Towards novel measurements of remodeling activity in cortical bone: implications for osteoporosis and related pharmaceutical treatments.

Bone remodelling is performed by basic multicellular units (BMUs) that resorb and subsequently form discrete packets of bone tissue. Normally, the resorption and formation phases of BMU activity are tightly coupled spatially and temporally to promote relatively stable bone mass and bone quality. However, dysfunctional remodelling can lead to bone loss and is the underlying cause of osteoporosis. This review surveys how BMU activity is altered in postmenopausal, disuse and glucocorticoid-induced osteoporosis as well as the impact of anabolic and anti-resorptive pharmaceutical treatments. The dysfunctional remodelling observed during disease and following medical intervention bares many testable hypotheses regarding the regulation of BMU activity and may provide novel insights that challenge existing paradigms of remodelling dynamics, particularly the poorly understood BMU coupling mechanisms. Most bone remodelling research has focused on trabecular bone and 2D analyses, as technical challenges limit the direct assessment of BMU activity in cortical bone. Recent advances in imaging technology present an opportunity to investigate cortical bone remodelling in vivo. This review discusses innovative experimental methods, such as 3D and 4D (i.e. time- lapsed) evaluation of BMU morphology and trajectory, that may be leveraged to improve the understanding of the spatio-temporal coordination of BMUs in cortical bone.

Homogeneous hydroxyapatite/alginate composite hydrogel promotes calcified cartilage matrix deposition with potential for three-dimensional bioprinting.

Calcified cartilage regeneration plays an important role in successful osteochondral repair, since it provides a biological and mechanical transition from the unmineralized cartilage at the articulating surface to the underlying mineralized bone. To biomimic native calcified cartilage in engineered constructs, here we test the hypothesis that hydroxyapatite (HAP) stimulates chondrocytes to secrete the characteristic matrix of calcified cartilage. Sodium citrate (SC) was added as a dispersant of HAP within alginate (ALG), and homogeneous dispersal of HAP within ALG hydrogel was confirmed using sedimentation tests, electron microscopy, and energy dispersive spectroscopy. To examine the biological performance of ALG/HAP composites, chondrocyte survival and proliferation, extracellular matrix production, and mineralization potential were evaluated in the presence or absence of the HAP phase. Chondrocytes in ALG/HAP constructs survived well and proliferated, but also expressed higher levels of calcified cartilage markers compared to controls, including Collagen type X secretion, alkaline phosphatase (ALP) activity, and mineral deposition. Compared to controls, ALG/HAP constructs also showed an elevated level of mineralized matrix in vivo when implanted subcutaneously in mice. The printability of ALG/HAP composite hydrogel precursors was verified by 3D printing of ALG/HAP hydrogel scaffolds with a porous structure. In summary, these results confirm the hypothesis that HAP in ALG hydrogel stimulates chondrocytes to secrete calcified matrix in vitro and in vivo and reveal that ALG/HAP composites have the potential for 3D bioprinting and osteochondral regeneration.

Skeletal Lead Burden of the British Royal Navy in Colonial Antigua.

Lead (Pb) has been known to be a cause of human poisoning since ancient times, but despite this, it was a widely used metal in the European colonial period. In this study, the relationship between Pb exposure and the demographic variables ancestry and age was explored by comparing the bone Pb levels of individuals that were of either African or European ancestry, excavated from a British Royal Navy hospital cemetery (1793-1822 CE) at English Harbour in Antigua, West Indies. More direct comparisons of Pb levels between the two ancestral groups were possible in this study because of the unsegregated nature of this cemetery. Inductively coupled plasma mass spectrometry was used to determine bulk Pb levels in cortical bone samples from the fibular diaphyses of 23 male individuals. No significant difference was found between the distributions of the Pb levels of the ancestral groups (p = 0.94). Further, no positive correlations or significant differences were found in relation to the individuals' ages and their Pb levels (p = 0.24). Levels of Ba, Ca and rare earth elements support a largely biogenic origin of lead. This is bolstered by Pb deposition patterns, generated by synchrotron X-ray fluorescence imaging for another study. The data suggest that naval personnel, regardless of ancestry at English Harbour, had very similar experiences with regard to Pb exposure. Their exposure to the toxic metal was likely not consistent over time as steady exposure would have resulted in accumulation of Pb with age. This study contributes to addressing historical questions regarding the prevalence of Pb poisoning within the British Royal Navy during the colonial period.

