Effect of intermittent PTH (1-34) on posterolateral spinal fusion with iliac crest bone graft in an ovariectomized rat model

Osteoporos Int. 2013 Oct;24(10):2693-700. doi: 10.1007/s00198-013-2385-7. Epub 2013 Jun 12.

Abstract

Summary: Intermittent treatment with high-dose parathyroid hormone (PTH) enhances the quantity and quality of the fusion callus and reduces healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague-Dawley rats. Intermittent PTH (1-34) could be an appropriate adjunctive therapy for osteoporotic patients undergoing posterolateral intertransverse process fusion.

Introduction: The study was designed to test the hypothesis that intermittent administration of PTH improves spinal fusion rates in a randomized controlled, ovariectomized osteoporotic rat spinal fusion model.

Methods: Thirty-six 10-week-old Sprague-Dawley rats were ovariectomized and underwent bilateral posterolateral L4-L5 spinal fusion with autologous iliac bone graft 6 weeks later. The experimental (PTH) group (18 rats) received daily subcutaneously administered injections of PTH (1-34) at 30 μg/kg/day starting on the day of operation. The control group (18 rats) received a subcutaneously administered injection of normal saline of the same volume. Nine rats from each group were sacrificed at 4 and 6 weeks. After sacrifice, the L4-L5 vertebral segments were removed and analyzed by plain radiographs, μ-CT, histomorphometry, and serum bone metabolism marker.

Results: The PTH group had a significantly higher fusion rate and X-ray fusion score than the control group at 4 and 6 weeks (p < 0.05). μ-CT and histological analysis showed that the fusion bone volume and cortical thickness for the PTH group were significantly higher than those for the control group at 4 and 6 weeks (p < 0.05). Metabolic marker analysis also showed significant difference between the two groups. The serum osteocalcin was significantly higher in the PTH group at 4 and 6 weeks, and levels of N-terminal peptide of type I collagen were significantly higher at 4 weeks (p < 0.05).

Conclusion: Intermittent treatment with high-dose PTH enhances the quantity of the fusion callus and reduces the healing time of posterolateral spinal fusion with autologous iliac bone grafts in ovariectomized osteoporotic female Sprague-Dawley rats.

MeSH terms

  • Animals
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use
  • Bone Regeneration / drug effects*
  • Bone Transplantation / methods*
  • Chemotherapy, Adjuvant
  • Disease Models, Animal
  • Drug Administration Schedule
  • Drug Evaluation, Preclinical / methods
  • Female
  • Ilium / transplantation
  • Injections, Subcutaneous
  • Lumbar Vertebrae / physiopathology
  • Lumbar Vertebrae / surgery
  • Osteoporotic Fractures / drug therapy
  • Osteoporotic Fractures / physiopathology
  • Osteoporotic Fractures / surgery*
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Fractures / drug therapy
  • Spinal Fractures / physiopathology
  • Spinal Fractures / surgery*
  • Spinal Fusion / methods*
  • Teriparatide / administration & dosage
  • Teriparatide / pharmacology*
  • Teriparatide / therapeutic use
  • Wound Healing / drug effects

Substances

  • Bone Density Conservation Agents
  • Teriparatide