title: Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta.
abstract: Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research.
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Changgui
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Huiqiao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Lianfu
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000000981:diagnostic imaging* / Q000235:genetics / Q000517:prevention & control*; D015994:Incidence; D051379:Mice; D008817:Mice, Mutant Strains; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics; D013876:Thiophenes / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D013876:Thiophenes; C081587:strontium ranelate
keywords: BONE HISTOMORPHOMETRY; FRACTURE PREVENTION; OIM; OSTEOGENESIS IMPERFECTA; STRONTIUM RANELATE