Is spinal neuromuscular function asymmetrical in adolescents with idiopathic scoliosis compared to those without scoliosis?: A narrative review of surface EMG studies.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity occurring between ages of 10-18 years. We aimed to present a reasoned synthesis of the published evidence for and against asymmetrical paraspinal muscle activation in AIS. PubMed and Embase databases were searched using terms: adolescent idiopathic scoliosis AND electromyogra* (EMG). Identified studies (n = 94) were screened for eligibility. We identified 16 studies, from which 136 EMG outcome measures contributed to the review. For EMG onset, one of two studies provided evidence of earlier muscle activation on the convex compared to concave side of the spine, particularly in those with progressive AIS. For EMG amplitude, 43 outcome measures provided evidence of convex > concave activation, 85 outcomes supported no difference between sides, and 8 outcomes supported concave > convex activation. Greater activity on the convex than concave side was more commonly demonstrated at the scoliosis curve apex level, in people with single right thoracic [progressive] curves, during postural tasks. Further research is needed to determine the relationships between muscle activity asymmetry and spinal curve parameters in a variety of motor tasks. Recommendations are provided to improve methodological quality for future studies of spinal neuromuscular function in AIS, as well as more comprehensive and transparent reporting of methods and results.

The Application of Pulsed Electromagnetic Fields (PEMFs) for Bone Fracture Repair: Past and Perspective Findings.

Bone fractures are one of the most commonly occurring injuries of the musculoskeletal system. A highly complex physiological process, fracture healing has been studied extensively. Data from in vivo, in vitro and clinical studies, have shown pulsed electromagnetic fields (PEMFs) to be highly influential in the fracture repair process. Whilst the underlying mechanisms acting to either inhibit or advance the physiological processes are yet to be defined conclusively, several non-invasive point of use devices have been developed for the clinical treatment of fractures. With the complexity of the repair process, involving many components acting at different time steps, it has been a challenge to determine which PEMF exposure parameters (i.e., frequency of field, intensity of field and dose) will produce the most optimal repair. In addition, the development of an evidence-backed device comes with challenges of its own, with many elements (including process of exposure, construct materials and tissue densities) being highly influential to the field exposed. The objective of this review is to provide a broad recount of the applications of PEMFs in bone fracture repair and to then demonstrate what is further required for enhanced therapeutic outcomes.

Lacunar-canalicular network in femoral cortical bone is reduced in aged women and is predominantly due to a loss of canalicular porosity.

The lacunar-canalicular network (LCN) of bone contains osteocytes and their dendritic extensions, which allow for intercellular communication, and are believed to serve as the mechanosensors that coordinate the processes of bone modeling and remodeling. Imbalances in remodeling, for example, are linked to bone disease, including fragility associated with aging. We have reported that there is a reduction in scale for one component of the LCN, osteocyte lacunar volume, across the human lifespan in females. In the present study, we explore the hypothesis that canalicular porosity also declines with age. To visualize the LCN and to determine how its components are altered with aging, we examined samples from young (age: 20-23 y; n = 5) and aged (age: 70-86 y; n = 6) healthy women donors utilizing a fluorescent labelling technique in combination with confocal laser scanning microscopy. A large cross-sectional area of cortical bone spanning the endosteal to periosteal surfaces from the anterior proximal femoral shaft was examined in order to account for potential trans-cortical variation in the LCN. Overall, we found that LCN areal fraction was reduced by 40.6% in the samples from aged women. This reduction was due, in part, to a reduction in lacunar density (21.4% decline in lacunae number per given area of bone), but much more so due to a 44.6% decline in canalicular areal fraction. While the areal fraction of larger vascular canals was higher in endosteal vs. periosteal regions for both age groups, no regional differences were observed in the areal fractions of the LCN and its components for either age group. Our data indicate that the LCN is diminished in aged women, and is largely due to a decline in the canalicular areal fraction, and that, unlike vascular canal porosity, this diminished LCN is uniform across the cortex.

Estimation of anisotropic permeability in trabecular bone based on microCT imaging and pore-scale fluid dynamics simulations.

