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

Al-Hamed, Faez Saleh; Maria, Ola M.; Phan, Jeff; Subaie, Ahmed Al; Gao, Qiman; Mansour, Alaa; Nada, Lina Abu; Boukhatem, Imane; Elkashty, Osama A.; Lordkipanidzé, Marie; Badran, Zahi; Tamimi, Faleh

doi:10.3390/biom10091318

Cited by 9 publications

(17 citation statements)

References 51 publications

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“…Furthermore, the comparable healing observed in empty defects raises a concern regarding the suitability of this bone defect model. However, this model was found to be reliable to study the effect of medications on bone healing based on previous studies Al-Hamed et al, 2020). Therefore, to assess the regenerative potential of L-PRP, it is advised to use a larger bone defect instead of the one used in this study.…”

Section: Discussionmentioning

confidence: 96%

“…This model involves minimally invasive surgery and reduces animal suffering. We have already used it in our previous studies with minimal complications (Al‐Hamed et al, 2020; Al‐Hamed et al, 2021). However, in the current study, our rats were euthanized because of bone fractures.…”

Section: Discussionmentioning

confidence: 99%

“…The main limitation of this study was that the effects of L‐PRPs on bone healing were assessed only at one time point, namely 2 weeks after surgery. This time point was selected because it allows accurate assessment of the early stages of bone healing in terms of osteoblastic activity induced by medications or biological materials as reported in our previous studies (Al Subaie, Laurenti et al 2016; Al‐Hamed et al, 2020, 2021). Furthermore, assessing bone healing at shorter time points (<1 week) does not show anything on μ‐CT because there is no mineralization yet, and longer time points do not show differences because the defect is completely healed, as we performed the experiment in a group of young rats which have rapid healing ability.…”

Section: Discussionmentioning

confidence: 99%

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Differences in platelet‐rich plasma composition influence bone healing

Al-Hamed

Abu-Nada

Rodan

et al. 2021

J Clinic Periodontology

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Aim: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing.Materials and Methods: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology.Results: Double-spin L-PRP contained higher concentrations of platelets than singlespin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differences in platelet‐rich plasma composition influence bone healing

Al-Hamed

Abu-Nada

Rodan

et al. 2021

J Clinic Periodontology

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“…15 In addition, this was in agreement with our in vivo study, in which we showed that the AChEI, donepezil, did not affect hemostasis and platelet function. 32 Thus AChEI use does not appear to be associated with increased bleeding risk.…”

Section: Discussionmentioning

confidence: 97%

Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non‐hypertensive Alzheimer's patients

Al-Hamed

Kouniaris

Tamimi

et al. 2021

A&D Transl Res & Clin Interv

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Introduction: Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non-hypertensive AD.Methods: A nested case-control study was conducted to estimate the risk of bleeding and ischemic events (angina, myocardial infarction [MI], and stroke) in patients with AD. This study was conducted using the UK Clinical Practice Research Datalink and Hospital Episode Statistics (HES) databases. The study cohort consisted of AD patients ≥65 years of age. The case groups included all AD subjects in the database who had a bleeding or ischemic event during the cohort follow-up. Four controls were selected for each case. Patients were classified as current users or past users based on a 60-day threshold of consuming the drug. Simple and multivariable conditional logistic regression analyses were used to calculate the adjusted odds ratio for bleeding events and cardiovascular events. Results:We identified 507 cases and selected 2028 controls for the bleeding event cohort and 555 cases and 2220 controls for the ischemic event cohort. The adjusted odds ratio (OR) (95% confidence interval [CI]) for the association of AChEI use was 0.93 (0.75 to 1.16) for bleeding events, 2.58 (1.01 to 6.59) for angina, and 1.89 (1.07 to 3.33) for MI. Past users of AChEIs were also at increased risk of stroke (1.51 [1.00 to 2.27]).Discussion: This is the first study assessing the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Our findings could be of great interest for clinicians and researchers working on AD.

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“…In another article by Al-Hamed et al [10], postoperative administration of donepezil on bone healing was studied in the group of Sprague-Dawley rats. After two weeks of donepezil administration, rats were euthanized, and their bones were analyzed by Micro-CT and histology, with the authors concluding that bone defects and implant osseointegration were significantly reduced compared to the saline-treated rats.…”

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confidence: 99%