title: The Impact of Strontium Ranelate on Metaphyseal Bone Healing in Ovariectomized Rats.
abstract: The following questions were addressed: whether therapy with strontium ranelate (SR) should be continued or interrupted if the fractures occur during SR treatment and whether SR could be applied directly after fracture to improve bone healing. Sprague-Dawley rats (3 month old) were ovariectomized (Ovx, n = 48) or left intact (n = 12). After 8 weeks, a bilateral transverse osteotomy of the tibia metaphysis was created in all rats. Ovx rats were divided into four groups: Ovx; SR applied directly after Ovx until osteotomy (prophylaxis, SR pr, 8 weeks); SR applied after osteotomy (therapy, SR th, 5 weeks); SR applied during the whole experiment (pr + th, 13 weeks). SR dosage was 625 mg/kg body weight/day, administered in the feed. Five weeks later, tibiae were analyzed by biomechanical, histological, micro-CT, and gene expression analyses. The SR pr + th treatment increased total bone mineral density (BMD), bone volume fraction, cortical BMD and volume, callus area and density, serum alkaline phosphatase, tartrate-resistant acid phosphatase mRNA, accelerated osteotomy bridging, and callus formation at weeks 2 and 3 of healing and decreased the osteoprotegerin/receptor activator of nuclear factor kB ligand mRNA ratio. SR th enlarged callus area and improved callus formation during the 5th week of healing. SR pr improved cortical BMD preserving bone after SR discontinuation (5-week rest); the bone healing was not affected. SR content in the tibia metaphysis was the highest in SR pr + th group and was not different between SR pr and SR th. SR has a positive effect on osteoporotic bone healing in rat and SR treatment can be continued after the fracture occurs or applied directly after the fracture.
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Robert-Koch St. 40, 37075, Göttingen, Germany. komrakova@yahoo.com.
authors.forename: Marina
authors.initials: M
authors.lastname: Komrakova
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Robert-Koch St. 40, 37075, Göttingen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Weidemann
authors.affiliation: Department of Radiology, University of Göttingen, Robert-Koch 40, 37075, Göttingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.affiliation: Department of Medical Microbiology, Subdivision of General Hygiene and Environmental Health, University of Göttingen, Humboldallee 34a, 37073, Göttingen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Ebert
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Robert-Koch St. 40, 37075, Göttingen, Germany.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tezval
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Robert-Koch St. 40, 37075, Göttingen, Germany.
authors.forename: Klaus Michael
authors.initials: KM
authors.lastname: Stuermer
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Robert-Koch St. 40, 37075, Göttingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Sehmisch
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000150:complications; D058866:Osteoporotic Fractures / Q000188:drug therapy; D010027:Osteotomy; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D013876:Thiophenes; C081587:strontium ranelate
keywords: Bone healing; Osteoporosis; Rat model; Strontium ranelate