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.
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.
['Holmes|Christina A|CA|', 'Ishida|Wataru|W|', 'Elder|Benjamin D|BD|', 'Lo|Sheng-Fu Larry|SL|', 'Chen|Yunchan Amy|YA|', 'Kim|Edmond|E|', 'Locke|John|J|', 'Taylor|Maritza|M|', 'Witham|Timothy F|TF|']
D000818:Animals D055396:Bone Morphogenetic Protein 2 D019485:Bone Morphogenetic Proteins D016025:Bone Transplantation D007085:Ilium D008159:Lumbar Vertebrae D008161:Lumbosacral Region D008297:Male D023421:Models, Animal D010281:Parathyroid Hormone D011817:Rabbits D013123:Spinal Fusion D014182:Transplantation, Autologous
Parathyroid hormone Rabbit model Spinal fusion Biomechanical testing Bone graft substitute Recombinant human bone morphogenetic protein 2 Volume analysis