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.

Cortical Bone Porosity: What Is It, Why Is It Important, and How Can We Detect It?

There is growing recognition of the role of micro-architecture in osteoporotic bone loss and fragility. This trend has been driven by advances in imaging technology, which have enabled a transition from measures of mass to micro-architecture. Imaging trabecular bone has been a key research focus, but advances in resolution have also enabled the detection of cortical bone micro-architecture, particularly the network of vascular canals, commonly referred to as 'cortical porosity.' This review aims to provide an overview of what this level of porosity is, why it is important, and how it can be characterized by imaging. Moving beyond a 'trabeculocentric' view of bone loss holds the potential to improve diagnosis and monitoring of interventions. Furthermore, cortical porosity is intimately linked to the remodeling process, which underpins bone loss, and thus a larger potential exists to improve our fundamental understanding of bone health through imaging of both humans and animal models.

Role of endocortical contouring methods on precision of HR-pQCT-derived cortical micro-architecture in postmenopausal women and young adults.

UNLABELLED: Precision errors of cortical bone micro-architecture from high-resolution peripheral quantitative computed tomography (pQCT) ranged from 1 to 16 % and did not differ between automatic or manually modified endocortical contour methods in postmenopausal women or young adults. In postmenopausal women, manually modified contours led to generally higher cortical bone properties when compared to the automated method. INTRODUCTION: First, the objective of the study was to define in vivo precision errors (coefficient of variation root mean square (CV%RMS)) and least significant change (LSC) for cortical bone micro-architecture using two endocortical contouring methods: automatic (AUTO) and manually modified (MOD) in two groups (postmenopausal women and young adults) from high-resolution pQCT (HR-pQCT) scans. Second, it was to compare precision errors and bone outcomes obtained with both methods within and between groups. METHODS: Using HR-pQCT, we scanned twice the distal radius and tibia of 34 postmenopausal women (mean age ± SD 74 ± 7 years) and 30 young adults (27 ± 9 years). Cortical micro-architecture was determined using AUTO and MOD contour methods. CV%RMS and LSC were calculated. Repeated measures and multivariate ANOVA were used to compare mean CV% and bone outcomes between the methods within and between the groups. Significance was accepted at P < 0.05. RESULTS: CV%RMS ranged from 0.9 to 16.3 %. Within-group precision did not differ between evaluation methods. Compared to young adults, postmenopausal women had better precision for radial cortical porosity (precision difference 9.3 %) and pore volume (7.5 %) with MOD. Young adults had better precision for cortical thickness (0.8 %, MOD) and tibial cortical density (0.2 %, AUTO). In postmenopausal women, MOD resulted in 0.2-54 % higher values for most cortical outcomes, as well as 6-8 % lower radial and tibial cortical BMD and 2 % lower tibial cortical thickness. CONCLUSIONS: Results suggest that AUTO and MOD endocortical contour methods provide comparable repeatability. In postmenopausal women, manual modification of endocortical contours led to generally higher cortical bone properties when compared to the automated method, while no between-method differences were observed in young adults.

Structural Characterization of Sm(III)(EDTMP).

