title: Impact of local and systemic alendronate on simvastatin-induced new bone around periodontal defects.
abstract: BACKGROUND
  Simvastatin has been shown to stimulate new bone growth on rat mandibles, but much of the bone is lost over time. The purpose of this study is to evaluate the impact of a locally or systemically applied antiresorptive agent (alendronate) on simvastatin-induced bone formation in and adjacent to a rat periodontal defect.
  
  
  METHODS
  Fenestration defects were created over mandibular molar roots in 65 mature female Sprague-Dawley rats. Two weeks later, animals were divided into eight groups of eight to nine rats, and three weekly injections around the defect were applied: 1) 0.5 mg simvastatin in ethanol (SIM-EtOH); 2) 0.5 mg simvastatin in alendronate-cyclodextrin conjugate (SIM-ALN-CD); 3) EtOH alone; 4) ALN-CD alone; or 5) no injections. Twenty-four animals were evaluated for new bone width around the defect 21 days after the last injections (short-term) and 41 rats were followed for 48 days (long-term). Three SIM-EtOH groups of long-term rats also were subjected to 2 weeks of daily systemic ALN or saline either during or 3 to 4 weeks after SIM-EtOH injections. Decalcified, hematoxylin-and-eosin-stained cross-sections of the defect area were analyzed for new bone width and groups were compared using mixed-model analyses of variance.
  
  
  RESULTS
  All groups showed nearly 100% bone fill, with no differences among the short-term groups. However, in the long-term animals, two-fold to three-fold more new bone width (≤ 0.004) was seen around the periphery of the defect with the use of systemic ALN after SIM-EtOH injections (0.93 ± 0.12 and 0.78 ± 0.11 mm with early and late systemic ALN, respectively) compared to local SIM/ALN-CD preparations (0.32 ± 0.10 mm) or short-term SIM-EtOH injections (0.35 ± 0.10 mm). No significant new cementum formation or ankylosis was noted.
  
  
  CONCLUSIONS
  The use of a short course of systemic ALN during the healing period after bone anabolic SIM injections has the potential to enhance local bone augmentation.
authors.affiliation: Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583-0740, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Killeen
authors.forename: Pota A
authors.initials: PA
authors.lastname: Rakes
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Schmid
authors.forename: Yijia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nagamani
authors.initials: N
authors.lastname: Narayana
authors.forename: David B
authors.initials: DB
authors.lastname: Marx
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Payne
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Reinhardt
mesh_terms: D000287:Administration, Topical; D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D016301:Alveolar Bone Loss / Q000188:drug therapy*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008334:Mandible / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D019386:Alendronate