The Effects of High-Dose Parathyroid Hormone Treatment on Fusion Outcomes in a Rabbit Model of Posterolateral Lumbar Spinal Fusion Alone and in Combination with Bone Morphogenetic Protein 2 Treatment

World Neurosurg. 2018 Jul:115:e366-e374. doi: 10.1016/j.wneu.2018.04.058. Epub 2018 Apr 17.

Abstract

Background: Parathyroid hormone (PTH) (1-34) treatment reduces fracture risk in osteoporotic patients. Previously, we demonstrated in a rabbit model that low-dose PTH treatment resulted in increased fusion mass volume. As effects of PTH on bone are dose-dependent, we aimed to evaluate whether increasing dosage of PTH increases both volume and biomechanical stiffness of the resulting fusion masses and/or exhibits synergistic effects with low-dose bone morphogenetic protein 2 (BMP-2).

Methods: Posterolateral lumbar spinal fusion surgery was performed on 60 New Zealand White rabbits divided into 6 experimental groups: iliac crest autograft alone, autograft plus 20 μg/kg/day PTH, autograft plus 40 μg/kg/day PTH, BMP-2 alone, BMP-2 plus 20 μg/kg/day PTH, and BMP-2 plus 40 μg/kg PTH. Fusion was assessed at postoperative week 6 via manual palpation, volumetric computed tomography analysis, and 4-point bending biomechanical testing.

Results: All groups treated with BMP-2 fused. Increasing doses of PTH resulted in increased fusion mass volume compared with autograft alone. Autograft plus 40 μg/kg/day PTH yielded fusion mass volumes comparable to BMP-2. When the autograft groups were considered alone, increased mechanical stiffness was observed only in the 20 μg/kg/day group. No significant stiffness differences were observed between BMP-2 groups.

Conclusions: Treatment with the highest dose of PTH resulted in fusion mass volumes similar to those obtained with BMP-2. When the autograft groups were considered alone, significant increases in mechanical stiffness were observed at a dosage of 20 μg/kg/day, suggesting there may be an optimal dose of PTH in the rabbit model. Effects of BMP-2 on fusion were dominant.

Keywords: Biomechanical testing; Bone graft substitute; Parathyroid hormone; Rabbit model; Recombinant human bone morphogenetic protein 2; Spinal fusion; Volume analysis.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Morphogenetic Proteins / therapeutic use
  • Bone Transplantation / methods
  • Ilium / drug effects
  • Ilium / transplantation*
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / surgery*
  • Lumbosacral Region / diagnostic imaging
  • Male
  • Models, Animal
  • Parathyroid Hormone / pharmacology*
  • Rabbits
  • Spinal Fusion / methods
  • Transplantation, Autologous / methods

Substances

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Parathyroid Hormone