In this paper, a comprehensive framework is proposed to estimate the anisotropic permeability matrix in trabecular bone specimens based on micro-computed tomography (microCT) imaging combined with pore-scale fluid dynamics simulations. Two essential steps in the proposed methodology are the selection of (i) a representative volume element (RVE) for calculation of trabecular bone permeability and (ii) a converged mesh for accurate calculation of pore fluid flow properties. Accurate estimates of trabecular bone porosities are obtained using a microCT image resolution of approximately 10 µm. We show that a trabecular bone RVE in the order of 2 × 2 × 2 mm3 is most suitable. Mesh convergence studies show that accurate fluid flow properties are obtained for a mesh size above 125,000 elements. Volume averaging of the pore-scale fluid flow properties allows calculation of the apparent permeability matrix of trabecular bone specimens. For the four specimens chosen, our numerical results show that the so obtained permeability coefficients are in excellent agreement with previously reported experimental data for both human and bovine trabecular bone samples. We also identified that bone samples taken from long bones generally exhibit a larger permeability in the longitudinal direction. The fact that all coefficients of the permeability matrix were different from zero indicates that bone samples are generally not harvested in the principal flow directions. The full permeability matrix was diagonalized by calculating the eigenvalues, while the eigenvectors showed how strongly the bone sample's orientations deviated from the principal flow directions. Porosity values of the four bone specimens range from 0.83 to 0.86, with a low standard deviation of ± 0.016, principal permeability values range from 0.22 to 1.45 ⋅ 10 -8 m2, with a high standard deviation of ± 0.33. Also, the anisotropic ratio ranged from 0.27 to 0.83, with high standard deviation. These results indicate that while the four specimens are quite similar in terms of average porosity, large variability exists with respect to permeability and specimen anisotropy. The utilized computational approach compares well with semi-analytical models based on homogenization theory. This methodology can be applied in bone tissue engineering applications for generating accurate pore morphologies of bone replacement materials and to consistently select similar bone specimens in bone bioreactor studies.

A multiscale mechanobiological model of bone remodelling predicts site-specific bone loss in the femur during osteoporosis and mechanical disuse.

We propose a multiscale mechanobiological model of bone remodelling to investigate the site-specific evolution of bone volume fraction across the midshaft of a femur. The model includes hormonal regulation and biochemical coupling of bone cell populations, the influence of the microstructure on bone turnover rate, and mechanical adaptation of the tissue. Both microscopic and tissue-scale stress/strain states of the tissue are calculated from macroscopic loads by a combination of beam theory and micromechanical homogenisation. This model is applied to simulate the spatio-temporal evolution of a human midshaft femur scan subjected to two deregulating circumstances: (i) osteoporosis and (ii) mechanical disuse. Both simulated deregulations led to endocortical bone loss, cortical wall thinning and expansion of the medullary cavity, in accordance with experimental findings. Our model suggests that these observations are attributable to a large extent to the influence of the microstructure on bone turnover rate. Mechanical adaptation is found to help preserve intracortical bone matrix near the periosteum. Moreover, it leads to non-uniform cortical wall thickness due to the asymmetry of macroscopic loads introduced by the bending moment. The effect of mechanical adaptation near the endosteum can be greatly affected by whether the mechanical stimulus includes stress concentration effects or not.

The relationship between porosity and specific surface in human cortical bone is subject specific.

A characteristic relationship for bone between bone volume fraction (BV/TV) and specific surface (BS/TV) has previously been proposed based on 2D histological measurements. This relationship has been suggested to be bone intrinsic, i.e., to not depend on bone type, bone site and health state. In these studies, only limited data comes from cortical bone. The aim of this paper was to investigate the relationship between BV/TV and BS/TV in human cortical bone using high-resolution micro-CT imaging and the correlations with subject-specific biometric data such as height, weight, age and sex. Images from femoral cortical bone samples of the Melbourne Femur Collection were obtained using synchrotron radiation micro-CT (SPring8, Japan). Sixteen bone samples from thirteen individuals were analysed in order to find bone volume fraction values ranging from 0.20 to 1. Finally, morphological models of the tissue microstructure were developed to help explain the relationship between BV/TV and BS/TV. Our experimental findings indicate that the BV/TV vs BS/TV relationship is subject specific rather than intrinsic. Sex and pore density were statistically correlated with the individual curves. However no correlation was found with body height, weight or age. Experimental cortical data points deviate from interpolating curves previously proposed in the literature. However, these curves are largely based on data points from trabecular bone samples. This finding challenges the universality of the curve: highly porous cortical bone is significantly different to trabecular bone of the same porosity. Finally, our morphological models suggest that changes in BV/TV within the same sample can be explained by an increase in pore area rather than in pore density. This is consistent with the proposed mechanisms of age-related endocortical bone loss. In addition, these morphological models highlight that the relationship between BV/TV and BS/TV is not linear at high BV/TV as suggested in the literature but is closer to a square root function.

