Simvastatin application to augment facial jaw bone in a dog model: Pilot study

John Rutledge, Matthew D. Schieber, Judd M. Chamberlain, Matthew R Byarlay, Amy C Killeen, Peter J Giannini, David B. Marx, Richard A Reinhardt

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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). Conclusion: Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.

Original languageEnglish (US)
Pages (from-to)597-605
Number of pages9
JournalJournal of periodontology
Volume82
Issue number4
DOIs
StatePublished - Apr 1 2011

Fingerprint

Facial Bones
Simvastatin
Jaw
Dogs
Dental Enamel
Zygoma
Injections
Ethanol
Bicuspid
Bone and Bones
Dental Cementum
Periosteum
Cheek
Bone Development
Mouth Mucosa
Durapatite
Hematoxylin
Eosine Yellowish-(YS)
Osteogenesis
Mouth

Keywords

  • Bone regeneration
  • Drug targeting
  • Histology
  • Simvastatin
  • Wound healing

ASJC Scopus subject areas

  • Periodontics

Cite this

Simvastatin application to augment facial jaw bone in a dog model : Pilot study. / Rutledge, John; Schieber, Matthew D.; Chamberlain, Judd M.; Byarlay, Matthew R; Killeen, Amy C; Giannini, Peter J; Marx, David B.; Reinhardt, Richard A.

In: Journal of periodontology, Vol. 82, No. 4, 01.04.2011, p. 597-605.

Research output: Contribution to journalArticle

Rutledge, John ; Schieber, Matthew D. ; Chamberlain, Judd M. ; Byarlay, Matthew R ; Killeen, Amy C ; Giannini, Peter J ; Marx, David B. ; Reinhardt, Richard A. / Simvastatin application to augment facial jaw bone in a dog model : Pilot study. In: Journal of periodontology. 2011 ; Vol. 82, No. 4. pp. 597-605.
@article{7172f36335da419ba7186369933702a7,
title = "Simvastatin application to augment facial jaw bone in a dog model: Pilot study",
abstract = "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). Conclusion: Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.",
keywords = "Bone regeneration, Drug targeting, Histology, Simvastatin, Wound healing",
author = "John Rutledge and Schieber, {Matthew D.} and Chamberlain, {Judd M.} and Byarlay, {Matthew R} and Killeen, {Amy C} and Giannini, {Peter J} and Marx, {David B.} and Reinhardt, {Richard A}",
year = "2011",
month = "4",
day = "1",
doi = "10.1902/jop.2010.100214",
language = "English (US)",
volume = "82",
pages = "597--605",
journal = "Journal of Periodontology",
issn = "0022-3492",
publisher = "American Academy of Periodontology",
number = "4",

}

TY - JOUR

T1 - Simvastatin application to augment facial jaw bone in a dog model

T2 - Pilot study

AU - Rutledge, John

AU - Schieber, Matthew D.

AU - Chamberlain, Judd M.

AU - Byarlay, Matthew R

AU - Killeen, Amy C

AU - Giannini, Peter J

AU - Marx, David B.

AU - Reinhardt, Richard A

PY - 2011/4/1

Y1 - 2011/4/1

N2 - 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). Conclusion: Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.

AB - 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). Conclusion: Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.

KW - Bone regeneration

KW - Drug targeting

KW - Histology

KW - Simvastatin

KW - Wound healing

UR - http://www.scopus.com/inward/record.url?scp=79955002693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955002693&partnerID=8YFLogxK

U2 - 10.1902/jop.2010.100214

DO - 10.1902/jop.2010.100214

M3 - Article

C2 - 21043796

AN - SCOPUS:79955002693

VL - 82

SP - 597

EP - 605

JO - Journal of Periodontology

JF - Journal of Periodontology

SN - 0022-3492

IS - 4

ER -