**1.1. Cells activity in bone**

Bone tissue is the component of the skeletal system supporting human body. Bone structure is continuously renewed by remodeling, that is, the alternately-repeated events of local bone resorption and formation. Three mature cell types of osteoblasts, osteoclasts and osteocytes play crucial roles in bone remodeling process. Bone metabolism is regulated by bone cells which respond to various environmental signals coming from chemical, magnetic, electrical and mechanical stimuli (Klein-Nulend et al., 2005).

Osteoblast are bone forming cells that synthesize and secrete bone matrix, participate in the calcification and formation of bone, and regulate the flux of calcium and phosphate in and

© 2012 Kwon et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Kwon et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

out of bone. Osteoclasts are multinucleated giant cells; their role is to resorb bone. Actively resorbing osteoclasts are usually found in cavities on bone surfaces, called resorption cavities. Osteocytes are the most abundant cell type in mature bone. During bone formation some osteoblasts are left behind in the newly formed osteoid as osteocytes when the bone formation moves on. The embedded osteoblast in lacunae differentiate into osteocytes by losing much of their organelles but acquiring long, slender processes encased in the lacunarcanulicular network that allow contact with earlier incorporated osteocytes and with osteoblast and bone lining and periosteal cells lining the bone surface and the vasculature. The osteocytes are the cells best placed to sense the magnitude and distribution of strains. They are strategically placed both to respond to changes in mechanical strain and to disseminate fluid flow to transduce information to surface cells of the osteoblastic lineage via their network of canalicular processes and communicating gap junctions (Cowin, 2001).

Osteocyte Apoptosis-Induced Bone Resorption

in Mechanical Remodeling Simulation – Computational Model for Trabecular Bone Structure 27

It is well recognized that the origin of osteocyte is osteoblasts embedded in its own matrix and some osteocytes die eventually (apoptosis). Aging, loss of estrogen, loading, and chronic glucocorticoid administration is known to increase osteocyte apoptosis and loading decreases the proportion of apoptotic osteocyte in cortical bone in rats (Noble et al., 2003; Gu et al., 2005; Delgado-Calle et al., 2011; Kennedy et al., 2012). These studies investigated the role of osteocytes in the control of loading related remodeling and they exhibited the effects on osteocyte viability of mechanical loading applied to the bone. Osteocyte apoptosis triggers osteoclast precursor recruitment to initiate bone resorption, whether it is induced by weightlessness or fatigue loading and precedes osteoclast resorption. An osteoclast/osteoblastdependent process related on the osteocytes population may participate in making the decision as to where and when a new remodeling cycle will be initiated. That is, osteocyte network could be considered the main sensor of loads. To take these observations into account, Frost proposed the concept of mechanostat (Duncan & Turner, 1995; Frost, 2003; Hughes et al., 2010). According to this concept, the authors have proposed the mathematical model for bone

To develop the computer simulation model of bone remodeling considering bone metabolism macroscopically, this section describes the bone remodeling model referring to the strainbased mechanostat theory submitted by Harold Frost and refined more than 5 decades. Physiological, low, and high strain ranges were defined in mechanostat theory, and different mechanisms were considered to describe the mechanical surface remodeling of trabecular

The following was assumed as the result of a remodeling turnover for each strain range: 1) in the physiological strain range, the occurrence of bone resorption or formation depends on the degree of the local stress non-uniformity; 2) in the low strain range, only bone resorption occurs owing to osteocyte apoptosis and its frequency increases with decreasing strain; 3) in the high strain range, only bone formation occurs by targeted remodeling and its frequency increases with strain. Each window is distinguished by threshold values of equivalent strain *ε<sup>c</sup>* in the context of the mechanostat theory, and low, physiological, and high strain range correspond to the strain ranges of *εc* smaller than *εdu*, between *εpl* - *εpu* and larger than *εol* (Fig 1).

Trabecular architecture is discretized using voxel finite elements, as schematically shown in Fig. 2. The trabecular surface movement by remodeling is expressed by adding and removing voxel elements on the surface according to the mechanical stress/strain conditions determined by a finite element analysis. Each trabecular element was classified by equivalent strain into low, physiological, and high strain range. Bone surface remodeling was assumed to occur according to the mathematical models of each window described in the following

**1.3. Mechanical stimuli and osteocyte apoptosis** 

remodeling described in the following section.

architecture resulting in the structural change (Kwon et al., 2010a).

**2. Bone remodeling simulation** 

sections in detail.
