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
A posterolateral lumbar spinal fusion model was used in rabbits to evaluate the effects of recombinant human bone morphogenetic protein-2 and teriparatide (parathyroid hormone [1–34]) on spinal fusion outcomes. Fusion characteristics were assessed using manual palpation, computed tomographic volumetric analysis, and 4-point bending biomechanical testing.
From the Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Address correspondence and reprint requests to Timothy F. Witham, MD, Department of Neurosurgery, The Johns Hopkins Hospital, 600 North Wolfe St, Meyer 7-109, Baltimore, MD 21287; E-mail: email@example.com
Acknowledgment date: August 8, 2013. First revision date: December 6, 2013. Acceptance date: December 9, 2013.
The device(s)/drug(s) that is/are the subject of this manuscript is/are exempt from FDA or corresponding national regulations because: They were used in an animal model where such regulations are not applicable. Current use of recombinant human bone morphogenetic protein-2 in the clinic is FDA-approved for lumbar spinal fusion surgery. This is functionally analogous to the posterolateral intertransverse arthrodesis procedure that is used in our rabbit model. On the contrary, parathyroid hormone (PTH) (1-34), although FDA-approved for the treatment of patients with osteoporosis, has been used in the literature for similar New Zealand White rabbit spinal fusion models. Concurrently, FDA regulations do not apply to this model. The manuscript includes unlabeled/investigational uses of the products/devices listed below and the status of these is disclosed in the manuscript: teriparatide is approved for use in the treatment of osteoporosis. In this study, we investigate its use in spinal fusion in an animal model.
Eli Lilly Pharmaceuticals, The Johns Hopkins Neurological Pain Research Institute, The Gordon and Marilyn Macklin Foundation funds were received to support this work.
Relevant financial activities outside the submitted work: board membership, consultancy, grants/grants pending, stock/stock options, travel/accommodations/meeting expenses and grants.