Effect of Intermittent Administration of Teriparatide (Parathyroid Hormone 1-34) on Bone Morphogenetic Protein-Induced Bone Formation in a Rat Model of Spinal Fusion

摘要

Background: Although clinical bone morphogenetic protein (BMP) therapy Is effective at enhancing bone formation In patients managed with spinal arthrodesis, the required doses are very high. Teriparatide (parathyroid hormone 1-34) Is approved by the U.S. Food and Drug Administration to treat osteoporosis and Is a potent anabolic agent. In this study, Intermittent administration of parathyroid hormone 1-34 combined with transplantation of BMP was performed to elucidate the effect of parathyroid hormone 1-34 on the fusion rate and quality of newly formed bone In a rat model. Methods: A total of forty-eight male Sprague-Dawley rats underwent posterolateral lumbar spinal arthrodesis with one of three different treatments with recombinant human (rh) BMP-2: (1) 0 mug (control), (2) 2 mug (low dose), or (3) 50 mug (high dose). Each of the rhBMP-2 treatments was studied In combination with Intermittent Injections of either parathyroid hormone 1-34 (180 mug/kg/wk) or saline solution starting two weeks before the operation and continuing until six weeks after the operation. Osseous fusion was assessed with use of radiographs and a manual palpation test. MIcrostructural indices of the newly formed bone were evaluated with use of micro-computed tomography. The serum markers of bone metabolism were also quantified. Results: The fusion rate In the group treated with 2 mug of rhBMP-2 significantly Increased (from 57% to 100%) with the administration of parathyroid hormone 1-34 (p < 0.05). The fusion rates In the other groups did not change significantly with the administration of parathyroid hormone 1-34. The bone volume density of the newly formed bone significantly increased In both the 2-mug and 50-mug rhBMP-2 treatment groups with the administration of parathyroid hormone 1-34 (p < 0.01). Micro-computed tomography scans of the newly formed bone clearly demonstrated an abundance of trabecular bone formation In the group treated with parathyroid honnone 1-34. In addition, serum levels of osteocalcin were significantly Increased In the parathyroid hormone 1-34 treatment group. Conclusions: Intermittent administration of parathyroid hormone 1-34 significantly Increased fusion rates In the group treated with low-dose rhBMP-2, and It Improved the quality of the newly formed bone In both the high and low-dose groups In a rat model of rhBMP-2-lnduced spinal fusion. Clinical Relevance: Our results suggest that the combined administration of rhBMP-2 and parathyroid hormone 1-34 may lead to efficient bone regeneration.