Mathematical modeling of postmenopausal osteoporosis and its treatment by the anti-catabolic drug denosumab.

Denosumab, a fully human monoclonal antibody, has been approved for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab rests on its ability to inhibit osteoclast differentiation. Here, we present a computational approach on the basis of coupling a pharmacokinetics model of denosumab with a pharmacodynamics model for quantifying the effect of denosumab on bone remodeling. The pharmacodynamics model comprises an integrated systems biology-continuum micromechanics approach, including a bone cell population model, considering the governing biochemical factors of bone remodeling (including the action of denosumab), and a multiscale micromechanics-based bone mechanics model, for implementing the mechanobiology of bone remodeling in our model. Numerical studies of postmenopausal osteoporosis show that denosumab suppresses osteoclast differentiation, thus strongly curtailing bone resorption. Simulation results also suggest that denosumab may trigger a short-term bone volume gain, which is, however, followed by constant or decreasing bone volume. This evolution is accompanied by a dramatic decrease of the bone turnover rate by more than one order of magnitude. The latter proposes dominant occurrence of secondary mineralization (which is not anymore impeded through cellular activity), leading to higher mineral concentration per bone volume. This explains the overall higher bone mineral density observed in denosumab-related clinical studies.

Spatio-temporal structure of cell distribution in cortical bone multicellular units: a mathematical model.

Bone remodelling maintains the functionality of skeletal tissue by locally coordinating bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts) in the form of Bone Multicellular Units (BMUs). Understanding the emergence of such structured units out of the complex network of biochemical interactions between bone cells is essential to extend our fundamental knowledge of normal bone physiology and its disorders. To this end, we propose a spatio-temporal continuum model that integrates some of the most important interaction pathways currently known to exist between cells of the osteoblastic and osteoclastic lineage. This mathematical model allows us to test the significance and completeness of these pathways based on their ability to reproduce the spatio-temporal dynamics of individual BMUs. We show that under suitable conditions, the experimentally observed structured cell distribution of cortical BMUs is retrieved. The proposed model admits travelling-wave-like solutions for the cell densities with tightly organised profiles, corresponding to the progression of a single remodelling BMU. The shapes of these spatial profiles within the travelling structure can be linked to the intrinsic parameters of the model such as differentiation and apoptosis rates for bone cells. In addition to the cell distribution, the spatial distribution of regulatory factors can also be calculated. This provides new insights on how different regulatory factors exert their action on bone cells leading to cellular spatial and temporal segregation, and functional coordination.

Effects of 6-MBOA on reproductive function in ponies, mice, rats and mink.

The effect on reproduction of the plant derivative 6-methoxybenzoxazolinone (6-MBOA), which stimulates reproductive function in voles, was tested in pony mares, laboratory mice and rats, and mink. There was not a significant effect of intravenous injections of 6-MBOA on the ovarian follicles during the transition between the anovulatory and ovulatory seasons in mares. No significant effect of intraperitoneal injections of 6-MBOA on the weight of uterus or ovaries was found in eight-week-old mice, failing to confirm the results of an earlier report. In immature white rats, 6-MBOA treatment resulted in an increase in uterine weight (P<0.05) at the lowest dose tested (0.03 mug/rat; mean for controls, 34 +/-2 mg; treated, 47 +/-5 mg). However, no significant effect was found on the weights of the ovaries and other glands or in coded scores for ovarian stimulation and uterine fluid distention. Adding 1.5 mg 6-MBOA to the daily feed ration of mink beginning two weeks before the mating season did not affect the mean number of kits born. Nulliparous female mink had smaller (P<0.001) litter size than multiparous females. In addition, of the mink that whelped, there were more (P<0.01) nulliparous females (25 118 ) than multiparous females (9 144 ) that lost one or more kits within 48 hours. These results, however, were not altered by 6-MBOA treatment.