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

Endochondral growth and ossification, the processes by which cartilage increases in size and is replaced by bone, are affected by biological factors such 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 influences on endochondral growth and ossification. We have implemented a finite element analysis to model a developing bone rudiment from 8 weeks of gestational development to approximately 2 years after birth. As a function of time, we calculated a maturity index that reflects the progression of a region of cartilage through the endochondral ossification sequence of proliferation, hypertrophy, mineralization, and replacement by bone. We calculated 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 distributions of proliferative, hypertrophic, and mineralized cartilage seen on histology at various stages in development. The results of the simulation predicted prenatal and postnatal developmental events, including formation of a secondary ossific nucleus, a layer of articular cartilage, and a growth plate. Our results demonstrate the necessity to include biological and mechanobiological influences when endochondral growth and ossification are considered.