title: Intermittent administration of teriparatide enhances graft bone healing and accelerates spinal fusion in rats with glucocorticoid-induced osteoporosis.
abstract: BACKGROUND
  There has been no study regarding the effect of intermittent administration of teriparatide (TPTD [recombinant human parathyroid hormone (1-34)]) on spinal fusion in patients with glucocorticoid-induced osteoporosis (GIOP).
  
  
  OBJECTIVE
  To elucidate the effect of intermittent administration of TPTD on spinal fusion in rats with GIOP.
  
  
  METHODS
  An experimental animal study of rats under continuous glucocorticoid (GC) exposure undergoing spinal fusion surgery and administration of TPTD or saline.
  
  
  METHODS
  Male 8-week-old rats (n=18) were administered 5 mg/kg methylprednisolone (MP) for 12 weeks. After 6 weeks of MP administration, the rats underwent posterolateral spinal fusion (L4-L5) with iliac crest autograft. Then, five times a week, they were given either saline or 40 μg/kg TPTD for 6 weeks. The following assessments were performed: time-course bone microstructural analysis of the fusion mass and adjacent vertebrae (L6), with in vivo microcomputed tomography (μCT); fusion assessment, with manual palpation testing and three-dimensional CT images; and bone histomorphometrical analysis of the fusion mass.
  
  
  RESULTS
  In the TPTD group, values for bone volume and other bone microstructural parameters at the fusion mass increased and peaked 4 weeks after surgery, and these values were significantly greater than those for the control (CNT) group at 4 and 6 weeks after surgery. Fusion assessment showed that fusion rate was higher in the TPTD group than in the CNT group (CNT group: 56%, TPTD group: 89%). Bone histomorphometry revealed that values for bone formation parameters were significantly higher in the TPTD group than in the CNT group.
  
  
  CONCLUSIONS
  Under continuous GC exposure in a rat model of spinal fusion, intermittent TPTD administration accelerated bone modeling and remodeling predominantly by stimulating bone formation at the fusion mass and increasing the fusion rate. Intermittent TPTD administration also improved bone microarchitecture of adjacent vertebrae.
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: mkashii-osk@umin.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kashii
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tokimitsu
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Honda
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaito
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016025:Bone Transplantation / Q000379:methods*; D005938:Glucocorticoids; D008159:Lumbar Vertebrae / Q000601:surgery*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy / Q000601:surgery*; D010281:Parathyroid Hormone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion / Q000379:methods*; D019379:Teriparatide / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects
chemical_list: D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; C470125:PTH protein, human; D010281:Parathyroid Hormone; D019379:Teriparatide
keywords: Adjacent vertebrae; Bone graft; Bone remodeling; Glucocorticoid-induced osteoporosis; Spinal fusion; Teriparatide