Optimal Intermittent Administration Interval of Parathyroid Hormone 1-34 for Bone Morphogenetic Protein-induced Bone Formation in a Rat Spinal Fusion Model

Abstract

Background: Both bone morphogenetic protein 2 (BMP-2) and teriparatide (parathyroid hormone [PTH] 1-34) are used to enhance bone healing. There is still no established opinion regarding the optimum dose and administration method. We investigated the optimal dose and administration method for the combination of BMP-2 and PTH 1-34 in a rat spinal fusion model. Methods: Group I was implanted with a control carrier. Groups II, III, and IV were implanted with a carrier containing 3μg of recombinant human BMP-2 (rhBMP-2). In addition, following implantation, PTH 1-34 injections were administered to Group III thrice a week (total, 180 μg/kg/week) and Group IV six times a week (total, 180 µg/kg/week). The rats were euthanized after 8 weeks, and their spines were explanted; assessed by manual palpation, radiographs, and high-resolution micro-computed tomography (micro-CT); and subjected to histological analysis. Serum markers of bone metabolism were also analyzed. Results: Manual palpation tests showed that the fusion rates in Groups III and IV were considerably higher than those in Group I. They also had higher radiographic scores than Group I. Micro-CT analysis revealed enhanced bone marrow density expressed as bone volume/tissue volume in Group IV versus Group I. Serum marker analysis revealed that Group IV had higher osteocalcin and lower tartrate-resistant acid phosphatase-5b than Group III. Histological analysis indicated that Group IV had enhanced remodeling. Conclusions: The rhBMP-2 and PTH combination enhanced bone fusion and remodeling of newly formed bone in the rat spinal fusion model. More frequent administration may be superior in terms of bone fusion and bone metabolism.