Altered lacunar and vascular porosity in osteogenesis imperfecta mouse bone as revealed by synchrotron tomography contributes to bone fragility
Osteogenesis imperfecta (brittle bone disease) is caused by mutations in the collagen genes and results in skeletal fragility. Changes in bone porosity at the tissue level indicate changes in bone metabolism and alter bone mechanical integrity. We investigated the cortical bone tissue porosity of a mouse model of the disease, oim, in comparison to a wild type (WT-C57BL/6), and examined the influence of canal architecture on bone mechanical performance. High-resolution 3D representations of the posterior tibial and the lateral humeral mid-diaphysis of the bones were acquired for both mouse groups using synchrotron radiation-based computed tomography at a nominal resolution of 700nm. Volumetric morphometric indices were determined for cortical bone, canal network and osteocyte lacunae. The influence of canal porosity architecture on bone mechanics was investigated using microarchitectural finite element (μFE) models of the cortical bone. Bright-field microscopy of stained sections was used to determine if canals were vascular. Although total cortical porosity was comparable between oim and WT bone, oim bone had more numerous and more branched canals (p<0.001), and more osteocyte lacunae per unit volume compared to WT (p<0.001). Lacunae in oim were more spherical in shape compared to the ellipsoidal WT lacunae (p<0.001). Histology revealed blood vessels in all WT and oim canals. μFE models of cortical bone revealed that small and branched canals, typical of oim bone, increase the risk of bone failure. These results portray a state of compromised bone quality in oim bone at the tissue level, which contributes to its deficient mechanical properties.
Source Read the full article
Shaping our bones
We know that applying a force to a bone during its development can influence its growth and shape. In ancient China parents bound girls’ feet to prevent growth, as small “lotus sized” feet were considered beautiful. In a few African and Asian cultures an elongated neck is considered a sign of beauty. Women of the Kayan people (Burma, Myanmar) begin to wear neck coils from as young as two and continue to add successive brass coils as they grow (see figure 1). The effect of this technique is an elongated neck, but vertebrae do not actually elongate. The weight of the coils instead applies enough pressure on the shoulder blades to eventually deform them, generating the illusion of a long neck.
But can we use our understanding of how developing bone reacts to mechanical forces to help people suffering from diseases that lead to bone deformities? Researchers have investigated this question for years. They have developed mathematical models to help predict the shape of our bones. Using these models it is now possible to predict, for example, how the femur of a child will grow over the next few months by analysing the child’s walking patterns. The mathematical models of bone growth will eventually make it possible to prevent bone deformities in children with diseases such as cerebral palsy and hip dysplasia.
Influence of altered gait patterns on the hip joint contact forces
Children who exhibit gait deviations often present a range of bone deformities, particularly at the proximal femur. Altered gait may affect bone growth and lead to deformities by exerting abnormal stresses on the developing bones. The objective of this study was to calculate variations in the hip joint contact forces with different gait patterns. Muscle and hip joint contact forces of four children with different walking characteristics were calculated using an inverse dynamic analysis and a static optimisation algorithm. Kinematic and kinetic analyses were based on a generic musculoskeletal model scaled down to accommodate the dimensions of each child. Results showed that for all the children with altered gaits both the orientation and magnitude of the hip joint contact force deviated from normal. The child with the most severe gait deviations had hip joint contact forces 30% greater than normal, most likely due to the increase in muscle forces required to sustain his crouched stance. Determining how altered gait affects joint loading may help in planning treatment strategies to preserve correct loading on the bone from a young age.
Mechanobiological prediction of proximal femoral deformities in children with cerebral palsy
Children with cerebral palsy (CP) walk with altered gait and frequently exhibit proximal femoral deformities, such as anteversion and coxa valga. The objective of this research was to investigate the effect of specific gait patterns on the femoral morphology in CP.
In this study, the mechanobiological principles were implemented on a three-dimensional finite element (FE) model of the proximal femur in order to predict changes in morphology over time in the healthy and in CP children. This model relies on the assumption that cyclic octahedral shear stress promotes growth and cyclic hydrostatic compressive stress inhibits growth. Growth was simulated over 16 iterations, representing approximately five months of growth.
The FE model predicts an increase in the femoral anteversion and coxa-valga for CP loading conditions when compared with healthy ones. Understanding the role of loading in skeletal morphogenesis may help prevent bone deformities and improve function in children with gait abnormalities.
Correlation Between Lower Limb Bone Morphology and Gait Characteristics in Children With Spastic Diplegic Cerebral Palsy
Children with spastic diplegic cerebral palsy (CP) exhibit abnormal walking patterns and frequently develop lower limb, long bone deformities. It is important to determine if any relationship exists between bone morphology and movement of the lower limbs in children with CP. This is necessary to explain and possibly prevent the development of these deformities.
This study investigated the relationship between bone morphology and gait characteristics in ten healthy children (age range: 6-13 years; mean 8 years and 7 months, SD +/- 2 years and 7 months) and nine children with spastic diplegic CP (age range: 6-12 years; mean 9 years and 2.5 months, SD +/- 1 year and 10.5 months) with no previous surgery. Three-dimensional magnetic resonance images were analysed to define bone morphology. Morphological characteristics, such as the bicondylar angle, neck-shaft angle, anteversion angle and tibial torsion, were measured. Gait analyses were performed to obtain kinematic characteristics of CP and normal children’s gait. Principal component analysis was used to reduce the dimensionality of 27 parameters (26 kinematics variables and age of the children) to eight independent variables. Correlations between gait and bone morphology were determined for both groups of children.
Results indicated that in healthy children, hip adduction was correlated with neck-shaft and bicondylar angles. In CP children, pelvic obliquity correlated with neck-shaft angle, and foot rotation with bicondylar angle. In the transverse plane, hip and pelvic rotational kinematics were related to femoral anteversion in healthy children and to tibial torsion in CP children.
Different development was observed in femoral and tibial morphology between CP and healthy children. The relationship between bone shape and dynamic gait patterns also varied between these populations. This needs to be taken into account, particularly when surgical treatment is planned.
Understanding the relationship between gait abnormality and bone deformity could eventually help in developing treatment regimes that will address gait deviations at the correct level and promote normal bone growth in children with CP.
Determination of gait patterns in children with spastic diplegic cerebral palsy using principal components
This study developed an objective graphical classification method of spastic diplegic cerebral palsy (CP) gait patterns based on principal component analysis (PCA). Gait analyses of 20 healthy and 20 spastic diplegic CP children were examined to define gait characteristics. PCA was used to reduce the dimensionality of 27 parameters (26 selected kinematics variables and age of the children) for the 40 subjects in order to identify the dominant variability in the data. Fuzzy C-means cluster analysis was performed plotting the first three principal components, which accounted for 61% of the total variability. Results indicated that only the healthy children formed a distinct cluster; however it was possible to recognise gait patterns in overlapping clusters in children with spastic diplegia. This study demonstrates that it is possible to quantitatively classify gait types in CP using PCA. Graphical classification of gait types could assist in clinical evaluation of the children and serve as a validation of clinical reports as well as aid treatment planning.