title: Patient-specific bone modelling and remodelling simulation of hypoparathyroidism based on human iliac crest biopsies.
abstract: We previously developed a load-adaptive bone modelling and remodelling simulation model that can predict changes in the bone micro-architecture as a result of changes in mechanical loading or cell activity. In combination with a novel algorithm to estimate loading conditions, this offers the possibility for patient-specific predictions of bone modelling and remodelling. Based on such models, the underlying mechanisms of bone diseases and/or the effects of certain drugs and their influence on the bone micro-architecture can be investigated. In the present study we test the ability of this approach to predict changes in bone micro-architecture during hypoparathyroidism (HypoPT), as an illustrative example. We hypothesize that, apart from reducing bone turnover, HypoPT must also lead to increased osteocyte mechanosensitivity in order to explain the changes in bone mass seen in patients. Healthy human iliac crest biopsies were used as the starting point for the simulations that mimic HypoPT conditions and the resultant micro-architectures were compared to age-matched clinical HypoPT biopsies. Simulation results were in good agreement with the clinical data when osteocyte mechanosensitivity was increased by 40%. In conclusion, the results confirm our hypothesis, and also demonstrate that patient-specific bone modelling and remodelling simulations are feasible.
authors.affiliation: Eindhoven University of Technology, Department of Biomedical Engineering, Orthopaedic Biomechanics, PO Box 513, 5600 MB Eindhoven, The Netherlands. p.christen@tue.nl
authors.forename: Patrik
authors.initials: P
authors.lastname: Christen
authors.forename: Keita
authors.initials: K
authors.lastname: Ito
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.forename: Mishaela R
authors.initials: MR
authors.lastname: Rubin
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
authors.forename: Bert
authors.initials: B
authors.lastname: van Rietbergen
mesh_terms: D000368:Aged; D000465:Algorithms; D001706:Biopsy; D015519:Bone Density; D016723:Bone Remodeling; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007085:Ilium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D040542:Mechanotransduction, Cellular; D008875:Middle Aged; D008954:Models, Biological; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology