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Open AccessArticle

Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model

1
Faculty of Dentistry, McGill University, Montreal, QC H3A0C7, Canada
2
College of Dentistry, Imam Abdulrahman bin Faisal University, Dammam 34212, Saudi Arabia
3
Faculté de Pharmacie, Université de Montréal, Montréal, QC H3T 1J4, Canada
4
Research Center, Montreal Heart Institute, Montreal, QC H1T 1C8, Canada
5
Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt
6
Department of Periodontology (CHU/Rmes Inserm U1229/UIC11), Faculty of Dental Surgery, University of Nantes, 44042 Nantes, France
7
College of Dental Medicine, University of Sharjah, Sharjah, P.O. Box 27272, UAE
8
College of Dental Medicine, Qatar University, Doha P.O. 2713, Qatar
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(9), 1318; https://doi.org/10.3390/biom10091318
Received: 3 August 2020 / Revised: 9 September 2020 / Accepted: 10 September 2020 / Published: 14 September 2020
(This article belongs to the Special Issue Cholinesterase Research)
Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer’s disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing. View Full-Text
Keywords: acetylcholinesterase inhibitors; bone healing; osseointegration; donepezil; hemostasis acetylcholinesterase inhibitors; bone healing; osseointegration; donepezil; hemostasis
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MDPI and ACS Style

Al-Hamed, F.S.; Maria, O.M.; Phan, J.; Al Subaie, A.; Gao, Q.; Mansour, A.; Abu Nada, L.; Boukhatem, I.; Elkashty, O.A.; Tran, S.D.; Lordkipanidzé, M.; Badran, Z.; Tamimi, F. Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model. Biomolecules 2020, 10, 1318. https://doi.org/10.3390/biom10091318

AMA Style

Al-Hamed FS, Maria OM, Phan J, Al Subaie A, Gao Q, Mansour A, Abu Nada L, Boukhatem I, Elkashty OA, Tran SD, Lordkipanidzé M, Badran Z, Tamimi F. Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model. Biomolecules. 2020; 10(9):1318. https://doi.org/10.3390/biom10091318

Chicago/Turabian Style

Al-Hamed, Faez S.; Maria, Ola M.; Phan, Jeff; Al Subaie, Ahmed; Gao, Qiman; Mansour, Alaa; Abu Nada, Lina; Boukhatem, Imane; Elkashty, Osama A.; Tran, Simon D.; Lordkipanidzé, Marie; Badran, Zahi; Tamimi, Faleh. 2020. "Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model" Biomolecules 10, no. 9: 1318. https://doi.org/10.3390/biom10091318

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