Muscle volume is related to trabecular and cortical bone architecture in typically developing children

Introduction: Muscle is strongly related to cortical bone architecture in children; however, the relationship between muscle volume and trabecular bone architecture is poorly studied. The aim of this study was to determine if muscle volume is related to trabecular bone architecture in children and if the relationship is different than the relationship between muscle volume and cortical bone architecture. Materials and methods: Forty typically developing children (20 boys and 20 girls; 6 to 12. y) were included in the study. Measures of trabecular bone architecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the distal femur, cortical bone architecture [cortical volume, total volume, section modulus (Z) and polar moment of inertia (J)] in the midfemur, muscle volume in the midthigh and femur length were assessed using magnetic resonance imaging. Total physical activity and moderate-to-vigorous physical activity were assessed using an accelerometer-based activity monitor worn around the waist for four days. Calcium intake was assessed using diet records. Relationships among the measures were tested using multiple linear regression analysis. Results: Muscle volume was moderately-to-strongly related to measures of trabecular bone architecture [appBV/TV (r=0.81), appTb.N (r=0.53), appTb.Th (r=0.67), appTb.Sp (r=-0.71); all p0.05). Because muscle volume and femur length were strongly related (r=0.91, p2.77). When muscle volume/femur length2.77 was included in a regression model with femur length, sex, physical activity and calcium intake, muscle volume/femur length2.77 was a significant predictor of appBV/TV, appTb.Th and appTb.Sp (partial r=0.44 to 0.49, p<0.05) and all measures of cortical bone architecture (partial r=0.47 to 0.54; p<0.01). Conclusions: The findings suggest that muscle volume in the midthigh is related to trabecular bone architecture in the distal femur of typically developing children. The relationship is weaker than the relationship between muscle volume in the midthigh and cortical bone architecture in the midfemur, but the discrepancy is driven, in large part, by the greater dependence of cortical bone architecture measures on femur length

Peripheral quantitative computed tomography (pQCT) for the assessment of bone strength in most of bone affecting conditions in developmental age: a review.

Peripheral quantitative computed tomography provides an automatical scan analysis of trabecular and cortical bone compartments, calculating not only their bone mineral density (BMD), but also bone geometrical parameters, such as marrow and cortical Cross-Sectional Area (CSA), Cortical Thickness (CoTh), both periosteal and endosteal circumference, as well as biomechanical parameters like Cross-Sectional Moment of Inertia (CSMI), a measure of bending, polar moment of inertia, indicating bone strength in torsion, and Strength Strain Index (SSI). Also CSA of muscle and fat can be extracted. Muscles, which are thought to stimulate bones to adapt their geometry and mineral content, are determinant to preserve or increase bone strength; thus, pQCT provides an evaluation of the functional ‘muscle-bone unit’, defined as BMC/muscle CSA ratio. This functional approach to bone densitometry can establish if bone strength is normally adapted to the muscle force, and if muscle force is adequate for body size, providing more detailed insights to targeted strategies for the prevention and treatment of bone fragility. The present paper offers an extensive review of technical features of pQCT and its possible clinical application in the diagnostic of bone status as well as in the monitoring of the skeleton’s health follow-up

The developing juvenile talus:Radiographic identification of distinct ontogenetic phases and structural trajectories

Trabecular bone architecture in the developing skeleton is a widely researched area of bone biomechanics; however, despite its significance in weight-bearing locomotion, the developing talus has received limited examination. This study investigates the talus with the purpose of identifying ontogenetic phases and developmental patterns that contribute to the growing understanding of the developing juvenile skeleton. Colour gradient mapping and radiographic absorptiometry were utilised to investigate 62 human tali from 38 individuals, ranging in age-at-death from 28 weeks intrauterine to 20 years of age. The perinatal talus exhibited a rudimentary pattern comparable to the structural organisation observed within the late adolescent talus. This early internal organisation is hypothesised to be related to the vascular pattern of the talus. After 2 years of age, the talus demonstrated refinement, where radiographic trajectories progressively developed into patterns consistent with adult trabecular organisation, which are linked to the forces associated with the bipedal gait, suggesting a strong influence of biomechanical forces on the development of the talus.</p

Characterisation of disuse-related osteoporosis in an animal model of spinal cord injury

Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected.Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected

Treatment of osteoporosis in a mouse model of Duchenne muscular dystrophy using black bear parathyroid hormone

Duchenne muscular dystrophy (DMD) is a progressive disease affecting skeletal and cardiac muscle, as well as bone. Long term disuse and glucocorticoid treatments cause progressive osteoporosis in DMD patients, leading to an increase in fracture incidence. Treatments for osteoporosis in these patients have not been widely explored. Parathyroid hormone (PTH), an anabolic treatment for post-menopausal osteoporosis, could benefit DMD patients by improving skeletal properties and reducing fracture risk. Other PTH analogues are not currently FDA approved to treat osteoporosis, but may have improved osteogenic effects compared to the human analogue. Black bear PTH is especially promising as an osteoporosis treatment for the DMD population. Black bears are unique models of bone maintenance during disuse, since during six months of inactivity (hibernation), they maintain skeletal properties, unlike other hibernators. Additionally, black bear PTH has been correlated to bone formation markers during hibernation, indicating it may be, at least in part, the mechanism by which bears maintain bone during disuse. Employing black bear PTH as a treatment for osteoporosis in DMD patients could greatly improve quality of life for these individuals, and reduce the pain and expense associated with frequent fractures