Samarium-153 ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid) ((153)Sm-EDTMP, or samarium lexidronam), also known by its registered trademark name Quadramet, is an approved therapeutic radiopharmaceutical used in the palliative treatment of painful bone metastases. Typically, patients with prostate, breast, or lung cancer are most likely to go on to require bone pain palliation treatment due to bone metastases. Sm(EDTMP) is a bone-seeking drug which accumulates on rapidly growing bone, thereby delivering a highly region-specific dose of radiation, chiefly through ß particle emission. Even with its widespread clinical use, the structure of Sm(EDTMP) has not yet been characterized at atomic resolution, despite attempts to crystallize the complex. Herein, we prepared a 1:1 complex of the cold (stable isotope) of Sm(EDTMP) under alkaline conditions and then isolated and characterized the complex using conventional spectroscopic techniques, as well as with extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional structure calculations, using natural abundance Sm. We present the atomic resolution structure of [Sm(III)(EDTMP)-8H](5-) for the first time, supported by the EXAFS data and complementary spectroscopic techniques, which demonstrate that the samarium coordination environment in solution is in agreement with the structure that has long been conjectured.

In vivo imaging of rat cortical bone porosity by synchrotron phase contrast micro computed tomography.

Cortical bone is a dynamic tissue which undergoes adaptive and pathological changes throughout life. Direct longitudinal tracking of this remodeling process holds great promise for improving our understanding of bone development, maintenance and senescence. The application of in vivo micro-computed tomography (micro-CT) has enabled longitudinal tracking of trabecular bone microarchitecture with commercially available scanners generally operating in the 10-20 µm voxel range with absorbed doses reported between 0.5 and 1 Gy. Imaging of cortical bone microarchitecture (porosity) requires higher resolution and thus in vivo imaging of these structures has not been achieved due to excessive radiation dose. In this study we tested the hypothesis that synchrotron propagation phase contrast micro-CT can enable in vivo imaging of cortical porosity in rats at doses comparable to those currently employed for trabecular bone imaging. Synchrotron imaging experiments were conducted at the Canadian Light Source using the bending magnet beamline of the BioMedical Imaging and Therapy (BMIT) facility. Protocol optimization (propagation distance, projection number) was conducted ex vivo on rat (Sprague-Dawley) forelimbs with dose determined by ion chamber and lithium fluoride crystal thermoluminescent dosimeters. Comparative ex vivo imaging was performed using laboratory in vivo scanning systems, identifying a range of doses between 1.2-3.6 Gy for common protocols. A final in vivo synchrotron protocol involving a 2.5 Gy dose was implemented with live rats. The resulting images demonstrated improved delineation of cortical porosity through the improved edge enhancement effect of phase contrast, opening the door to novel experimental studies involving the longitudinal tracking of remodeling.

Point taken: An unusual case of incisor agenesis and mandibular trauma in Early Bronze Age Siberia.

This paper focuses on the mandible of an adult male individual (radiocarbon dated to 4420-3995cal BP) from the Early Bronze Age Cis-Baikal cemetery of Ust'-Ida I (Siberia, Russian Federation). The mandible contains two features of interest: (1) bilaterally missing central incisors, and (2) the tip of a lithic projectile point embedded in the symphyseal region. Despite the absent teeth, the mandible presents a dental arcade without diastemata, appearing normal and complete on first glance. Three different levels of CT (computed tomography) imaging-ranging from clinical to synchrotron-based-were employed in order to establish the aetiology behind the missing dentition, whether subsequent to the projectile trauma or entirely unrelated to it. Results indicate that the mandible exhibits two highly unusual but unrelated features: probable bilateral agenesis of the central incisors and perimortem trauma to the mental symphysis. In addition, the embedded tip was successfully matched via digital imaging to photographs of a broken projectile point, an artefact recovered from the facial region of the skeleton.

Does frequency of resistance training affect tibial cortical bone density in older women? A randomized controlled trial.

