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23-27 oktober 2006 Vitenskapelige forhandlinger Abstrakt nr: 229<br />

MECHANICAL CONDITIONS DETERMINE THE GEOMETRY OF THE<br />

EPIPHYSIS<br />

Huiskes R, Braam S, Foolen J, van Donkelaar R<br />

Eindhoven University of Technology, Dept Biomedical Engineering<br />

Den Dolech 2, WH 4.131, PO Box 513, 5600 MB Eindhoven, The Netherlands<br />

Introduction: Fetal long-bone growth is the result of growth and subsequent mineralization of<br />

the cartilaginous epiphyses. Hence, the shapes of the epiphyses determine the geometries of<br />

the proximal and distal ends of long bones prior to bone remodeling. These regions contain<br />

many bony prominences which are important for bone functioning. It is unclear how<br />

morphogenesis of the epiphyses is controlled. Various developmental studies suggest that<br />

biochemical control processes and mechanical loading are both involved.<br />

We previously developed a 1D bone-growth model in which epiphysis development is<br />

controlled by the growth factors Indian hedgehog (Ihh), PTHrP and VEGF. The present study<br />

uses this finite element model to assess the effect of additional externally applied mechanical<br />

loading on the morphogenesis of the epiphysis.<br />

Methods: A 2D representation of a 16-days old anlage of a mouse metatarsal bone is used as<br />

the initial geometry in our finite element model of fetal bone development. This anlage only<br />

consists of cartilage and is not yet mineralized. We simulate bone development over several<br />

days during which the cartilage grows and mineralizes. This process is fully controlled by<br />

PTHrP, Ihh and VEGF. First, the computed and experimentally observed shapes of metatarsal<br />

bones at embryonic day 19 are compared for validation. Subsequently, two extended<br />

simulations are performed, one with and one without the presence of additional external<br />

loading.<br />

Results: The computed geometry compares well with the geometry of a mouse metatarsal<br />

bone at embryonic day 19. Without external mechanical loading in the extended simulation,<br />

the epiphysis develops a circular, non-physiological geometry. Both the application of<br />

mechanical constraints against growth and tensile forces during growth, significantly<br />

influence the geometry of the epiphysis.<br />

Discussion: External mechanical forces importantly determine the shape of the epiphysis<br />

during development. These forces drive bone morphology to a physiological geometry.<br />

External mechanical forces may arise from muscle contractions as well as from tensile forces<br />

which develop during growth due to stretching of tendons, ligaments, periosteum and<br />

perichondrium. It is challenging to determine the relative importance of these structures to<br />

eventual bone morphogenesis.

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