Quantitative study of parathyroid hormone (1-34) and bone morphogenetic protein-2 on spinal fusion outcomes in a rabbit model of lumbar dorsolateral intertransverse process arthrodesis

Spine (Phila Pa 1976). 2014 Mar 1;39(5):347-55. doi: 10.1097/BRS.0000000000000169.

Abstract

Study design: A posterolateral rabbit spinal fusion model was used to evaluate the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and teriparatide (PTH [1-34]) used individually and in combination on spinal fusion outcomes.

Objective: To test the efficacy of parathyroid hormone on improving spinal fusion outcomes when used with BMP-2.

Summary of background data: Of the more than 250,000 spinal fusion surgical procedures performed each year, 5% to 35% of these will result in pseudarthrosis. Growing controversy on the efficacy and cost of rhBMP-2 for improving spinal fusion outcomes has presented a challenge for clinicians. Research into PTH as an adjunct therapy to rhBMP-2 for spinal fusion has not yet been investigated.

Methods: Forty-eight male New Zealand white rabbits underwent bilateral posterolateral intertransverse process arthrodesis surgery at the L5-L6 level. Animals were divided into 6 groups. Two groups were treated with autograft alone or autograft and PTH (1-34), whereas the other 4 groups were treated with low-dose rhBMP-2 alone, high-dose rhBMP-2 alone, or either dose combined with PTH (1-34). All animals were euthanized 6 weeks after surgery. The L4-L7 spinal segment was removed and assessed using manual palpation, computed tomography (CT), and biomechanical testing.

Results: CT assessments revealed fusion in 50% of autograft controls, 75% of autograft PTH (1-34) animals, 87.5% in the 2 groups treated with low-dose rhBMP-2, and 100% in the 2 groups treated with high-dose rhBMP-2. CT volumetric analysis demonstrated that all groups treated with biologics had fusion masses that were on average significantly larger than those observed in the control group (P < 0.0001). Biomechanical data demonstrated no statistical difference between controls, PTH (1-34), and low-dose rhBMP-2 in any testing orientation. PTH (1-34) did not increase bending stiffness when used adjunctively with either low-dose or high-dose rhBMP-2.

Conclusion: Although intermittent teriparatide administration results in increased fusion mass volume, it does not improve biomechnical stiffness over use of autograft alone. When delivered concurrently with high- and low-dose rhBMP-2, teriparatide provided no statistically significant improvement in biomechanical stiffness.

Level of evidence: N/A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Bone Transplantation / methods
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Follow-Up Studies
  • Humans
  • Lumbar Vertebrae / surgery*
  • Male
  • Parathyroid Hormone / therapeutic use*
  • Rabbits
  • Recombinant Proteins / therapeutic use
  • Spinal Fusion / methods*
  • Transforming Growth Factor beta / therapeutic use*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Bone Morphogenetic Protein 2
  • Parathyroid Hormone
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2