A mechano-chemo-biological model for bone remodeling with a new mechano-chemo-transduction approach

Ashrafi, Mehran; Gubaua, José Eduardo; Pereira, Jucélio Tomás; Gahlichi, Farzan; Doblaré, M.

doi:10.1007/s10237-020-01353-0

Cited by 19 publications

(17 citation statements)

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“…www.nature.com/scientificreports/ of denosumab and Ibandronate. As shown in 34 and in Fig. 3, the ash fraction decreases during the first stage of remodeling, because of the activity of osteoclasts tends to increase.…”

Section: Figurementioning

confidence: 80%

“…1. As mentioned in our previous study 34 , simplifications such as considering only the RANK/RANK-L/OPG biochemical pathway, or in the reaction rate assumed for the receptor-ligand reactions, or discarding the effect of osteocytes in the mechanosensing process, should be progressively overcome. 2.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the bone remodeling model, only a brief review is done here. For additional details, the reader may consult 34 . That mechano-chemo-biological model is based on the previous work of Lemaire et al 27 .…”

Section: Bone Remodeling Modelmentioning

confidence: 99%

“…In particular, mechanical forces change the energy barrier of the molecules and disrupt the binding/unbinding of receptors and ligands in chemical reactions, while damage interrupts the communication channels between cells, thus reducing the level of the mechanical signal. Therefore, we hypothesized in a previous paper 34 that the reaction rates of the receptor and ligand change as follows:…”

Section: Chemical Reactions Involved In Bone Remodeling the Receptor Activator For Nuclear Kappa-b Rankmentioning

confidence: 99%

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

Ashrafi

Ghalichi

Mirzakouchaki

et al. 2021

Sci Rep

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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.

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Section: Figurementioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Bone Remodeling Modelmentioning

confidence: 99%

Section: Chemical Reactions Involved In Bone Remodeling the Receptor Activator For Nuclear Kappa-b Rankmentioning

confidence: 99%

See 2 more Smart Citations

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

Ashrafi

Ghalichi

Mirzakouchaki

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, mechano-chemo-biological models, which derive from the ODE models previously mentioned, have appeared. Very few articles have considered this type of models in their investigations (Klika et al, 2013;Avval et al, 2014;Lerebours et al, 2016;Pastrama et al, 2018;Martin et al, 2019;Ashrafi et al, 2020). Nevertheless, we think that they are very promising as they englobe each of mechanical, biological, and biochemical features of bone.…”

Section: Mathematical Models Of Bone Remodelingmentioning

confidence: 99%

Toward a Mathematical Modeling of Diseases’ Impact on Bone Remodeling: Technical Review

Oumghar

Barkaoui

Chabrand

2020

Front. Bioeng. Biotechnol.

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A wide variety of bone diseases have hitherto been discovered, such as osteoporosis, Paget's disease, osteopetrosis, and metastatic bone disease, which are not well defined in terms of changes in biochemical and mechanobiological regulatory factors. Some of these diseases are secondary to other pathologies, including cancer, or to some clinical treatments. To better understand bone behavior and prevent its deterioration, bone biomechanics have been the subject of mathematical modeling that exponentially increased over the last years. These models are becoming increasingly complex. The current paper provides a timely and critical analysis of previously developed bone remodeling mathematical models, particularly those addressing bone diseases. Besides, mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, which englobe bone disease and its treatment's effect on bone health. Therefore, the review starts by presenting bone remodeling cycle and mathematical models describing this process, followed by introducing some bone diseases and discussing models of pathological mechanisms affecting bone, and concludes with exhibiting the available bone treatment procedures considered in the PK/PD models.

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Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients

Ait Oumghar,

Barkaoui,

Merzouki

et al. 2023

Numer Methods Biomed Eng

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Breast cancer is a significant public health issue affecting women worldwide. While advancements in treatment options have led to improved survival rates, the impact of breast cancer and its treatments on bone health cannot be overlooked. Bone remodeling is a complex process regulated by the delicate balance between bone formation and resorption. Any disruption to this balance can lead to decreased bone density, increased fracture risk, and compromised physical function. To investigate the effects of breast cancer and its treatments on bone remodeling, a finite element model was developed in this study. This model incorporated bone remodeling equations to simulate the mechanical behavior of bone under different conditions. The ABAQUS/UMAT software was used to simulate the behavior of bone tissue under the influence of breast cancer and treatments. Our findings suggest that bone loss is more pronounced after secondary breast cancer and treatment, leading to bone loss (6%–19% decrease in BV/TV), reduced bone stimulation, and decreased effectiveness of physical activity on recovery. These results highlight the importance of early intervention and management of bone health in breast cancer patients to mitigate the negative impact of cancer and treatment on bone remodeling.

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A mechano-chemo-biological model for bone remodeling with a new mechano-chemo-transduction approach

Cited by 19 publications

References 100 publications

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

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

Toward a Mathematical Modeling of Diseases’ Impact on Bone Remodeling: Technical Review

Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients

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