title: Repetitive Stresses Generate Osteochondral Lesions in Skeletally Immature Rabbits.
abstract: The origin of juvenile osteochondritis dissecans (OCD) is unknown. Existing experimental animal models of OCD most frequently involve surgically created lesions but do not examine repetitive stress as a possible cause of OCD.
  
  
  
  Repetitive stresses can cause OCD-like lesions in immature animals.
  
  
  
  Controlled laboratory study.
  
  
  
  Six juvenile rabbits were subjected to repetitive loading forces of approximately 160% body weight to the right hindlimb during five 45-minute sessions per week for 5 weeks. The contralateral limb was the unloaded control. After 5 weeks, rabbits were euthanized and examined with radiographs, micro-computed tomography, and gross and histopathologic analysis.
  
  
  
  All 6 rabbits developed osteochondral lesions in loaded limbs on the medial and lateral femoral condyles, while contralateral unloaded limbs did not demonstrate lesions. Loaded limbs developed relative osteopenia in the femoral epiphysis and tibial metaphysis with associated decreased trabecular density. Loaded limbs also demonstrated increased femoral subchondral bone thickness near the lesions. Lesions did not have grossly apparent extensive articular cartilage damage; however, cartilage thickness increased on histology with reduced ossification. Loaded knees demonstrated abundant chondrocyte cloning, limited cartilage fissuring, and a focal loss of cellularity at the articular surface.
  
  
  
  Low-grade lesions in human OCD have little gross articular cartilage involvement despite substantial changes to the subchondral bone as shown on magnetic resonance imaging and radiographs. Histopathology findings in this study included cartilage thickening and chondrocyte cloning resembling those of recently published human OCD biopsy studies. Our animal model supports the hypothesis that repetitive stress to immature knees may contribute to the development of human OCD. This model may be useful in understanding the pathophysiology and healing of human OCD.
  
  
  
  Repetitive physiologic stress generated changes to the subchondral bone in immature animals without causing extensive articular damage. The similarities of these lesions in gross and histologic appearance with human OCD support repetitive stress as the likely the cause for human OCD.
authors.affiliation: Department of Orthopaedic Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA austinvstonemd@gmail.com.
authors.forename: Austin V
authors.initials: AV
authors.lastname: Stone
authors.affiliation: Department of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Little
authors.affiliation: Department of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Glos
authors.affiliation: Department of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Keith F
authors.initials: KF
authors.lastname: Stringer
authors.affiliation: Department of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wall
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D012090:Cumulative Trauma Disorders / Q000473:pathology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000000981:diagnostic imaging / Q000473:pathology*; D010008:Osteochondritis Dissecans / Q000000981:diagnostic imaging / Q000473:pathology*; D011817:Rabbits; D011859:Radiography; D055114:X-Ray Microtomography
keywords: cartilage; juvenile osteochondritis dissecans; osteochondral; osteochondritis dissecans; subchondral bone