SUMMARY: This randomized controlled trial evaluated the effect of resistance training frequency (0, 1, and 2 times/week) on cortical volumetric bone mineral density (vBMD) at the tibia in older women. There was no mean difference in change in tibial cortical vBMD in older women who engaged in resistance training (RT) one or two times/week compared with the control group over 12 months after adjusting for baseline values. INTRODUCTION: National guidelines recommend RT two to three times/week to optimize bone health. Our objective was to determine the effect of a 12-month intervention of three different RT frequencies on tibial volumetric cortical density (CovBMD) in healthy older women. METHODS: We randomized participants to the following groups: (1) 2×/week balance and tone group (i.e., no resistance beyond body weight, BT), (2) 1×/week RT (RT1), and (3) 2×/week RT (RT2). Treatment allocation was concealed, and measurement team and the bone data analyst were blinded to group allocation. We used peripheral quantitative computed tomography to acquire one 2.3-mm scan at the 50 % tibia, and the primary outcome was CovBMD. Data were collected at baseline, 6 and 12 months, and we used linear mixed modeling to assess the effect at 12 months. RESULTS: We assessed 147 participants; 100 women provided data at all three points. Baseline unadjusted mean (SD) tibial CovBMD (in milligrams per cubic centimeter) at the 50 % site was 1,077.4 (43.0) (BT), 1,087.8 (42.0) (RT1), and 1,058.7 (60.4) (RT2). At 12 months, there were no statistically significant differences (-0.45 to -0.17 %) between BT and RT groups for mean difference in change in tibial CovBMD for exercise interventions (BT, RT1, RT2) after adjusting for baseline tibial CovBMD. CONCLUSION: We note no mean difference in change in tibial CovBMD in older women who engaged in RT one or two times/week compared with the control group over 12 months. It is unknown if RT of 3× or 4×/week would be enough to promote a statistically significant difference in change of bone density.

Three dimensional mapping of strontium in bone by dual energy K-edge subtraction imaging.

The bones of many terrestrial vertebrates, including humans, are continually altered through an internal process of turnover known as remodeling. This process plays a central role in bone adaptation and disease. The uptake of fluorescent tetracyclines within bone mineral is widely exploited as a means of tracking new tissue formation. While investigation of bone microarchitecture has undergone a dimensional shift from 2D to 3D in recent years, we lack a 3D equivalent to fluorescent labeling. In the current study we demonstrate the ability of synchrotron radiation dual energy K-edge subtraction (KES) imaging to map the 3D distribution of elemental strontium within rat vertebral samples. This approach has great potential for ex vivo analysis of preclinical models and human tissue samples. KES also represents a powerful tool for investigating the pharmokinetics of strontium-based drugs recently approved in many countries around the globe for the treatment of osteoporosis.

Relating age and micro-architecture with apparent-level elastic constants: a micro-finite element study of female cortical bone from the anterior femoral midshaft.

Homogenized elastic properties are often assumed for macro-finite element (FE) models used in orthopaedic biomechanics. The accuracy of material property assignments may have a strong effect on the ability of these models to make accurate predictions. For cortical bone, most macro-scale FE models assume isotropic elastic material behaviour and do not include variation of material properties due to bone micro-architecture. The first aim of the present study was to evaluate the variation of apparent-level (homogenized) orthotropic elastic constants of cortical bone with age and indices of bone micro-architecture. Considerable age-dependent differences in porosity were noted across the cortical thickness in previous research. The second aim of the study was to quantify the resulting differences in elastic constants between the periosteum and endosteum. Specimens were taken from the anterior femoral midshaft of 27 female donors (age 53.4 +/- 23.6 years) and micro-FE (gFE) analysis was used to derive orthotropic elastic constants. The variation of orthotropic elastic constants (Young's moduli, shear moduli, and Poisson's ratios) with various cortical bone micro-architectural indices was investigated. The ratio of canal volume to tissue volume, Ca.V/TV, analogous to porosity, was found to be the strongest predictor (r2(ave) = 0.958) of the elastic constants. Age was less predictive (r2(ave) = 0.385) than Ca.V/TV. Elastic anisotropy increased with increasing Ca.V/TV, leading to lower elastic moduli in the transverse, typically less frequently loaded, directions. Increased Ca.V/TV led to a more substantial reduction in elastic constants at the endosteal aspect than at the periosteal aspect. The results are expected to be most applicable in similar midshaft locations of long bones; specific analysis of other sites would be necessary to evaluate elastic properties elsewhere. It was concluded that Ca.V/TV was the most predictive of cortical bone elastic constants and that considerable periosteal-endosteal variations in these constants can develop with bone loss.

