Effect of Mechanical Set Point of Bone Cells on Mechanical Control of Trabecular Bone Architecture

doi:10.1016/S8756-3282(97)00251-2

Bone

Volume 22, Issue 2, February 1998, Pages 125-131

https://doi.org/10.1016/S8756-3282(97)00251-2 Get rights and content

Abstract

The architecture of trabecular bone is thought to be controlled by mechanosensitive bone cells, where hormones provide a background for their responses to mechanical signals. It has been suggested that, in osteoporosis, this response is hampered by changed hormonal levels, thereby increasing the mechanical set point of the cells, which would lead to bone loss. We have investigated if a temporary increase of the mechanical set point causes deterioration of trabecular bone architecture, such as seen in osteoporosis. Furthermore, the effects of a changed loading pattern were investigated for the same reason. For this purpose, we used a computer simulation model, which was based on the regulation of bone architecture by mechanosensitive osteocytes. It was found that a temporary shift of the mechanical set point causes no lasting changes in architecture. Although an increase of the mechanical set point induces bone loss, the mechanism of bone loss (trabecular thinning) differs from what is observed in osteoporosis (loss of whole trabeculae). Hence, a change of the mechanical set point alone cannot explain bone loss as seen in osteoporosis. On the other hand, the removal of load components in a particular direction resulted in irreversible loss of whole trabeculae. These results indicate that such temporary changes in loading patterns could be important risk factors for osteoporosis.

Introduction

The architecture of trabecular bone is thought to be related to the mechanical loads to which it is subjected. This balance between bone architecture and mechanical loading is a dynamic one, where bone is constantly being resorbed and new bone is formed. In osteoporosis, however, bone is inadequately maintained, leading to inferior quality of bone architecture and osteopenia.15, 30Because the normal regulation of bone turnover is complex, with many factors involved, the causes for bone deterioration are unclear. Rodan[36]summarized its essence as a process controlled by mechanical loading in an hormonal environment. Yet, the precise role of mechanical factors in the process of bone remodeling is unclear.

In previous studies, we investigated the effects of mechanical factors on trabecular bone architecture, using computer simulation models.26, 27, 43We assumed that bone turnover is controlled locally by mechanosensitive osteocytes. In these simulations, a piece of bone tissue was modeled with finite elements to determine local mechanical quantities. The specimen was loaded at the boundaries, and the mechanical adaptation process was simulated until a balance between loading and bone morphology was reached. The assumed process could explain the genesis and adaptation of trabecular patterns. These patterns resembled typical trabecular architectures, including plates and struts,[43]which aligned with the external load orientations.[26]This model demonstrated that the hypothesis of bone remodeling as a locally regulated process, governed by mechanical signals, sensed by osteocytes, is feasible.

In this study, the question is addressed whether temporary alterations in mechanical loads or deficiencies in the metabolic response to mechanical loads could be responsible for the deterioration of bone architecture. Several investigators have proposed that osteoporosis is associated with alterations in the response of bone cells to mechanical loads9, 10, 14, 36; in other words, a change in the mechanosensitivity (set point) of sensor cells. We tested this hypothesis, using the osteocyte-regulated bone-remodeling theory. In addition, the effects of temporary changes of mechanical loads on trabecular bone architecture were investigated. To permit comparison of the results with phenomena as seen in real trabecular bone, the theory was applied to a three-dimensional finite-element model of a reconstructed trabecular bone specimen from a vertebral body. Within the computer simulation model, the mechanical set point of the osteocytes and mechanical loads were varied, and their effects on the trabecular architecture evaluated.

Section snippets

Materials

A core of trabecular bone was excised from the fourth lumbar vertebra of a 37-year-old male autopsy patient. The subject had no history of bone disease. The specimen was digitized using a micro-CT scanner[37]with a resolution of 28 μm. The CT image was processed to obtain the trabecular morphology of the specimen.[37]From the total reconstruction, a 3.9 mm³ specimen was selected for use in the model. The axes of the cube were oriented along the anatomical axes. The digital reconstruction was

Results

During simulations the remodeling process maintained a trabecular architecture. The relative apparent density and apparent stiffness values (in the orthotropic main directions) for all architectures are given in Table 1. The initial morphology adapted to the applied loads by increasing the overall density (Table 1), after which a balance between the loads and the relative apparent density was obtained. This was accomplished by thickening of the existing trabeculae and by the formation of thin

Discussion

We have tested the hypothesis that osteoporosis is caused by a shift in the mechanical set point of osteocytes, which we assumed to be the mechanosensors. In addition, we have looked at the effects of changed loading conditions on the trabecular architecture. For this purpose, a regulatory process was studied, using a computer simulation model in which the architecture is controlled by mechanical load only. Although it is still unclear how bone cells sense mechanical signals, the hypothesis

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Original ArticlesEffect of Mechanical Set Point of Bone Cells on Mechanical Control of Trabecular Bone Architecture

Abstract

Introduction

Section snippets

Materials

Results

Discussion

Bone

Bone

J Biomech

Bone

Bone

Bone Miner

J Biomech

Bone

Bone

J Biomech

J Biomech

Bone

Stimulation of signal transduction pathways in osteoblasts by mechanical strain potentiated by parathyroid hormone

J Bone Miner Res

Estrogen enhances the stimulation of bone collagen synthesis by loading and exogenous prostacyclin, but not prostaglandin E2, in organ cultures of rat ulnae

J Bone Miner Res

Oestrogen amplifies bone’s osteogenic responses to load-bearing in female rat ulna in vitro

Calcif Tissue Int

Candidates for the mechanosensory system in bone

J Biomech Eng

The Laws of Bone Structure

The mechanostatA proposed pathogenetic mechanism of osteoporosis and the bone mass effects of mechanical and nonmechanical agents

Bone

The role of changes in mechanical usage set points in the pathogenesis of osteoporosis

J Bone Miner Res

Simulation of self-organization and functional adaptation in bone

Effects of immobilization, three forms of remobilization, and subsequent deconditioning on bone mineral content and density in rat femora

J Bone Miner Res

A paradigm for skeletal strength homeostasis

J Bone Miner Res

The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures

Calcif Tissue Int

Original Articles
Effect of Mechanical Set Point of Bone Cells on Mechanical Control of Trabecular Bone Architecture