Trial reportBiopharmaceutics & drug disposition2011
Integrated model for denosumab and ibandronate pharmacodynamics in postmenopausal women.
Trial report in Biopharmaceutics & drug disposition, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Modeling and simulation of bone mineral density in Japanese osteoporosis patients treated with zoledronic acid using tartrate-resistant acid phosphatase 5b, a bone resorption marker.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2018Trial
- Disease Systems Analysis of Bone Mineral Density and Bone Turnover Markers in Response to Alendronate, Placebo, and Washout in Postmenopausal Women.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Application of a mechanism-based disease systems model for osteoporosis to clinical data.Journal of pharmacokinetics and pharmacodynamics · 2013Trial
- Population PK Modeling of Denosumab Biosimilar MB09 and Reference Denosumab to Establish PK Similarity.Pharmaceutics · 2025Article
- Population pharmacokinetics/pharmacodynamics analysis confirming biosimilarity of SB16 to reference denosumab.Frontiers in pharmacology · 2025Article
- A review of mathematical modeling of bone remodeling from a systems biology perspective.Frontiers in systems biology · 2024Article
- Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types.eLife · 2022Article
- 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
- On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model.Scientific reports · 2021Article
- Review
- 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
- Translational Quantitative Systems Pharmacology in Drug Development: from Current Landscape to Good Practices.The AAPS journal · 2019Review
- Osteoblasts are "educated" by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment.Breast cancer research : BCR · 2019Article
- Automated Scale Reduction of Nonlinear QSP Models With an Illustrative Application to a Bone Biology System.CPT: pharmacometrics & systems pharmacology · 2018Article
- Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.Cancers · 2018Review
- Application of a Systems Pharmacology-Based Placebo Population Model to Analyze Long-Term Data of Postmenopausal Osteoporosis.CPT: pharmacometrics & systems pharmacology · 2015Article
- A semi-mechanistic model of bone mineral density and bone turnover based on a circular model of bone remodeling.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Using early biomarker data to predict long-term bone mineral density: application of semi-mechanistic bone cycle model on denosumab data.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- HIF targets in bone remodeling and metastatic disease.Pharmacology & therapeutics · 2015Review
- Effects of ibandronate sodium, a nitrogen-containing bisphosphonate, on intermediate-conductance calcium-activated potassium channels in osteoclast precursor cells (RAW 264.7).The Journal of membrane biology · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
This study aims to characterize the pharmacodynamic properties of denosumab, a RANK ligand inhibitor, and ibandronate, a bisphosphonate, using an integrated bone homeostasis model in postmenopausal women. Mean temporal profiles of denosumab, serum and urine N-telopeptide (sNTX, uNTX), lumbar spine bone mineral density (BMD) following denosumab administration, and urine C-telopeptide (uCTX) and lumbar spine BMD upon ibandronate administration were extracted from the literature. A mechanistic model was developed that integrates denosumab pharmacokinetics with binding to RANK ligand and ibandronate inhibition of osteoclast precursor differentiation to active osteoclasts (AOC). Biomarker concentrations were linked to the AOC pool. The BMD was characterized by a turnover model with stimulation of bone formation and degradation by AOB (active osteoblasts) and AOC pools. The estimated basal sNTX, uNTX and uCTX concentrations were 7.24 nm, 14.4 nmol/mmolCr and 31µg/mmolCr. The BMD degradation rate was 0.00161 day(-1) with stimulation constants associated with AOB and AOC of 1214 and 790 pm(-1) . The plasma ibandronate concentration producing 50% of maximum inhibition of osteoclast differentiation was 522 ng/l. The integrated model, which incorporates multiple pathways of therapeutic intervention, quantitatively describes changes in clinical biomarkers of bone turnover and BMD after denosumab and ibandronate exposures in postmenopausal women.
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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.