Impact of local and systemic alendronate on simvastatin-induced new bone around periodontal defects

Amy C Killeen, Pota A. Rakes, Marian J. Schmid, Yijia Zhang, Nagamani Narayana, David B. Marx, Jeffrey B Payne, Dong Wang, Richard A Reinhardt

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 (longterm). 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 ALNafter SIM-EtOH injections (0.93 ± 0.12 and 0.78 ± 0.11mmwith 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1463-1471
Number of pages9
JournalJournal of periodontology
Volume83
Issue number12
DOIs
StatePublished - Dec 1 2012

Fingerprint

Alendronate
Simvastatin
Bone and Bones
Injections
Bone Density Conservation Agents
Dental Cementum
Ankylosis
Bone Development
Cyclodextrins
Hematoxylin
Eosine Yellowish-(YS)
Mandible
Osteogenesis
Sprague Dawley Rats
Analysis of Variance
Ethanol

Keywords

  • Alendronate
  • Bone regeneration
  • Drug delivery systems
  • Histology
  • Simvastatin
  • Wound healing

ASJC Scopus subject areas

  • Periodontics

Cite this

Impact of local and systemic alendronate on simvastatin-induced new bone around periodontal defects. / Killeen, Amy C; Rakes, Pota A.; Schmid, Marian J.; Zhang, Yijia; Narayana, Nagamani; Marx, David B.; Payne, Jeffrey B; Wang, Dong; Reinhardt, Richard A.

In: Journal of periodontology, Vol. 83, No. 12, 01.12.2012, p. 1463-1471.

Research output: Contribution to journalArticle

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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 (longterm). 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 ALNafter SIM-EtOH injections (0.93 ± 0.12 and 0.78 ± 0.11mmwith 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. Conclusion: 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.",
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AU - Killeen, Amy C

AU - Rakes, Pota A.

AU - Schmid, Marian J.

AU - Zhang, Yijia

AU - Narayana, Nagamani

AU - Marx, David B.

AU - Payne, Jeffrey B

AU - Wang, Dong

AU - Reinhardt, Richard A

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N2 - 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 (longterm). 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 ALNafter SIM-EtOH injections (0.93 ± 0.12 and 0.78 ± 0.11mmwith 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. Conclusion: 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.

AB - 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 (longterm). 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 ALNafter SIM-EtOH injections (0.93 ± 0.12 and 0.78 ± 0.11mmwith 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. Conclusion: 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.

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KW - Drug delivery systems

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KW - Wound healing

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