The effect of exercise and nutrition on the mechanostat

In this review, we discuss the effect of increased and decreased loading and nutrition deficiency on muscle and bone mass and strength (and bone length and architecture) independently and combined. Both exercise and nutrition are integral components of the mechanostat model but both have distinctly different roles. Mechanical strain imparted by muscle action is responsible for the development of the external size and shape of the bone and subsequently the bone strength. In contrast, immobilization during growth results in reduced growth in bone length and a loss of bone strength due to large losses in bone mass (a result of endosteal resorption in cortical bone and trabecular thinning) and changes in geometry (bone shafts do not develop their characteristic shape but rather develop a rounded default shape). The use of surrogate measures for peak muscle forces acting on bone (muscle strength, size, or mass) limits our ability to confirm a cause-and-effect relationship between peak muscle force acting on bone and changes in bone strength. However, the examples presented in this review support the notion that under adequate nutrition, exercise has the potential to increase peak muscle forces acting on bone and thus can lead to a proportional increase in bone strength. In contrast, nutrition alone does not influence muscle or bone in a dose-dependent manner. Muscle and bone are only influenced when there is nutritional deficiency &ndash; and in this case the effect is profound. Similar to immobilization, the immediate effect of malnutrition is a reduction in longitudinal growth. More specifically, protein and energy malnutrition results in massive bone loss due to endosteal resorption in cortical bone and trabecular thinning. Unlike loading however, there is indirect evidence that severe malnutrition when associated with menstrual dysfunction can shift the mechanostat set point upward, thus leading to less bone accrual for a given amount of bone strain.<br /

Exercise and Bone: Older Adults, Type II Diabetes, and Ketogenic Diets

Exercise is a well-appreciated modulator of bone and has other positive implications for overall fitness and health. The purpose of this dissertation was to determine the effects of exercise on bone in conjunction with other known modifiers: old age, type II diabetes mellitus (T2DM), and ketogenic diets. The three studies discussed in this dissertation utilized multiple methods of measuring bone to examine the effect of exercise on bone in individuals with type II diabetes, rodents consuming a ketogenic diet, and older adults participating in a novel resistance training intervention. The first study examined the effects of a 9-month resistance, aerobic, or combination exercise intervention on bone in individuals with T2DM. Whole-body and whole-body derived regional measures of bone mineral density (BMD) were obtained via dual-energy x-ray absorptiometry (DXA) and used to determine the effects. While the entire cohort, control group included, showed significant increases in BMD after a 9-month intervention, the lack of differences between groups, was surprising. An effect of exercise on bone in individuals with T2DM was not revealed by measures of BMD. The second study utilized rodents to determine the effects of a 6-week ketogenic dietary intervention interceded by a 3-week exercise intervention on their trabecular and cortical bone morphology, measured via micro-computed tomography. Our results did not identify any detriments in bone morphology in response to a ketogenic diet alone, but positive changes in trabecular morphology and density induced by exercise in mice fed a control diet were negated by the ketogenic diet. The last study examined the effects of resistance training along with low intensity breaks in sedentary activity on BMD, trabecular bone score (TBS), and serum markers of bone turnover in older adults. Changes in whole-body BMD, lumbar spine BMD, and TBS were not found in response to the 4-month resistance training intervention. Serum markers for bone turnover did not provide any additional context due to reagent, equipment, and technician error. Future re-analysis may be attempted, but for the purpose of this dissertation, the analysis of blood markers for bone turnover was too poor and not included

Exploration of the Effects of Developmental Coordination Disorder on Skeletal Development from Childhood through to Early Adulthood

This thesis examined bone development from childhood into early adulthood in individuals with developmental coordination disorder (DCD) using a life course health development framework. One systematic review was conducted, and four original research studies produced with retrospective data from four unique cohorts in childhood, adolescence, and adulthood. Physical activity was assessed via accelerometry in Finnish child and adult populations and via self-reporting in an Australian population at 17 and 20 years. Bone was assessed via peripheral quantitative computed tomography in adolescents and dual energy x-ray absorptiometry in adults at age 20 years in two Australian cohorts. Bone was assessed cross-sectionally in the adult cohort and longitudinally over six months in adolescents. A mixed model statistical approach was used across studies to account for effects of known physical activity and bone confounders. Bone deficits were present in individuals with DCD until at least the time of peak bone mass and indicated to be related to reduced physical activity. DCD risk status was associated with deficits in physical activity across the lifespan that may relate to bone impairments, including reduced high impact peaks in boys (Mage=8.8 years) and increased sedentary light activity in adults aged 25 years. These patterns were influenced by other individual factors including individual motor skills and visuomotor impairment. Bone health improvements following engagement in an exercise program in adolescents showed that bone outcomes could be improved via osteogenic physical activity but also reinforced the importance of other aspects of movement on bone gains in this population. Bone deficits differed by sex in accordance with physical activity differences whereby males showed larger differences based on DCD status than females. Notably, bone deficits were seen in early adulthood for males only. Physical activity patterns were indicative of a cause for this sex-based difference, with a relationship between loading from physical activity and bone only seen in males. These findings have important implications for the health and clinical management of individuals with DCD by confirming the continued vulnerability of this population for osteoporosis risk and fracture however they also provide a potential avenue for improvement via physical activity and exercise engagement