Study of the combined effects of PTH treatment and mechanical loading in postmenopausal osteoporosis using a new mechanistic PK-PD model

Lavaill, Maxence; Trichilo, Silvia; Scheiner, Stefan; Forwood, Mark R.; Cooper, David M.L.; Pivonka, Peter

doi:10.1007/s10237-020-01307-6

Cited by 16 publications

(11 citation statements)

References 35 publications

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“…Furthermore, such studies should explore the influence of the body on mechanical stimulation. It is gratifying that mechanism-driven biology and biochemistry have been put into mathematical systems biology formats, this will certainly lead the research field to a more precise direction ( Pastrama et al, 2018 ; Lavaill et al, 2020 ; Larcher and Scheiner, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts

Liu

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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Osteoclasts and osteoblasts play a major role in bone tissue homeostasis. The homeostasis and integrity of bone tissue are maintained by ensuring a balance between osteoclastic and osteogenic activities. The remodeling of bone tissue is a continuous ongoing process. Osteoclasts mainly play a role in bone resorption, whereas osteoblasts are mainly involved in bone remodeling processes, such as bone cell formation, mineralization, and secretion. These cell types balance and restrict each other to maintain bone tissue metabolism. Bone tissue is very sensitive to mechanical stress stimulation. Unloading and loading of mechanical stress are closely related to the differentiation and formation of osteoclasts and bone resorption function as well as the differentiation and formation of osteoblasts and bone formation function. Consequently, mechanical stress exerts an important influence on the bone microenvironment and bone metabolism. This review focuses on the effects of different forms of mechanical stress stimulation (including gravity, continuously compressive pressure, tensile strain, and fluid shear stress) on osteoclast and osteoblast function and expression mechanism. This article highlights the involvement of osteoclasts and osteoblasts in activating different mechanical transduction pathways and reports changings in their differentiation, formation, and functional mechanism induced by the application of different types of mechanical stress to bone tissue. This review could provide new ideas for further microscopic studies of bone health, disease, and tissue damage reconstruction.

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Section: Discussionmentioning

confidence: 99%

Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts

Liu

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Recently, PMO problem has been further investigated in the mechanobiological model described in [85]. PMO effect has been incorporated while taking into consideration the mechanical loading applied on the bone.…”

Section: Mechanobiological Mathematical Models Of a Pathological Bonementioning

confidence: 99%

“…Based on the outcomes, they formulated another function that will control preosteoblast proliferation, lining cells differentiation, and active osteoclast apoptosis. Another recent study [85] has been based on [86], have investigated the same thing, which is PTH effect on bone density. This time, authors have included PTH into their bone remodeling mathematical model by modifying active osteoblasts apoptosis rate multiplying the normal parameter value by the function representing PTH drug concentration.…”

Section: Mechanobiological Models Treating Bone Healing and Drugs Effectmentioning

confidence: 99%

Mechanobiological Behavior of a Pathological Bone

Oumghar¹,

Barkaoui²,

Chabrand³

2021

Biomechanics and Functional Tissue Engineering

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Bone density and bone microarchitecture are two principle parameters needed for the evaluation of mechanical bone performance and consequently the detection of bone diseases. The mechanobiological behavior of the skeletal tissue has been described through several mathematical models. Generally, these models fingerboard different length scale processes, such as the mechanical, the biological, and the chemical ones. By means of the mechanical stimulus and the biological factors involved in tissue regeneration, bone cells’ behavior and bone volume changes are determined. The emergence of bone diseases leads to disrupt the bone remodeling process and thus, induces bone mechanical properties’ alteration. In the present chapter, an overview of bone diseases and their relationship with bone density alteration will be presented. Besides, several studies treating bone diseases’ effect on bone remodeling will be discussed. Finally, the mechanobiological models proposed to treat bone healing and drugs’ effect on bone, are going to be reviewed. For this sake, the chapter is subdivided into three main sequences: (i) Bone remodeling, (ii) Bone deterioration causes, (iii) Mathematical models of a pathological bone, and (iv) Mechanobiological models treating bone healing and drugs effect.

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“…However, computational modifications should be elaborated to translate the model to humans. In the same spirit, Lavaill et al (2020) have addressed PTH treatment's effect on PMO healing. However, this time, the authors have considered both anabolic and catabolic PTH actions according to the administration type.…”

Section: Lavaill Et Al 2020mentioning

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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Study of the combined effects of PTH treatment and mechanical loading in postmenopausal osteoporosis using a new mechanistic PK-PD model

Cited by 16 publications

References 35 publications

Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts

Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts

Mechanobiological Behavior of a Pathological Bone

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

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