ArticleInternational journal for numerical methods in biomedical engineering2014
Mathematical modeling of postmenopausal osteoporosis and its treatment by the anti-catabolic drug denosumab.
Article in International journal for numerical methods in biomedical engineering, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Clinical Data for Parametrization ofFrontiers in bioengineering and biotechnology · 2022Pooled it
- Mechanobiological Response of Osteocyte TRPV4 Base on the Piezoelectricity of Bone Matrix.Annals of biomedical engineering · 2026Article
- Mathematical modeling of bone remodeling after surgical menopause.Frontiers in systems biology · 2026Article
- An in silico approach to elucidate the pathways leading to primary osteoporosis: age-related vs. postmenopausal.Biomechanics and modeling in mechanobiology · 2024Article
- Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types.eLife · 2022Article
- Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts.Frontiers in bioengineering and biotechnology · 2022Review
- Assessment of Strategies for Safe Drug Discontinuation and Transition of Denosumab Treatment in PMO-Insights From a Mechanistic PK/PD Model of Bone Turnover.Frontiers in bioengineering and biotechnology · 2022Article
- Combined Effects of Exercise and Denosumab Treatment on Local Failure in Post-menopausal Osteoporosis-Insights from Bone Remodelling Simulations Accounting for Mineralisation and Damage.Frontiers in bioengineering and biotechnology · 2021Article
- Modelling Human Locomotion to Inform Exercise Prescription for Osteoporosis.Current osteoporosis reports · 2020Review
- Toward a Mathematical Modeling of Diseases' Impact on Bone Remodeling: Technical Review.Frontiers in bioengineering and biotechnology · 2020Review
- The Effectiveness and Safety of Acupoint Catgut Embedding for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis.Evidence-based complementary and alternative medicine : eCAM · 2019Review
- Automated Scale Reduction of Nonlinear QSP Models With an Illustrative Application to a Bone Biology System.CPT: pharmacometrics & systems pharmacology · 2018Article
- Multiscale modeling methods in biomechanics.Wiley interdisciplinary reviews. Systems biology and medicine · 2017Review
- Poromicromechanics reveals that physiological bone strains induce osteocyte-stimulating lacunar pressure.Biomechanics and modeling in mechanobiology · 2016Article
- Regenerative orthopaedics: in vitro, in vivo...in silico.International orthopaedics · 2014Review
- Changes in the degree of mineralization with osteoporosis and its treatment.Current osteoporosis reports · 2014Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Denosumab, a fully human monoclonal antibody, has been approved for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab rests on its ability to inhibit osteoclast differentiation. Here, we present a computational approach on the basis of coupling a pharmacokinetics model of denosumab with a pharmacodynamics model for quantifying the effect of denosumab on bone remodeling. The pharmacodynamics model comprises an integrated systems biology-continuum micromechanics approach, including a bone cell population model, considering the governing biochemical factors of bone remodeling (including the action of denosumab), and a multiscale micromechanics-based bone mechanics model, for implementing the mechanobiology of bone remodeling in our model. Numerical studies of postmenopausal osteoporosis show that denosumab suppresses osteoclast differentiation, thus strongly curtailing bone resorption. Simulation results also suggest that denosumab may trigger a short-term bone volume gain, which is, however, followed by constant or decreasing bone volume. This evolution is accompanied by a dramatic decrease of the bone turnover rate by more than one order of magnitude. The latter proposes dominant occurrence of secondary mineralization (which is not anymore impeded through cellular activity), leading to higher mineral concentration per bone volume. This explains the overall higher bone mineral density observed in denosumab-related clinical studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.