Simvastatin application to augment facial jaw bone in a dog model: pilot study.
BACKGROUND
Locally injected simvastatin (SIM) has been shown to induce bone growth in rat models. The purpose of this study is to evaluate the effects of locally injected simvastatin in several human-like clinical situations in a beagle dog model.


METHODS
Four beagle dogs completed the study and were used in a split-mouth design. Dehiscence defects of 5 × 3 mm were created bilaterally on the lateral aspect of the mandibular second premolar (PM2) mesial roots including removal of root cementum. At the same surgery, porous hydroxyapatite-collagen grafts with resorbable membranes with or without 10-mg SIM were placed buccal to the mandibular first molars (M1). One week later, three weekly local injections of 10-mg SIM in ethanol and contralateral ethanol alone were initiated at three sites through the buccal mucosa: 1) 6 mm apical to the cemento-enamel junction (CEJ) of the maxillary fourth premolar (PM4; thin bone over root); 2) 6 mm apical to the CEJ of PM2 (dehiscence defect); and 3) 10 mm distoapical to the CEJ of the maxillary canine (edentulous ridge). Dogs were euthanized 2 months after the final injections. Block sections were harvested and specimens were decalcified and stained with hematoxylin and eosin. Histomorphometry was performed using digitized photographs and analyzed with distribution-free rank tests.


RESULTS
Regarding M1, the distance between CEJ and the alveolar crest was significantly more coronal in the SIM group (P = 0.038). Regarding the edentulous ridge, the width of new bone was significantly greater in SIM injection specimens (P = 0.0164). Regarding PM2, buccal bone in the dehiscence defects lacking periosteum was not augmented in the SIM group. Regarding PM4, the total width of bone 5 mm apical to the coronal height of contour (thin buccal bone covering the root) was significantly wider on the SIM side (SIM, 0.63 ± 0.53 mm; contralateral ethanol alone, 0.25 ± 0.19 mm; P = 0.0098).


CONCLUSIONS
Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.
Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583–0740, USA.
John
J
Rutledge
Matthew D
MD
Schieber
Judd M
JM
Chamberlain
Matthew
M
Byarlay
Amy C
AC
Killeen
Peter J
PJ
Giannini
David B
DB
Marx
Richard A
RA
Reinhardt
D000539:Alveolar Process / Q000187:drug effects*; D000540:Alveolar Ridge Augmentation / Q000379:methods; D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D004285:Dogs; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008334:Mandible; D016348:Osseointegration / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D011897:Random Allocation; D019821:Simvastatin / Q000494:pharmacology*
D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin