title: Can low doses of simvastatin enhance fracture healing? An experimental study in rabbits.
abstract: Several observational and experimental studies have investigated the potential anabolic effects of statins on undisturbed bone but only a few recent studies have examined the effect of statins on skeletal repair. The goal of the study is to investigate any potential early anabolic effect of the systemic administration of simvastatin in low doses (based on earlier safety and efficacy studies on undisturbed bone) on fracture healing. Fifty-four skeletally mature male New Zealand White rabbits were used for the study. The rabbits were assigned to one of three experimental groups: a control group, and two groups that were orally administrated a diet with 10 and 30 mg/kg/day of simvastatin, respectively. A complete biochemical blood count was performed to exclude drug-induced complications. Half of the animals of each group were sacrificed at 15 days and the other half at 30 days after surgery at which time intervals healing quality was assessed. The bones were subjected to biomechanical testing, histomorphometric analysis and peripheral quantitative computed tomography. In animals received simvastatin of 30 mg/kg/day a significant reduction of BMD, stiffness, and energy absorbed to failure were observed. At 15 days, the amount of cartilaginous callus formation was reduced, and the void space was significantly increased, in the animals of both groups that received simvastatin when compared to the control group (p<.05). Our results suggest that simvastatin doses of 30 mg/kg/day may have a negative anabolic effect on callus formation in rabbits, whereas doses of 10 mg/kg/day seem not to produce a significant positive or a negative effect, especially at the early stages of fracture remodeling.
authors.affiliation: 2nd Department of Orthopaedic and Trauma Surgery, G. Genimmatas General Hospital of Athens, 154 Mesogeion Ave, 115 24 Athens, Greece. chissas@yahoo.gr
authors.forename: Dionysios
authors.initials: D
authors.lastname: Chissas
authors.forename: George
authors.initials: G
authors.lastname: Stamatopoulos
authors.forename: Dionysios
authors.initials: D
authors.lastname: Verettas
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kazakos
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.forename: George
authors.initials: G
authors.lastname: Agrogiannis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papaeliou
authors.forename: Emmanouel
authors.initials: E
authors.lastname: Agapitos
authors.forename: Alexia
authors.initials: A
authors.lastname: Balanika
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Papadopoulou
authors.forename: George
authors.initials: G
authors.lastname: Anastopoulos
authors.forename: Panagiotis G
authors.initials: PG
authors.lastname: Ntagiopoulos
authors.forename: Antonios
authors.initials: A
authors.lastname: Asimakopoulos
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011817:Rabbits; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D014458:Ulna Fractures / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D019821:Simvastatin