Using Finite Element Modeling in Bone Mechanoadaptation.

PURPOSE OF THE REVIEW: Bone adapts structure and material properties in response to its mechanical environment, a process called mechanoadpatation. For the past 50 years, finite element modeling has been used to investigate the relationships between bone geometry, material properties, and mechanical loading conditions. This review examines how we use finite element modeling in the context of bone mechanoadpatation. RECENT FINDINGS: Finite element models estimate complex mechanical stimuli at the tissue and cellular levels, help explain experimental results, and inform the design of loading protocols and prosthetics. FE modeling is a powerful tool to study bone adaptation as it complements experimental approaches. Before using FE models, researchers should determine whether simulation results will provide complementary information to experimental or clinical observations and should establish the level of complexity required. As imaging technics and computational capacity continue increasing, we expect FE models to help in designing treatments of bone pathologies that take advantage of mechanoadaptation of bone.

Manipulating load-induced fluid flow in vivo to promote bone adaptation.

Mechanical stimulation is critical to maintaining bone mass and strength. Strain has been commonly thought of as the mechanical stimulus driving bone adaptation. However, numerous studies have hypothesized that fluid flow in the lacunar-canalicular system plays a role in mechanoadaptation. The role of fluid flow compared to strain magnitude on bone remodeling has yet to be characterized. This study aimed to determine the contribution of fluid flow velocity compared to strain on bone adaptation. We used finite element modeling to design in vivo experiments, manipulating strain and fluid flow contributions. Using a uniaxial compression tibia model in mice, we demonstrated that high fluid flow velocity results in significant bone adaptation even under low strain magnitude. In contrast, high strain magnitude paired with low fluid velocity does not trigger a bone response. These findings support previous hypotheses stating that fluid flow is the principal mechanical stimulus driving bone adaptation. Moreover, they give new insights regarding bone adaptative response and provide new pathways toward treatment against age-related mechanosensitivity loss in bone.

Mechanoadaptation of the bones of mice with high fat diet induced obesity in response to cyclical loading.

An upward trend in childhood obesity implies a great need to determine its effects, both immediate and long-term. Obesity is osteoprotective in adults, but we know very little about the effects of obesity on the growing skeleton, particularly its ability to adapt to load. The objective of this research is to assess bone mechanoadaptation in adolescent obese mice. Ten mice were fed a high-fat diet (HFD) from 4 to 16 weeks of age, while a control group of the same size received a normal diet (ND). At 14 weeks of age, right tibiae were cyclically loaded with a 12 N peak load for HFD mice and a 9 N peak load for ND mice three times a week for two weeks, resulting in equal peak strains of about 2500 microstrain. At 16 weeks of age, mice were sacrificed, and tibiae and gonadal fat pads were dissected. Fat pads were weighed as an obesity indicator, and tibiae were imaged with microCT to measure bone structure. The left tibiae (nonloaded) were subsequently decalcified, stained with osmium, and scanned to quantify marrow fat. Results showed that HFD mice had larger tibial cross-sectional areas compared to ND mice, as well as greater marrow adiposity. However, there was no significant difference in the amount of bone adaptation in the cortical or trabecular bone between the two groups. This indicates that the bones of HFD and ND mice adapt equally well to loading.

Measuring 3D growth plate shape: Methodology and application to cam morphology.

Physeal changes corresponding to cam morphology are currently measured using two-dimensional (2D) methods. These methods are limited by definitions of the femoral neck axis and head center that are dependent on the radiographic plane of view. To address these limitations, we developed three-dimensional (3D) methods for analyzing continuous growth plate shape using magnetic resonance imaging scans. These new methods rely on a single definition of the femoral neck axis and head center that are both nondependent on the radiographic plane of view and allow for analysis of growth plate shape across the growth plate surface (performed using statistical parametric mapping). Using our 3D method, we analyzed the position of the growth plate in the femoral head (relative to a plane tangent to the femoral head) and the curvature of the growth plate (relative to a plane through the center of the growth plate) in 9-16-year-old males at risk for cam morphology and their recreationally active peers (n = 17/cohort). These two measurements provide an avenue to separately analyze the effects of these variables in the overall growth plate shape. We detected differences in growth plate shape with age in recreationally active adolescents but did not detect differences between at risk and recreationally adolescents.

Increased Cellular Presence After Sciatic Neurectomy Improves the Bone Mechano-adaptive Response in Aged Mice.

The mechano-adaptive response of bone to loading in the murine uniaxial tibial loading model is impaired in aged animals. Previous studies have shown that in aged mice, the amount of bone formed in response to loading is augmented when loads are applied following sciatic neurectomy. The synergistic effect of neurectomy and loading remains to be elucidated. We hypothesize that sciatic neurectomy increases cellular presence, thereby augmenting the response to load in aged mice. We examined bone adaptation in four groups of female C57BL/6J mice, 20-22 months old: (1) sham surgery + 9N loading; (2) sciatic neurectomy, sacrificed after 5 days; (3) sciatic neurectomy, sacrificed after 19 days; (4) sciatic neurectomy + 9N loading. We examined changes in bone cross sectional properties with micro-CT images, and static and dynamic histomorphometry with histological sections taken at the midpoint between tibiofibular junctions. The response to loading at 9N was not detectable with quantitative micro-CT data, but surface-specific histomorphometry captured an increase in bone formation in specific regions. 5 days following sciatic neurectomy, the amount of bone in the neurectomized leg was the same as the contralateral leg, but 19 days following sciatic neurectomy, there was significant bone loss in the neurectomized leg, and both osteoclasts and osteoblasts were recruited to the endosteal surfaces. When sciatic neurectomy and loading at 9N were combined, 3 out of 4 bone quadrants had increased bone formation, on the endosteal and periosteal surfaces (increased osteoid surface and mineralizing surface respectively). These data demonstrate that sciatic neurectomy increases cellular presence on the endosteal surface. With long-term sciatic-neurectomy, both osteoclasts and osteoblasts were recruited to the endosteal surface, which resulted in increased bone formation when combined with a sufficient mechanical stimulus. Controlled and localized recruitment of both osteoblasts and osteoclasts combined with appropriate mechanical loading could inform therapies for mechanically-directed bone formation.