title: Effect of Intermittent Administration of Teriparatide (Parathyroid Hormone 1-34) on Bone Morphogenetic Protein-Induced Bone Formation in a Rat Model of Spinal Fusion.
abstract: 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 μg (control), (2) 2 μg (low dose), or (3) 50 μg (high dose). Each of the rhBMP-2 treatments was studied in combination with intermittent injections of either parathyroid hormone 1-34 (180 μg/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 μg 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-μg and 50-μg 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 hormone 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-induced spinal fusion.
  
  
  CONCLUSIONS
  Our results suggest that the combined administration of rhBMP-2 and parathyroid hormone 1-34 may lead to efficient bone regeneration.
authors.affiliation: Departments of Orthopedic Surgery (T.M., T.K., M.K., M.I., and H.Y.) and Orthopedic Biomaterial Science (Y.M. and T.S.), Graduate School of Medicine, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address for T. Kaito: takashikaito@gmail.com.
authors.forename: Tokimitsu
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Departments of Orthopedic Surgery (T.M., T.K., M.K., M.I., and H.Y.) and Orthopedic Biomaterial Science (Y.M. and T.S.), Graduate School of Medicine, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address for T. Kaito: takashikaito@gmail.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaito
authors.affiliation: Departments of Orthopedic Surgery (T.M., T.K., M.K., M.I., and H.Y.) and Orthopedic Biomaterial Science (Y.M. and T.S.), Graduate School of Medicine, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address for T. Kaito: takashikaito@gmail.com.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kashii
authors.affiliation: Departments of Orthopedic Surgery (T.M., T.K., M.K., M.I., and H.Y.) and Orthopedic Biomaterial Science (Y.M. and T.S.), Graduate School of Medicine, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address for T. Kaito: takashikaito@gmail.com.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Departments of Orthopedic Surgery (T.M., T.K., M.K., M.I., and H.Y.) and Orthopedic Biomaterial Science (Y.M. and T.S.), Graduate School of Medicine, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address for T. Kaito: takashikaito@gmail.com.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Departments of Orthopedic Surgery (T.M., T.K., M.K., M.I., and H.Y.) and Orthopedic Biomaterial Science (Y.M. and T.S.), Graduate School of Medicine, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address for T. Kaito: takashikaito@gmail.com.
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Departments of Orthopedic Surgery (T.M., T.K., M.K., M.I., and H.Y.) and Orthopedic Biomaterial Science (Y.M. and T.S.), Graduate School of Medicine, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address for T. Kaito: takashikaito@gmail.com.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000601:surgery*; D008297:Male; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion; D019379:Teriparatide / Q000008:administration & dosage* / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D019485:Bone Morphogenetic Proteins; D019379:Teriparatide