title: Comparative study of the effect of PTH (1-84) and strontium ranelate in an experimental model of atrophic nonunion.
abstract: This study aimed to set up an experimental model of long bone atrophic nonunion and to explore the potential role of PTH-1-84 (PTH 1-84) and strontium ranelate (SrR). A model of atrophic nonunion was created in Sprague-Dawley rats at the femoral midshaft level. The animals were randomised into four groups. Group A1: control rodents, fracture without bone gap; Group A2: rodents with subtraction osteotomy (non-union model control) treated with saline; Group B: rodents with subtraction osteotomy treated with human-PTH (PTH 1-84); and Group C: rodents with subtraction osteotomy treated with strontium ranelate (SrR). The groups were followed for 12 weeks. X-rays were be obtained at weeks 1, 6 and 12. After sacrificing the animals, we proceeded to the biomechanical study and four point bending tests to evaluate the resistance of the callus and histological study. In second phase, the expression of genes related to osteoblast function was analysed by reverse transcription-quantitative PCR in rats subjected to substraction osteotomy and treated for 2 weeks. The animals were randomised into three groups: Group A2: rodents treated with saline; Group B: rodents treated with PTH 1-84 and Group C: rodents treated with SrR.
  
  
  RESULTS
  No significant histological differences were found between animals subjected to subtraction osteotomy and treated with either saline or PTH (p=0.628), but significant difference existed between animals receiving saline or SrR (p=0.005). There were no significant differences in X-ray score between the saline and PTH groups at either 6 or 12 weeks (p=0.33 and 0.36, respectively). On the other hand, better X-ray scores were found in the SrR group (p=0.047 and 0.006 in comparison with saline, at 6 and 12 weeks, respectively). In line with this, biomechanical tests revealed improved results in the SrR group. Gene expression analysis revealed a slightly decreased levels of DKK1, a Wnt pathway inhibitor, in rats treated with SrR.
  
  
  CONCLUSIONS
  SrR increases has a beneficial effect in this atrophic non-union model in rats. This suggests that it might have a role may have important implications for the potential clinical role in the treatment of fracture nonunion.
authors.affiliation: Department of Traumatology and Orthopedic Surgery, Faculty of Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Cardenal Herrera Oria, s/n 39011, Spain. Electronic address: perezmi@unican.es.
authors.forename: M I
authors.initials: MI
authors.lastname: Pérez Núñez
authors.affiliation: LADICIM-University of Cantabria, E.T.S. Ingenieros de Caminos, Canales y Puertos, Av/Los Castros, s/n 39005, Santander, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Ferreño Blanco
authors.affiliation: Department of Traumatology and Orthopedic Surgery, Faculty of Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Cardenal Herrera Oria, s/n 39011, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Alfonso Fernández
authors.affiliation: LADICIM-University of Cantabria, E.T.S. Ingenieros de Caminos, Canales y Puertos, Av/Los Castros, s/n 39005, Santander, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Casado de Prado
authors.affiliation: Department of Traumatology and Orthopedic Surgery, Faculty of Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Cardenal Herrera Oria, s/n 39011, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sánchez Crespo
authors.affiliation: Department of Traumatology and Orthopedic Surgery, Faculty of Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Cardenal Herrera Oria, s/n 39011, Spain.
authors.forename: M
authors.initials: M
authors.lastname: De la Red Gallego
authors.affiliation: Department of Traumatology and Orthopedic Surgery, Faculty of Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Cardenal Herrera Oria, s/n 39011, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pascual Carra
authors.affiliation: Department of Traumatology and Orthopedic Surgery, Faculty of Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Cardenal Herrera Oria, s/n 39011, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Rodriguez López
authors.affiliation: LADICIM-University of Cantabria, E.T.S. Ingenieros de Caminos, Canales y Puertos, Av/Los Castros, s/n 39005, Santander, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Diego Cavia
authors.affiliation: Department of Traumatology and Orthopedic Surgery, Faculty of Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Cardenal Herrera Oria, s/n 39011, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Garcés Zarzalejo
authors.affiliation: Department of Pathology, Marqués de Valdecilla University Hospital, University of Cantabria, Avda. Valdecilla, s/n 39008, Santander, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mayorga Fernández
authors.affiliation: LADICIM-University of Cantabria, E.T.S. Ingenieros de Caminos, Canales y Puertos, Av/Los Castros, s/n 39005, Santander, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ruiz Martínez
authors.affiliation: LADICIM-University of Cantabria, E.T.S. Ingenieros de Caminos, Canales y Puertos, Av/Los Castros, s/n 39005, Santander, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Carrascal Vaquero
authors.affiliation: Department of Medicine, Faculty of Medicine, Marqués de Valdecilla University Hospital, IDIVAL University of Cantabria, Avda. Valdecilla, s/n 39008, Santander, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Riancho Moral
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000473:pathology*; D017102:Fracture Healing; D017759:Fractures, Malunited / Q000473:pathology*; D010027:Osteotomy; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D010446:Peptide Fragments; D013876:Thiophenes; C081587:strontium ranelate; D019379:Teriparatide; C035748:parathyroid hormone (1-34)amide
keywords: Atrophic nonunion bone repair; Experimental pseudoartrosis; Fracture gap; Human PTH 1–84 (PTH 1–84); Strontium ranelate (SrR)