Show simple item record

dc.contributor.authorTrichilo, S
dc.contributor.authorScheiner, S
dc.contributor.authorForwood, M
dc.contributor.authorCooper, DML
dc.contributor.authorPivonka, P
dc.date.accessioned2019-07-06T12:31:41Z
dc.date.available2019-07-06T12:31:41Z
dc.date.issued2019
dc.identifier.issn0022-5193
dc.identifier.doi10.1016/j.jtbi.2019.04.020
dc.identifier.urihttp://hdl.handle.net/10072/385062
dc.description.abstractThis paper presents a pharmacokinetic/pharmacodynamic (PK/PD) model of the action of PTH(1-34) on bone modelling and remodelling, developed for quantitatively investigating the dose- and administration pattern-dependency of the bone tissue response to this drug. Firstly, a PK model of PTH(1-34) was developed, accounting for administration via subcutaneous injections. Subsequently, the PK model was coupled to a (mechanistic) bone cell population model of bone modelling and remodelling, taking into account the effects of PTH(1-34) on the differentiation of lining cells into active osteoblasts, on the apoptosis of active osteoblasts, and on proliferation of osteoblast precursors, as well as on the key regulatory pathways of bone cell activities. Numerical simulations show that the coupled PK/PD model is able to distinguish between continuous and intermittent administration patterns of PTH(1-34), in terms of yielding both catabolic bone responses (if drug administration is carried out continuously) and anabolic bone responses (if drug administration is carried out intermittently). The model also features a non-linear relation between bone gain and drug dose (as known from experiments); doubling the dose from 80 g/kg/day to 160 g/kg/day induced a 1.3-fold increase of the bone volume-to-total volume ratio. Furthermore, the model presented in this paper confirmed that bone modelling represents an essential mechanism of the anabolic response of bone to PTH(1–34) administration in rat models, and that the large amount of bone formation observed in such models cannot be explained via remodelling alone.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofpagefrom67
dc.relation.ispartofpageto79
dc.relation.ispartofjournalJournal of Theoretical Biology
dc.relation.ispartofvolume473
dc.subject.fieldofresearchMathematical Sciences
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchInformation and Computing Sciences
dc.subject.fieldofresearchcode01
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode08
dc.titleComputational model of the dual action of PTH — Application to a rat model of osteoporosis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2019 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorForwood, Mark R.


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record