kraus
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.forename: Sue
authors.initials: S
authors.lastname: Peters
authors.forename: Janet L
authors.initials: JL
authors.lastname: Huebner
authors.forename: Eric C
authors.initials: EC
authors.lastname: Sayre
authors.forename: Jolanda
authors.initials: J
authors.lastname: Cibere
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007719:Knee Joint / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D010865:Pilot Projects; D016037:Single-Blind Method; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D015415:Biomarkers