SynthesisClinical pharmacokinetics2011
Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis.
Synthesis in Clinical pharmacokinetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
63 citing papers in PubMed, 116 citations in OpenAlex.
- A Randomized Phase 1 Study Comparing the PK, PD, Safety, and Immunogenicity of Proposed Biosimilar RGB-14-X and Denosumab in Healthy Adult Males.Clinical and translational science · 2026Trial
- No overshoot of bone turnover after withdrawal of denosumab treatment of adults with Langerhans cell histiocytosis: a prospective clinical trial.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Trial
- Population Pharmacokinetics of Epcoritamab Following Subcutaneous Administration in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.Clinical pharmacokinetics · 2025Trial
- MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects.Clinical and translational science · 2024Trial
- Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Trial
- Phase I, Randomized, Placebo-Controlled, Dose-Escalation Study of GB223, a Fully-Humanized Monoclonal Antibody to RANKL, in Healthy Chinese Adults.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Trial
- Pharmacokinetic and pharmacodynamic relationship of AMG 811, an anti-IFN-γ IgG1 monoclonal antibody, in patients with systemic lupus erythematosus.Pharmaceutical research · 2015Trial
- Body weight predicts denosumab pharmacodynamic duration: a real-world longitudinal cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Article
- The therapeutic window: timing dentoalveolar surgery to minimize MRONJ risk in denosumab-treated osteoporotic patients.JBMR plus · 2026Article
- Pharmacokinetics and pharmacodynamics of the denosumab biosimilar FKS518 and reference denosumab in healthy subjects: the Lumiade-1 study.JBMR plus · 2026Article
- Nipocalimab Dose Selection in Generalized Myasthenia Gravis.CPT: pharmacometrics & systems pharmacology · 2025Article
- Article
- Personalizing denosumab therapy in postmenopausal Indian women with osteoporosis: predictive role of bone turnover markers and body mass index in determining dosing interval.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Observational
- Enhancing viral dynamics modeling: reliable initial estimation and validity conditions for quasi-steady state approximation (QSSA).BMC biology · 2025Article
- Population PK Modeling of Denosumab Biosimilar MB09 and Reference Denosumab to Establish PK Similarity.Pharmaceutics · 2025Article
- Effect of anti-resorptive therapy on implant failure: a systematic review and meta-analysis.Journal of periodontal & implant science · 2025Review
- Risk assessment and drug interruption guidelines for dentoalveolar surgery in patients with osteoporosis receiving anti-resorptive therapy.Journal of dental sciences · 2025Review
- Population pharmacokinetics/pharmacodynamics analysis confirming biosimilarity of SB16 to reference denosumab.Frontiers in pharmacology · 2025Article
- Validity conditions of approximations for a target-mediated drug disposition model: A novel first-order approximation and its comparison to other approximations.PLoS computational biology · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveInhibition of the receptor activator of nuclear factor κ-B ligand (RANKL) is a therapeutic target for treatment of bone disorders associated with increased bone resorption, such as osteoporosis. The objective of this analysis was to characterize the population pharmacokinetics of denosumab (AMG 162; Prolia®), a fully human IgG2 monoclonal antibody that binds to RANKL, in healthy subjects and postmenopausal women with osteopenia or osteoporosis.
methodsA total of 22944 serum free denosumab concentrations from 495 healthy subjects and 1069 postmenopausal women with osteopenia or osteoporosis were pooled. Denosumab was administered as either a single intravenous dose (n = 36), a single subcutaneous dose (n = 469) or multiple subcutaneous doses (n = 1059), ranging from 0.01 to 3 mg/kg (or 6-210 mg as fixed mass dosages), every 3 or 6 months for up to 48 months. An open, two-compartment pharmacokinetic model with a quasi-steady-state approximation of the target-mediated drug disposition model was used to describe denosumab pharmacokinetics, using NONMEM Version 7.1.0 software. Subcutaneous absorption was characterized by the first-order absorption rate constant (k(a)), with constant absolute bioavailability over the range of doses that were evaluated. Clearance and volume of distribution parameters were scaled by body weight, using a power model. Model evaluation was performed through visual predictive checks.
resultsThe subcutaneous bioavailability of denosumab was 64%, and the k(a) was 0.00883 h-1. The central volume of distribution and linear clearance were 2.49 L/66 kg and 3.06 mL/h/66 kg, respectively. The baseline RANKL level, quasi-steady-state constant and RANKL degradation rate were 614 ng/mL, 138 ng/mL and 0.00148 h-1, respectively. Between-subject variability in model parameters was moderate. A fixed dose of 60 mg provided RANKL inhibition similar to that achieved by equivalent body weight-based dosing. The effects of age and race on the area under the serum concentration-time curve of denosumab were less than 15% over the range of covariate values that were evaluated.
conclusionsThe non-linearity in denosumab pharmacokinetics is probably due to RANKL binding, and denosumab dose adjustment based on the patient demographics is not warranted.
Indexed as
Identifiers
What OpenQuestion holds
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.