title: Systemic Treatment with Strontium Ranelate Does Not Influence the Healing of Femoral Mid-shaft Defects in Rats.
abstract: Strontium ranelate (SrR) has both bone anabolic and anti-resorption properties and has therefore the potential to increase the healing of bone defects. The aim of the present study was to investigate the effect of systemic treatment with SrR during the healing of cortical bone defects in rats. In addition, the vertebral bodies were examined in order to elucidate the effect of short-term treatment with SrR on intact trabecular bone. Sixty 16-week-old female Wistar rats were randomized into four groups. A cylindrical defect was drilled through the anterior cortex of the mid-femoral diaphysis in both hind limbs. Two of the groups were treated with SrR (900 mg/kg b.w.) mixed into the food and two groups served as controls. The animals were euthanized after either 3 or 8 weeks of treatment. Healing of the defects was analyzed with µCT, mechanical testing, and stereology. Treatment with SrR resulted in increased thickness of the defects after 3 weeks of treatment, whereas no effect on bone volume fraction (BV/TV), mechanical properties (maximum strength and maximum stiffness), periosteal callus volume, or osteoclast-covered bone surfaces (Oc.S/BS) after either 3 or 8 weeks of treatment was found. Furthermore, SrR increased the bone material density (ρ) of the vertebral bodies, and tended to increase BV/TV after 8 weeks of treatment (p = 0.087). The mechanical properties of the vertebral bodies were not influenced by SrR treatment. In conclusion, 3 weeks of treatment with SrR increased the thickness of the healing mid-femoral cortical bone defects in rats, but did not influence BV/TV, mechanical properties, periosteal callus volume, or Oc.S/BS after either 3 or 8 weeks. Furthermore, SrR had no effect on the microstructure and mechanical properties of the vertebral bodies.
authors.affiliation: Department of Biomedicine, Health, Aarhus University, Wilhelm Meyers Allé 3, 8000, Aarhus C, Denmark. jbve@biomed.au.dk.
authors.forename: Jens Bay
authors.identifier: http://orcid.org/0000-0003-1973-3127
authors.initials: JB
authors.lastname: Vegger
authors.affiliation: Department of Biomedicine, Health, Aarhus University, Wilhelm Meyers Allé 3, 8000, Aarhus C, Denmark. mb@biomed.au.dk.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Brüel
authors.affiliation: Department of Biomedicine, Health, Aarhus University, Wilhelm Meyers Allé 3, 8000, Aarhus C, Denmark. tgs@biomed.au.dk.
authors.forename: Thomas Givskov
authors.initials: TG
authors.lastname: Sørensen
authors.affiliation: Department of Biomedicine, Health, Aarhus University, Wilhelm Meyers Allé 3, 8000, Aarhus C, Denmark. jst@ana.au.dk.
authors.forename: Jesper Skovhus
authors.initials: JS
authors.lastname: Thomsen
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000293:injuries; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D013876:Thiophenes; C081587:strontium ranelate
keywords: Biomechanics; Bone defects; Bone healing; MicroCT; Rats; Strontium ranelate