title: 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.
abstract: METHODS
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  N/A.
authors.affiliation: From the Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ioan A
authors.initials: IA
authors.lastname: Lina
authors.forename: Varun
authors.initials: V
authors.lastname: Puvanesarajah
authors.forename: Jason A
authors.initials: JA
authors.lastname: Liauw
authors.forename: Sheng-fu L
authors.initials: SF
authors.lastname: Lo
authors.forename: David R
authors.initials: DR
authors.lastname: Santiago-Dieppa
authors.forename: Lee
authors.initials: L
authors.lastname: Hwang
authors.forename: Annie
authors.initials: A
authors.lastname: Mao
authors.forename: Ali
authors.initials: A
authors.lastname: Bydon
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Wolinsky
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sciubba
authors.forename: Ziya
authors.initials: Z
authors.lastname: Gokaslan
authors.forename: Christina
authors.initials: C
authors.lastname: Holmes
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Witham
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D016025:Bone Transplantation / Q000379:methods; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D008159:Lumbar Vertebrae / Q000601:surgery*; D008297:Male; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D055396:Bone Morphogenetic Protein 2; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2