title: Disease Systems Analysis of Bone Mineral Density and Bone Turnover Markers in Response to Alendronate, Placebo, and Washout in Postmenopausal Women.
abstract: A previously established mechanism-based disease systems model for osteoporosis that is based on a mathematically reduced version of a model describing the interactions between osteoclast (bone removing) and osteoblast (bone forming) cells in bone remodeling has been applied to clinical data from women (n = 1,379) receiving different doses and treatment regimens of alendronate, placebo, and washout. The changes in the biomarkers, plasma bone-specific alkaline phosphatase activity (BSAP), urinary N-telopeptide (NTX), lumbar spine bone mineral density (BMD), and total hip BMD, were linked to the underlying mechanistic core of the model. The final model gave an accurate description of all four biomarkers for the different treatments. Simulations were used to visualize the dynamics of the underlying network and the natural disease progression upon alendronate treatment and discontinuation. These results complement the previous applications of this mechanism-based disease systems model to data from various treatments for osteoporosis.
authors.affiliation: Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands.|Leiden Academic Centre for Drug Research, Division of Pharmacology, Leiden, The Netherlands.|Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Berkhout
authors.affiliation: Merck Sharp & Dohme Corp., Kenilworth, New Jersey, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Stone
authors.affiliation: Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: Verhamme
authors.affiliation: Leiden Academic Centre for Drug Research, Division of Pharmacology, Leiden, The Netherlands.|Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Danhof
authors.affiliation: Leiden Academic Centre for Drug Research, Division of Pharmacology, Leiden, The Netherlands.|Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: Post
mesh_terms: D019386:Alendronate / Q000008:administration & dosage* / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000032:analysis*; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D024042:Collagen Type I / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010455:Peptides / Q000652:urine; D049490:Systems Biology / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; D019386:Alendronate