title: Longterm effects of intraarticular hyaluronan on synovial fluid in osteoarthritis of the knee.
abstract: OBJECTIVE
  Intraarticular (IA) hylan injections constitute second-line therapy for osteoarthritis (OA) of the knee, but human studies suggesting a possible mechanism of action are lacking. We examined the effect of IA Hylan GF-20 injections on synovial fluid (SF) hyaluronan (HA) concentration, viscosity, and elasticity over a 6-month period in patients with mild to moderate OA of the knees.
  
  
  METHODS
  Patients with symptomatic knee OA (Osteoarthritis Research Society International grade 1-2) had SF aspirated from the study knee pre- and 3 and 6 months post-Hylan injection. Primary endpoints included SF HA concentration, viscosity, and elasticity. SF HA concentration was determined using uronic acid assay, and rheology measured using a micro-Fourier rheometer.
  
  
  RESULTS
  Sequential SF samples were available from 32 of 60 subjects injected at baseline (15 men, 17 women; mean age 65 yrs) at 3 months post-injection. The mean HA concentration had increased by 13% (p<0.0008), and the complex shear modulus had increased by 16% (p<0.03). Sufficient SF was also available from 19 of these subjects at 6 months post-injection when mean HA concentration was 2.24+/-0.62 mg/ml compared to their baseline mean of 2.02+/-0.52 mg/ml, an increase of 10% (p<0.053).
  
  
  CONCLUSIONS
  This open-label study showed a statistically significant change from baseline in both SF HA concentration and complex shear modulus at 3 months following IA Hylan GF-20 injection among subjects with mild to moderate knee OA. These results suggest that one possible mechanism of action of viscosupplementation is to promote endogenous HA production. Longer-term studies are required to identify whether these changes in SF measures are important for modification of disease progression in knee OA.
authors.affiliation: University of Sydney Institute of Bone and Joint Research, Royal North Shore Hospital, St. Leonards, NSW, Australia.
authors.forename: Hanish
authors.initials: H
authors.lastname: Bagga
authors.forename: Daniel
authors.initials: D
authors.lastname: Burkhardt
authors.forename: Philip
authors.initials: P
authors.lastname: Sambrook
authors.forename: Lyn
authors.initials: L
authors.lastname: March
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004548:Elasticity / Q000187:drug effects; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013582:Synovial Fluid / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D014574:Uronic Acids / Q000032:analysis
chemical_list: D014574:Uronic Acids; D006820:Hyaluronic Acid