Imaging the 3D structure of secondary osteons in human cortical bone using phase-retrieval tomography.

By applying a phase-retrieval step before carrying out standard filtered back-projection reconstructions in tomographic imaging, we were able to resolve structures with small differences in density within a densely absorbing sample. This phase-retrieval tomography is particularly suited for the three-dimensional segmentation of secondary osteons (roughly cylindrical structures) which are superimposed upon an existing cortical bone structure through the process of turnover known as remodelling. The resulting images make possible the analysis of the secondary osteon structure and the relationship between an osteon and the surrounding tissue. Our observations have revealed many different and complex 3D structures of osteons that could not be studied using previous methods. This work was carried out using a laboratory-based x-ray source, which makes obtaining these sorts of images readily accessible.

Visualization of 3D osteon morphology by synchrotron radiation micro-CT.

Cortical bone histology has been the subject of scientific inquiry since the advent of the earliest microscopes. Histology - literally the study of tissue - is a field nearly synonymous with 2D thin sections. That said, progressive developments in high-resolution X-ray imaging are enabling 3D visualization to reach ever smaller structures. Micro-computed tomography (micro-CT), employing conventional X-ray sources, has become the gold standard for 3D analysis of trabecular bone and is capable of detecting the structure of vascular (osteonal) porosity in cortical bone. To date, however, direct 3D visualization of secondary osteons has eluded micro-CT based upon absorption-derived contrast. Synchrotron radiation micro-CT, through greater image quality, resolution and alternative contrast mechanisms (e.g. phase contrast), holds great potential for non-destructive 3D visualization of secondary osteons. Our objective was to demonstrate this potential and to discuss areas of bone research that can be advanced through the application of this approach. We imaged human mid-femoral cortical bone specimens derived from a 20-year-old male (Melbourne Femur Collection) at the Advanced Photon Source synchrotron (Chicago, IL, USA) using the 2BM beam line. A 60-mm distance between the target and the detector was employed to enhance visualization of internal structures through propagation phase contrast. Scan times were 1 h and images were acquired with 1.4-µm nominal isotropic resolution. Computer-aided manual segmentation and volumetric 3D rendering were employed to visualize secondary osteons and porous structures, respectively. Osteonal borders were evident via two contrast mechanisms. First, relatively new (hypomineralized) osteons were evident due to differences in X-ray attenuation relative to the surrounding bone. Second, osteon boundaries (cement lines) were delineated by phase contrast. Phase contrast also enabled the detection of soft tissue remnants within the vascular pores. The ability to discern osteon boundaries in conjunction with vascular and cellular porosity revealed a number of secondary osteon morphologies and provided a unique 3D perspective of the superimposition of secondary osteons on existing structures. Improvements in resolution and optimization of the propagation phase contrast promise to provide further improvements in structural detail in the future.

3D visualization and quantification of rat cortical bone porosity using a desktop micro-CT system: a case study in the tibia.

