title: Systemic treatment with strontium ranelate accelerates the filling of a bone defect and improves the material level properties of the healing bone.
abstract: Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.5 mm in diameter were created in 6-month-old female rats orally fed SrRan (625 mg/kg/d; 5/7 days) or vehicle for 4, 8, or 12 weeks (10 rats per group per time point) from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (µCT) and material level properties by nanoindentation analysis. µCT analysis showed that SrRan administration significantly improved microarchitecture of trabecular bone growing into the defect after 8 and 12 weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with different kinetics compared to trabecular bone, as the effects were already significant after 4 weeks. Nanoindentation analysis demonstrated that SrRan treatment significantly increased material level properties of both trabecular bone and cortical bone filling the defect compared to vehicle. SrRan accelerates the filling of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively.
authors.affiliation: Division of Bone Disease, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, 1211 Geneva, Switzerland.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zacchetti
authors.affiliation: Division of Bone Disease, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, 1211 Geneva, Switzerland.
authors.forename: Romain
authors.identifier: 0000-0001-5439-4226
authors.initials: R
authors.lastname: Dayer
authors.affiliation: Division of Bone Disease, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, 1211 Geneva, Switzerland.
authors.forename: René
authors.initials: R
authors.lastname: Rizzoli
authors.affiliation: Division of Bone Disease, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, 1211 Geneva, Switzerland.
authors.forename: Patrick
authors.identifier: 0000-0002-7150-2433
authors.initials: P
authors.lastname: Ammann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000293:injuries* / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D013876:Thiophenes; C081587:strontium ranelate; D007334:Insulin-Like Growth Factor I