Mechanical conditions determine the geometry of the epiphysis

Introduction: Fetal long-bone growth is the result of growth and subsequent mineralization of the cartilaginous epiphyses. Prior to mineralization, the shapes of the epiphyses determine the geometries of the proximal and distal ends of long bones, including joint shapes and prominences which are important for bone functioning. It is unclear how morphogenesis of the epiphyses is controlled. Various developmental studies suggest that biochemical control and mechanical loading are both involved. We aim to study using a numerical approach the hypothesis that fetal bone growth is growth-factor controlled, while external mechanical loading determines the morphology of the epiphysis. Methods: We previously developed a 1D bone-growth model in which epiphysis development was selectively controlled by the growth factors Indian hedgehog (Ihh), PTHrP and VEGF [1]. This approach was extended to 2D and implemented in Abaqus. A 2D mesh of a 16-days old anlage of a mouse metatarsal bone is used as the initial geometry. It only consists of cartilage and is not yet mineralized. We simulate growth over several days during which the cartilage grows and mineralizes, controlled by PTHrP, Ihh and VEGF. Simulations are performed with and without the presence of additional external loading. Experimentally observed shapes of metatarsal bones at embryonic day 19 are compared with simulation results for validation. Results: The computed geometry compares well with the geometry of a mouse metatarsal bone at embryonic day 19. Without external mechanical loading the epiphysis develops a circular, non-physiological geometry. The mechanical environment significantly influences the geometry of the epiphysis. Discussion: External mechanical forces importantly determine the shape of the epiphysis during development, and drive bone morphology to a physiological geometry. These external forces may arise from muscle contractions as well as from tensile forces which develop during growth due to stretching of tendons, ligaments, periosteum and perichondrium. It is challenging to determine the relative importance of these structures to eventual bone morphogenesis.