On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model

Abstract Bone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of dis...

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Autores principales:	Mehran Ashrafi, Farzan Ghalichi, Behnam Mirzakouchaki, Manuel Doblare
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/474ece590eb74e48aebaa34540f9c87b
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spelling	oai:doaj.org-article:474ece590eb74e48aebaa34540f9c87b2021-12-02T14:06:49ZOn the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model10.1038/s41598-021-82502-y2045-2322https://doaj.org/article/474ece590eb74e48aebaa34540f9c87b2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82502-yhttps://doaj.org/toc/2045-2322Abstract Bone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of disuse, or assessing the long-term evolution of the bone surrounding prostheses after implantation. A particular case of study is the bone remodeling process after dental implantation. Despite the overall success of this type of implants, the increasing life expectancy in developed countries has boosted the demand for dental implants in patients with osteoporosis. Although several studies demonstrate a high success rate of dental implants in osteoporotic patients, it is also known that the healing time and the failure rate increase, necessitating the adoption of pharmacological measures to improve bone quality in those patients. However, the general efficacy of these antiresorptive drugs for osteoporotic patients is still controversial, requiring more experimental and clinical studies. In this work, we investigate the effect of different doses of several drugs, used nowadays in osteoporotic patients, on the evolution of bone density after dental implantation. With this aim, we use a pharmacokinetic–pharmacodynamic (PK/PD) mathematical model that includes the effect of antiresorptive drugs on the RANK/RANK-L/OPG pathway, as well as the mechano-chemical coupling with external mechanical loads. This mechano-PK/PD model is then used to analyze the evolution of bone in normal and osteoporotic mandibles after dental implantation with different drug dosages. We show that using antiresorptive agents such as bisphosphonates or denosumab increases bone density and the associated mechanical properties, but at the same time, it also increases bone brittleness. We conclude that, despite the many limitations of these very complex models, the one presented here is capable of predicting qualitatively the evolution of some of the main biological and chemical variables associated with the process of bone remodeling in patients receiving drugs for osteoporosis, so it could be used to optimize dental implant design and coating for osteoporotic patients, as well as the drug dosage protocol for patient-specific treatments.Mehran AshrafiFarzan GhalichiBehnam MirzakouchakiManuel DoblareNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mehran Ashrafi Farzan Ghalichi Behnam Mirzakouchaki Manuel Doblare On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model
description	Abstract Bone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of disuse, or assessing the long-term evolution of the bone surrounding prostheses after implantation. A particular case of study is the bone remodeling process after dental implantation. Despite the overall success of this type of implants, the increasing life expectancy in developed countries has boosted the demand for dental implants in patients with osteoporosis. Although several studies demonstrate a high success rate of dental implants in osteoporotic patients, it is also known that the healing time and the failure rate increase, necessitating the adoption of pharmacological measures to improve bone quality in those patients. However, the general efficacy of these antiresorptive drugs for osteoporotic patients is still controversial, requiring more experimental and clinical studies. In this work, we investigate the effect of different doses of several drugs, used nowadays in osteoporotic patients, on the evolution of bone density after dental implantation. With this aim, we use a pharmacokinetic–pharmacodynamic (PK/PD) mathematical model that includes the effect of antiresorptive drugs on the RANK/RANK-L/OPG pathway, as well as the mechano-chemical coupling with external mechanical loads. This mechano-PK/PD model is then used to analyze the evolution of bone in normal and osteoporotic mandibles after dental implantation with different drug dosages. We show that using antiresorptive agents such as bisphosphonates or denosumab increases bone density and the associated mechanical properties, but at the same time, it also increases bone brittleness. We conclude that, despite the many limitations of these very complex models, the one presented here is capable of predicting qualitatively the evolution of some of the main biological and chemical variables associated with the process of bone remodeling in patients receiving drugs for osteoporosis, so it could be used to optimize dental implant design and coating for osteoporotic patients, as well as the drug dosage protocol for patient-specific treatments.
format	article
author	Mehran Ashrafi Farzan Ghalichi Behnam Mirzakouchaki Manuel Doblare
author_facet	Mehran Ashrafi Farzan Ghalichi Behnam Mirzakouchaki Manuel Doblare
author_sort	Mehran Ashrafi
title	On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model
title_short	On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model
title_full	On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model
title_fullStr	On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model
title_full_unstemmed	On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model
title_sort	on the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/474ece590eb74e48aebaa34540f9c87b
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On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model

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