STOCHASTIC AND STRAIN-WEIGHTED SIMULATIONS OF CANCELLOUS BONE REMODELLING: SIMULATION RULES AND PARAMETERS G SISIAS 1 , CA DOBSON 2 , R PHILLIPS 3 , MJ FAGAN 2 and CM LANGTON 4 1 Department of Computing, School of Informatics, University of Bradford, Bradford, UK 2 School of Engineering, University of Hull, Hull, UK 3 Department of Computer Science, University of Hull, Hull, UK 4 Centre for Metabolic Bone Diseases, University of Hull and Hull and East Yorkshire Hospitals NHS Trust, UK Abstract: Bone has well-defined structural and morphological properties, as well as cellular processes based on stimuli that control activity at microscopic level. Simulations that can take into account the above and can operate on real bone can be used to investigate scenarios such as normal age-related loss of bone, loss of bone due to disuse or osteoporosis or virtual drug treatment. The aim of this work is to define a set of simulation rules such that the cellular processes of bone can be modelled and used in scenarios that investigate bone remodelling and the effects on its mechanical properties. Keywords: Simulation, cancellous bone, remodelling, stochastic, strain-weighted. 1. INTRODUCTION Bone tissue consists of calcium hydroxyapatite mineral absorbed onto a collagen matrix. Throughout life there is a process of remodelling, where old bone is removed by osteoclast cells and new collagen fibres are laid down by osteoblast cells. This is under the control of physical activity and several hormones. There are two types of bone structure, cortical and cancellous. Cortical bone is predominantly solid and makes up the shafts of the long bones in the skeleton. Cancellous bone has a porous structure made up of an array of trabecular bone fibres interspersed with bone marrow, and is found near the joint surfaces of the long bones and within the individual vertebrae making up the spinal column. Bone grows under body forces and the trabecular fibres follow the principal lines of stress, as can be clearly seen, for example, in a cross-section of the hip. 2. BONE PATHOPHYSIOLOGY The main responsibilities of bones are to withstand the mechanical forces exerted to them by muscles or gravity, protect the vital organs from possible damage, and provide a reserve of minerals such as calcium or phosphate to the body. Most bones are composed of a dense outer shell of cortical bone surrounding the central porous cancellous (trabecular) bone. Cancellous bone can be considered to be a cellular structure, consisting of an interconnecting 3D network of thin bars (trabeculae) interspersed with marrow, connective tissue and blood vessels (Baron 1993), with the porosity of cancellous bone typically ranging from 30% up to 95% (Gibson and Ashby 1988). From birth to maturity, healthy humans exhibit an increase in bone mass of about 40 times. The peak of bone mass as result of growth is reached between the ages 20-30, and bone mass starts decreasing around ages 30-40, while by the age of 70 more than 30% of the original peak bone mass is lost. This long-term bone loss is temporarily accelerated on women after menopause, but after a few years this acceleration stops. This process of old bone replaced by new one is also known as bone remodeling. The phases of the remodeling process are resorption, reversal, formation and quiescence, and last totally about 180- 200 days. The main two types of cells responsible for the remodeling process are osteoblasts and osteoclasts. Osteoblastic cells are responsible for the production of the material for reposition (e.g. collagen) and are not normally found alone, but in groups of about 100-400, forming a bone reposition site. On the other hand osteoclasts are responsible for the resorption of bone, and are usually found in groups of 1-2 or even 4-5 cells. Such a group of similar type of cells is also known as a BMU, or a basic multi- cellular unit.