R Ronald Ruimerman

Effects of mechanical forces on maintenance and adaptation of form in trabecular bone

The architecture of trabecular bone, the porous bone found in the spine and at articulating joints, provides the requirements for optimal load transfer, by pairing suitable strength and stiffness to minimal weight according to rules of mathematical design. But, as it is unlikely that the architecture is fully pre-programmed in the genes, how are the bone cells informed about these rules, which so obviously dictate architecture? A relationship exists between bone architecture and mechanical usage—while strenuous exercise increases bone mass, disuse, as in microgravity and inactivity, reduces it. Bone resorption cells (osteoclasts) and bone formation cells (osteoblasts) normally balance bone mass in a coupled homeostatic process of remodelling, which renews some 25% of trabecular bone volume per year. Here we present a computational model of the metabolic process in bone that confirms that cell coupling is governed by feedback from mechanical load transfer.This model can explain the emergence and maintenance of trabecular architecture as an optimal mechanical structure, as well as its adaptation to alternative external loads.

The Effects of Trabecular-Bone Loading Variables on the Surface Signaling Potential for Bone Remodeling and Adaptation

It is widely believed that mechanical forces affect trabecular bone structure and orientation. The cellular mechanisms involved in this relationship, however, are poorly understood. In earlier work we developed a theoretical, computational framework, coupling bone-cell metabolic expressions to the local mechanical effects of external bone loading. This theory is based on the assumption that osteocytes within the bone tissue control the recruitment of bone-resorbing osteoclasts and bone-forming osteoblasts, by sending strain-energy-density (SED) related signals to trabecular surfaces through the osteocytic, canalicular network. The theory explains the known morphological effects of external bone-loading variations in magnitude and frequency. It also explains the development of osteoporosis, as an effect of increased osteoclast resorption due to estrogen deficiency in postmenopausal women, and to reduced physical activity levels in general. However, the theory uses lumped variables to represent the mechanisms of osteocyte mechano-sensing and signaling. The question is whether these mechanisms could not be specified in a more realistic way. On the one hand, anabolic osteocyte signals might be triggered by the local mechanical loading variables they experience directly, as we assumed in our original theory. On the other hand, osteocyte signals might be triggered by fluid flow in the osteocytic network at large, as was suggested by others. For that purpose we compared the effects of SED, maximal principal strain and volumetric strain as representing local loading variables, to their spatial gradients on the morphological predictions of our computational model. We found that, in concept, they all produced reasonable trabecular structures. However, the predicted trabecular morphologies based on SED as the triggering variable were more realistic in dimensions and relevant metabolic parameters.

A computer-simulation model relating bone-cell metabolism to mechanical adaptation of trabecular architecture

The architecture of trabecular bone is thought to be an optimal mechanical structure in terms of maximal strength and stiffness, and minimal weight. The structural optimality seems to be maintained during growth and adulthood by adaptation of mass and structure through a relationship with actual mechanical usage. The formation and maintenance of the architecture is realized by bone-resorbing osteoclasts and bone-forming osteoblasts, the effector cells of bone metabolism. Hence, a feedback regulatory mechanism between external load and metabolism must exist. We have developed an FEA-based computer-simulation model to study explanations for the workings of such regulatory schemes (1: Huiskes et al. (2000), Nature, 404, 704-706). The model is based on a mechanosensory function of osteocytes, which are thought to react to the local strain-energy-density rate in the mineralized tissue, produced by dynamic external loading on the bone. As an effect of this signal, osteocytes are assumed to transfer an osteoblast recruitment stimulus to the surface, enhancing bone formation. Osteoclasts are assumed to resorb bone that is disused or damaged, in a spatially random manner. This model provides an explanation for the maintenance and adaptation of trabecular bone architecture as an optimal structure. In this article, the mathematical background of the model is specified.

Development of a unifying theory for mechanical adaptation and maintenance of trabecular bone

Trabecular bone is a tissue with a complex 3D structure, consisting of struts and plates, which attains its mature morphology during growth in a process called ‘modeling’. In maturity, the tissue is renewed continuously by local bone resorption and subsequent formation in a process called ‘remodeling’. Both these metabolic activities are executed by bone-resorbing osteoclastic and bone-forming osteoblastic cells. It is known that bone mass and trabecular orientation are adapted to the external forces and that alternative loading conditions lead to adaptations of the internal tissue architecture. The question is how the characteristics of external loads are sensed in the bone, and how they are translated to structural adaptation of the tissue. The time scale of the underlying processes is on the order of months, or even years. This aspect makes bone a complex research topic. In this paper, we discuss the application of computer simulation to investigate the remarkable adaptive processes. We describe our developments of empirical models in the past 15 years, able to predict bone adaptation to external loads from a macroscopic level towards a cell-based level, in which the most important relationships of the cellular processes are captured. The latest model explains the morphological phenomena observed in trabecular bone at a microscopic level.

RELATING OSTEON DIAMETER TO STRAIN

Article history: Osteon diameter is generall Received 14 December 2007 Revised 24 April 2008 Accepted 10 May 2008 Available online 28 May 2008 Edited by: David Burr