High-grade slippage of the lumbar spine in a rat model of spondylolisthesis: effects of cyclooxygenase-2 inhibitor on its deformity

Spine (Phila Pa 1976). 2006 Jul 15;31(16):E528-34. doi: 10.1097/01.brs.0000225974.92243.af.

Abstract

Study design: Radiographic and histologic evaluation of spondylolisthesis in a rat model.

Objectives: To investigate the effects of etodolac, a cox-2 inhibitor, on the severity of spondylolisthesis in a 4-week-old rat model.

Summary of background data: Spondylolisthesis occurs associated with spondylolysis in some pediatric patients. In such patients, the percent of forward slippage varies individually ranging between 0% and 100%. The factors determining the severity of forward slippage have not been clarified as yet. In earlier studies, we found that growth plate stress fracture was the basic lesion and that slippage was a consequence of the stress fracture. Hence, we hypothesized that the capacity of bone healing might be an important determinant of the degree of forward slippage.

Methods: A lumbar spine slippage model was prepared in 4-week-old rats with vertebral physis fracture. To disrupt the fracture healing, the cyclooxygenase-2 (cox-2) inhibitor etodolac was used, and its effects on slippage and deformity were evaluated radiologically and histologically.

Results: In the etodolac group, forward slip significantly increased (P < 0.05) to the Meyerding Grade III while in the control rats it was Grade I or II. Bone remodeling of the vertebral body was suppressed by etodolac. Histologically, epiphyseal separation with slippage was observed in all the control and etodolac-treated rats. However, in the etodolac-treated group, the epiphyseal plate was greatly separated and did not present periosteal thickening at the physis fracture site.

Conclusion: Vertebral forward slippage occurred in young rats after epiphyseal separation. In the etodolac group, slippage increased as deterioration of the bone healing capacity increased. Poor bony healing is suggested as one of the determinants of high-grade spondylolisthesis in children and adolescents.

MeSH terms

  • Animals
  • Bone Remodeling / drug effects
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Etodolac / administration & dosage
  • Etodolac / pharmacology
  • Female
  • Growth Plate / diagnostic imaging
  • Growth Plate / pathology
  • Lumbar Vertebrae / diagnostic imaging*
  • Lumbar Vertebrae / injuries
  • Lumbar Vertebrae / pathology*
  • Radiography
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Spinal Fractures / complications
  • Spinal Fractures / physiopathology
  • Spondylolisthesis / diagnostic imaging*
  • Spondylolisthesis / etiology
  • Spondylolisthesis / pathology*
  • Wound Healing / drug effects

Substances

  • Cyclooxygenase 2 Inhibitors
  • Etodolac