A Quantitative Study of the Effects of High-Dose Parathyroid Hormone (1–34) and Low-Dose rhBMP-2 on Posterolateral Lumbar Spine Fusion in a Rabbit Model

Abstract

Introduction Parathyroid hormone (1–34) (PTH), which is commonly used in the treatment of osteoporosis, has been shown to increase bone mass and reduce the risk of fracture. Previously, we demonstrated that, while intermittent low-dose (10 µg/kg) PTH (1–34) treatment resulted in increased fusion mass volume, it did not improve biomechanical stiffness over the use of autograft alone, and did not improve fusion when combined with BMP-2 treatment (Lina et al, Spine [Phila Pa 1976]. 2014; 39(5):347). However, studies in other rodent models have indicated that the effects of PTH (1–34) on spinal fusion may be dose-dependent (Ming et al, Spine [Phila. Pa. 1976]. 2012; 37(15): 1275; Abe et al, Bone. 2007; 41(5): 775). These rat and mouse studies used PTH (1–34) doses as high as 20 to 40 µg/kg compared with the 10 µg/kg used in our experiments. We thus aim to evaluate whether increasing the dose of PTH (1–34) administered increases both the volume and biomechanical stiffness of the resulting fusion masses and/or exhibits synergistic effects with low-dose BMP-2 treatment. Materials and Methods A total of 60 rabbits underwent posterolateral intertransverse process lumbar spinal fusion surgery, and were assigned to one of the six groups depending upon the fusion grafting group employed: iliac crest autograft alone ( n = 10), iliac crest autograft + 20 µg/kg PTH (1–34) ( n = 10), iliac crest autograft + 40 µg/kg PTH (1–34) ( n = 10), rhBMP-2 alone ( n = 10), rhBMP-2 + 20 µg/kg PTH (1–34) and, rhBMP-2 + 40 µg/kg PTH (1–34). Fusion mass and quality were assessed using manual palpation, CT analysis of fusion mass volume, and four-point nondestructive biomechanical testing. Results/Conclusions: Although manual palpation is used as the standard measure of fusion, we found that CT analysis proved more effective in differentiating fused masses based on bone formation, not fibrous tissue. Both the PTH (1–34) group and BMP-2 increased bone density and volume of the fusion masses. Biomechanical analysis of fusion mass strength is currently underway.