title: Effect of early full weight-bearing after joint injury on inflammation and cartilage degradation.
abstract: BACKGROUND
  Early full weight-bearing after an acute osteochondral injury avoids problems associated with immobility but may also be harmful by amplifying the inflammatory response. To investigate these effects, we developed an in vivo model of subchondral trauma.
  
  
  METHODS
  After an impact injury to the femoral condyle, fourteen dogs were randomized to immediate full weight-bearing or to four weeks of minimal weight-bearing before full weight-bearing. Synovial fluid was sampled by aspiration at one, two, four, eight, twelve, sixteen, twenty, and twenty-four weeks. Neutrophils, monocytes, and lymphocytes were enumerated, and the concentrations of tumor necrosis factor-alpha, interleukin-10, nitric oxide, matrix metalloproteinases, and glycosaminoglycans were measured.
  
  
  RESULTS
  Compared with the findings for uninjured joints, the synovial fluid from the impacted joints of full-weight-bearing dogs had significantly higher peak concentrations of neutrophils (p = 0.0006 at one week), mononuclear leukocytes (p = 0.001 at four weeks), tumor necrosis factor-alpha (p = 0.001 at one week), nitric oxide (p = 0.001 at one week), matrix metalloproteinases (p = 0.008 at one week), and glycosaminoglycans (p = 0.002 at four weeks and p = 0.001 at six months). The size of the bone bruise correlated with the peak concentrations of tumor necrosis factor-alpha (r2= 0.89, p = 0.007; Spearman rank test), matrix metalloproteinases (r2= 0.96, p = 0.0004), and glycosaminoglycans (r2= 0.96, p = 0.0004). However, restriction to minimal weight-bearing for four weeks after the injury led to a significant reduction in the synovial fluid concentrations of neutrophils (p = 0.007 at one week and p = 0.01 at two weeks), tumor necrosis factor-alpha (p = 0.0006 to 0.02 during the first four weeks), nitric oxide (p = 0.001 to 0.04 during the first four weeks), and matrix metalloproteinases (p = 0.007 to 0.01 from the second week to the eighth week). In contrast, interleukin-10 concentrations were significantly higher (p = 0.002 at one week) and glycosaminoglycan levels remained at normal levels in animals that were restricted from immediate full weight-bearing after the injury.
  
  
  CONCLUSIONS
  The magnitude of the inflammatory response is proportional to the size of the bone bruise. Restriction to minimal weight-bearing for four weeks reduces the magnitude of the inflammatory response and the cartilage degradation following articular cartilage impact injury.
  
  
  CONCLUSIONS
  Strategies to minimize mechanical stress during the early postinjury period may help to preserve cartilage integrity and forestall the development of osteoarthritis.
authors.affiliation: Research Office, MS 151, Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030, USA. dgreen@bcm.tmc.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Green
authors.forename: P C
authors.initials: PC
authors.lastname: Noble
authors.forename: J R
authors.initials: JR
authors.lastname: Bocell
authors.forename: J S
authors.initials: JS
authors.lastname: Ahuero
authors.forename: B A
authors.initials: BA
authors.lastname: Poteet
authors.forename: H H
authors.initials: HH
authors.lastname: Birdsall
mesh_terms: D000818:Animals; D003288:Contusions / Q000534:rehabilitation*; D004195:Disease Models, Animal; D004285:Dogs; D004434:Early Ambulation; D006025:Glycosaminoglycans / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D013264:Stifle / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology*; D013582:Synovial Fluid / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016474:Weight-Bearing
chemical_list: D006025:Glycosaminoglycans; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases