Capturing microscopic features of bone remodeling into a macroscopic model based on biological rationales of bone adaptation

Abstract

To understand Wolff's law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account. The proposed models were categorized into two groups according to whether the remodeling equilibrium state was defined globally or locally, i.e., the global or local uniformity models. Each remodeling stimulus in the proposed models was quantitatively evaluated through image-based finite element analyses of a swine cancellous bone, according to two introduced criteria associated with the trabecular volume and orientation at remodeling equilibrium based on biological rationales. The evaluation suggested that nonuniformity of the mean stress gradient in the local uniformity model, one of the proposed stimuli, has high validity. Furthermore, the adaptive potential of each stimulus was discussed based on spatial distribution of a remodeling stimulus on the trabecular surface. The theoretical consideration of a remodeling stimulus based on biological rationales of bone adaptation would contribute to the establishment of a clinically applicable and reliable simulation model of bone remodeling.

Aging effects on osteoclast progenitor dynamics affect variability in bone turnover via feedback regulation

“… 45-47 In silico studies of bone metabolism have described a pathological process in which the breakdown of this feedback system due to an abnormal bone turnover balance leads to significant bone loss. 17 , 24 , 48-51 In this study, we further demonstrated that the feedback system associated with the consumptive loss of progenitors is another homeostatic mechanism that prevents rapid bone loss owing to abnormal bone turnover. Thus, our model enables a comprehensive understanding of bone metabolism, simultaneously based on the interaction across the lineage (i.e., between osteoclasts and osteoblasts) and the interaction within the lineage (i.e., between upstream progenitors and downstream differentiated cells).…”

“…An FE model of the cancellous bone was constructed from X-ray micro-CT images of a swine femoral head based on a previous procedure reported by Kim et al. 24 The model was constructed as a cube of 45 × 45 × 45 voxels, and each element was a cubic voxel with an edge size of 24 μm. The bone was assumed to be a homogeneous and isotropic linear elastic material with a Young’s modulus E = 20 GPa and a Poisson’s ratio ν = 0.3.…”

In silico experiments of bone remodeling explore metabolic diseases and their drug treatment

“…In addition, this model is based on the hypothesis that osteocytes regulate bone resorption and formation to achieve a locally uniform stress/strain state via bone remodeling (18,19), which means that bone remodeling is susceptible to the local spatial variation of stress/strain in the bone tissue rather than their magnitude. Considering that osteocytes in the bone matrix are believed to be stimulated by interstitial fluid flow (20), which is driven by the gradient of fluid pressure instead of the fluid pressure itself, this hypothesis would be reasonable and is validated through a theoretical study (21).…”

2D geometric model of the human femoral neck in frontal projection

“…Шейка бедренной кости имеет неправильную форму и расширяется как при переходе в головку, так и в вертельную область. Для характеристики геометрии шейки с проксимальной и с дистальной сторон выполняли построение двух линий, параллельных ее оси (16,17), каждая из которых накладывалась на верхнюю и нижнюю поверхности в наиболее узком месте (рис. 1, ж).…”

“…Костная ткань представляет собой опорную ткань организма и характеризуется помимо прочего способностью к постоянному обновлению внеклеточного матрикса (ремоделированию). Это возможно за счет тесного взаимодействия остеобластов, остеоцитов и остеокластов, которые обеспечивают постоянное обновление костной ткани [1,16,20]. Данный процесс направлен на адаптивную перестройку структуры костей в условиях изменения физической нагрузки, определяя реакцию скелета на деформации.…”