Summary:It is currently believed that the trabecular structure in bone is the result of a dynamic remodeling process controlled bÿ mechanical loads. We propose a regulatory mechanism based on the hypothesis that osteocytes located within the bone sense mechanical signals and that these cells mediate osteoclasts and osteoblasts in their vicinity to adapt bone mass. A computer-simulation model based on these assumptions was used to investigate if the adaptation of bone, in the sense of Wolffs law, and remodeling phenomena, as observed in reality, can be explained by such a local control process. The model produced structures resem bling actual trabecular architectures. The architecture transformed after the external loads were changed, aligning the trabeculae with the actual principal stress orientation, in accordance with Wolffs trajectorial hypothesis. As in reality, the relative apparent density of the structure depended on the magnitude of the applied stresses. Osteocyte density influenced the remodeling rate, which also is consistent with experimental findings. Furthermore, the results indicated that the domain of influence of the osteocytes affects the refine ment of the structure as represented by separation and thickness of the struts. We concluded that the trabec ular adaptation to mechanical load, as described by Wolff, can be explained by a relatively simple regulatory model. The model is useful for investigating the effects of physiological parameters on the development, maintenance, and adaptation of bone.

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Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the load profile and whether different components, such as fluid shear, tension or compression, can influence cells in differing ways. During dynamic loading of intact bone, fluid is pressed through the osteocyte canaliculi, and it has been demonstrated that fluid shear stress stimulates osteocytes to produce signalling molecules. It is less clear how mechanical loads act on mature osteoblasts present on the surface of cancellous or trabecular bone. Although tissue strain and fluid shear stress both cause cell deformation, these stimuli could excite different signalling pathways. This is confirmed by our experimental findings, in human bone cells, that strain applied through the substrate and fluid flow stimulate the release of signalling molecules to varying extents. Nitric oxide and prostaglandin E2 values increased by between two- and nine-fold after treatment with pulsating fluid flow (0.6 +/- 0.3 Pa). Cyclic strain (1000 microstrain) stimulated the release of nitric oxide two-fold, but had no effect on prostaglandin E2. Furthermore, substrate strains enhanced the bone matrix protein collagen I two-fold, whereas fluid shear caused a 50% reduction in collagen I. The relevance of these variations is discussed in relation to bone growth and remodelling. In applications such as tissue engineering, both stimuli offer possibilities for enhancing bone cell growth in vitro.

Recently, it was suggested that osteocytes are involved in the regulation of bone remodeling. We have examined human trabecular bone of the iliac crest of fracture patients and control subjects to determine if osteoporosis is associated with changes in osteocyte density or osteocyte death. The relationships of these parameters with age was also investigated. It was found that osteocyte death was not related to age, nor was it increased in osteoporosis compared with the controls. In healthy adults ranging from 30 to 91 years, lacunar number per bone area decreases with advancing age, from about 210/mm 2 to 150/mm 2. Significantly higher lacunar and osteocyte numbers per bone tissue volume were found in osteoporotics than in controls (17,100 lacunae/mm 3 and 13,300 osteocytes/mm 3 vs. 12,900 lacunae/mm 3 and 10,500 osteocytes/mm 3, respectively), whereas lacunar area was significantly reduced in osteoporotics (from 44.1 ~tm 3 to 39.1 lam2). These findings are compatible with the hypothesis that, in osteoporosis, osteoblasts produce less bone per cell. This can in turn explain the reduced wall thickness, which has previously been described as characteristic for osteoporosis. (Bone 18:109-113; 1996)