Prediction of denosumab effects on bone remodeling: A combined pharmacokinetics and finite element modeling

Hambli, Ridha; Boughattas, Mohamed Hafedh; Daniel, Jean-Luc; Kourta, Azeddine

doi:10.1016/j.jmbbm.2016.03.010

Cited by 25 publications

(9 citation statements)

References 42 publications

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“…In the work of Hambli et al (2016), denosumab's effect on the bone-specific region, which is the proximal femur of…”

Section: Mathematical Models: Mechanistic Pharmacokinetic/pharmacodynmentioning

confidence: 99%

“…Adding a term reflecting denosumab-RANKL binding in the calculation of RANKL concentration. Scheiner et al, 2014;Martínez-Reina and Pivonka, 2019 Paracrine parameter of osteoblasts The paracrine parameter depends on a function of denosumab concentration, this latter induce low RANKL effect on osteoclasts since the paracrine parameter is negative Hambli et al, 2016 Activation function of preosteoclast differentiation RANK concentration is modified by adding denosumab occupancy term, which reflects denosumab-RANKL binding Marathe et al, 2008 PTH -Preosteoclasts proliferation term -Lining cells differentiation term -Osteoblast apoptosis term -Preosteoclast proliferation and lining cell differentiation terms have been controlled by a function driven by the concentration of PTH and that depends on β-catenin concentration. -β-Catenin concentration depend on Dv1 and Axin-APC-GSK-3 complex -Axin-APC-GSK-3 complex production rate is regulated by PTH -The osteoblast apoptosis rate has been controlled by a function driven by the concentration of PTH and that depends on Bcl-2, CBEB, and Runx2 concentrations.…”

Section: Denosumab Activation Function Of Preosteoclast Differentiationmentioning

confidence: 99%

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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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“…In the work of Hambli et al (2016), denosumab's effect on the bone-specific region, which is the proximal femur of…”

Section: Mathematical Models: Mechanistic Pharmacokinetic/pharmacodynmentioning

confidence: 99%

Section: Denosumab Activation Function Of Preosteoclast Differentiationmentioning

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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show abstract

“…In a fixed volume of carrier solution, the internalization process of nanoparticles was studied. The relationship between the internalization process of nanoparticles and drug concentration (1,5,10, and 20μg/mL) was investigated. The BMMs were incubated with nanoparticles for 4 h. As shown in Figure 6, the fluorescence image and FACS analysis show that nanoparticles with different doses can be effectively internalized, and drugs in nanoparticles can be effectively released in BMMs.…”

Section: Cellular Uptakementioning

confidence: 99%

“…5,6 In recent years, there is evidence suggesting that inhibiting cellular ossification will be the most effective way to treat chronic diseases. [7][8][9][10] With further studies, researchers have developed an oligopeptide that can significantly reduce and inhibit the osteoclastic ability of bone marrowderived macrophages (BMMs), and achieve reduce excessive bone absorption. 11,12 In this study, we designed a drug delivery system that can fully and effectively deliver these molecules to BMMs.…”

Section: Introductionmentioning

confidence: 99%

Thermosensitive nanoparticle of mPEG-PTMC for oligopeptide delivery into osteoclast precursors

Wang

Yang

Liu

et al. 2020

Journal of Bioactive and Compatible Polymers

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Transmembrane delivery of biomolecules through nanoparticles plays an important role in targeted therapy. Here, we designed a simple nanoparticle for the delivery of model peptide drug into primary osteoclast precursor cells (bone marrow macrophages) by thermosensitive and biodegradable diblock copolymer monomethoxy poly(ethylene glycol)-block-poly(trimethylene carbonate). The model peptide drug was encapsulated into the nanoparticle by dropping the drug carrier dissolved in dimethylsulfoxide solvent into water containing poly(vinyl alcohol) to achieve temperature response nanoparticles. Through size analysis, we found that the nanoparticles possessed a temperature-sensitive property between 30°C and 40°C. Moreover, flow cytometry and spectrofluorimetry analysis indicated that nanoparticle systems underwent significant cellular uptake. In addition, the evaluation of cell biology showed that nanoparticles have excellent biocompatibility. Thus, the results indicated that the temperature-sensitive nanoparticles have potential application value for targeted delivery of oligopeptide in the treatment process of osteoarthritis.

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“…A recent study of Hambli et al (2016) showed the ability of a computer model in performing a simulation on the effects of drug treatments and doses on bone volume. This represents a new frontier of prediction of the optimal treatment strategy, allowing a personalization of drug dosing and duration of treatment for a specific patient.…”

Section: Teriparatidementioning

confidence: 99%

Pharmacological Therapy of Osteoporosis: A Systematic Current Review of Literature

et al. 2017

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Osteoporosis is the most common bone disease affecting millions of people worldwide, particularly in elderly or in post-menopausal women. The pathogenesis is useful to understand the possible mechanism of action of anti-osteoporotic drugs. Early diagnosis, possible with several laboratory and instrumental tests, allows a major accuracy in the choice of anti-osteoporosis drugs. Treatment of osteoporosis is strictly related to severity of pathology and consists on prevention of fragility fractures with a correct lifestyle and adequate nutritional supplements, and use of pharmacological therapy, started in patients with osteopenia and history of fragility fracture of the hip or spine. The purpose of this review is to focus on main current pharmacological products to treat osteoporotic patients.

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Prediction of denosumab effects on bone remodeling: A combined pharmacokinetics and finite element modeling

Cited by 25 publications

References 42 publications

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

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

Thermosensitive nanoparticle of mPEG-PTMC for oligopeptide delivery into osteoclast precursors

Pharmacological Therapy of Osteoporosis: A Systematic Current Review of Literature

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