Computer model of endochondral growth and ossification in long bones: Biological and mechanobiological influences

Endochondral growth and ossification, the processes by which cartilage incr eases in size and is replaced by bone, are affected by biological factors s uch as intrinsic genetic makeup and systemic chemical agents. In addition, these processes are affected by epigenetic mechanical factors: they may be accelerated in regions of intermittent high shear stress and decelerated in regions of intermittent high hydrostatic pressure. Previous models of bone development have not incorporated both biological and mechanobiological in fluences on endochondral growth and ossification. We have implemented a fin ite element analysis to model a developing bone rudiment from 8 weeks of ge stational development to approximately 2 years after birth. As a function o f time, we calculated a maturity index that reflects the progression of a r egion of cartilage through the endochondral ossification sequence of prolif eration, hypertrophy, mineralization, and replacement by bone. We calculate d a specific growth rate for each region of cartilage and estimated overall longitudinal growth of the rudiment. Regions of cartilage replaced by bone were remodeled. The results from the maturity index can be compared with d istributions of proliferative, hypertrophic. and mineralized cartilage seen on histology at various stages in development. The results of the simulati on predicted prenatal and postnatal developmental events, including formati on of a secondary ossific nucleus, a layer of articular cartilage, and a gr owth plate. Our results demonstrate the necessity to include biological and mechanobiological influences when endochondral growth and ossification are considered.