Although micro-computed tomography (micro-CT) has become the gold standard for assessing the 3D structure of trabecular bone, its extension to cortical bone microstructure has been relatively limited. Desktop micro-CT has been employed to assess cortical bone porosity of humans, whereas that of smaller animals, such as mice and rats, has thus far only been imaged using synchrotron-based micro-CT. The goal of this study was to determine if it is possible to visualize and quantify rat cortical porosity using desktop micro-CT. Tibiae (n = 10) from 30-week-old female Sprague-Dawley rats were imaged with micro-CT (3 µm nominal resolution) and sequential ground sections were then prepared. Bland-Altman plots were constructed to compare per cent porosity and mean canal diameter from micro-CT (3D) versus histology (2D). The mean difference or bias (histology-micro-CT; ±95% confidence interval) for per cent porosity was found to be -0.15% (±2.57%), which was not significantly different from zero (P= 0.720). Canal diameter had a bias (±95% confidence interval) of -5.73 µm (±4.02 µm) which was found to be significantly different from zero (P < 0.001). The results indicated that cortical porosity in rat bone can indeed be visualized by desktop micro-CT. Quantitative assessment of per cent porosity provided unbiased results, whereas direct analysis of mean canal diameter was overestimated by micro-CT. Thus, although higher resolution, such as that available from synchrotron micro-CT, may ultimately be required for precise geometric measurements, desktop micro-CT--which is far more accessible--is capable of yielding comparable measures of porosity and holds great promise for assessment of the 3D arrangement of cortical porosity in the rat.

Anterior-posterior bending strength at the tibial shaft increases with physical activity in boys: evidence for non-uniform geometric adaptation.

UNLABELLED: We investigated bone structural adaptations to a 16-month school-based physical activity intervention in 202 young boys using a novel analytical method for peripheral quantitative computed tomography scans of the tibial mid-shaft. Our intervention effectively increased bone bending strength in the anterior-posterior plane as estimated with the maximum second moment of area (I(max)). INTRODUCTION: We previously reported positive effects of a physical activity intervention on peripheral quantitative computed tomography (pQCT)-derived bone strength at the tibial mid-shaft in young boys. The present study further explored structural adaptations to the intervention using a novel method for pQCT analysis. METHODS: Participants were 202 boys (aged 9-11 years) from 10 schools randomly assigned to control (CON, 63 boys) and intervention (INT, 139 boys) groups. INT boys participated in 60 min/week of classroom physical activity, including a bone-loading program. We used ImageJ to process pQCT images of the tibial mid-shaft and determine the second moments of area (I(max), I(min)) and cortical area (CoA) and thickness (CTh) by quadrant (anterior, medial, lateral, posterior). We defined quadrants according to pixel coordinates about the centroid. We used mixed linear models to compare change in bone outcomes between groups. RESULTS: The INT boys had a 3% greater gain in I(max) than the CON boys (p = 0.04) and tended to have a greater gain in I(min) ( approximately 2%, NS). Associated with the greater gain in I(max) was a slightly greater (NS) gain (1-1.4%) in CoA and CTh in the anterior, medial, and posterior (but not lateral) quadrants. CONCLUSION: Our results suggest regional variation in bone adaptation consistent with patterns of bone formation induced by anterior-posterior bending loads.

Cortical and trabecular bone in the femoral neck both contribute to proximal femur failure load prediction.

UNLABELLED: We examined the contributions of femoral neck cortical and trabecular bone to proximal femur failure load. We found that trabecular bone mineral density explained a significant proportion of variance in failure load after accounting for total bone size and cortical bone mineral content or cortical area. INTRODUCTION: The relative contribution of femoral neck trabecular and cortical bone to proximal femur failure load is unclear. OBJECTIVES: Our primary objective was to determine whether trabecular bone mineral density (TbBMD) contributes to proximal femur failure load after accounting for total bone size and cortical bone content. Our secondary objective was to describe regional differences in the relationship among cortical bone, trabecular bone, and failure load within a cross-section of the femoral neck. MATERIALS AND METHODS: We imaged 36 human cadaveric proximal femora using quantitative computed tomography (QCT). We report total bone area (ToA), cortical area (CoA), cortical bone mineral content (CoBMC), and TbBMD measured in the femoral neck cross-section and eight 45 degrees regions. The femora were loaded to failure. RESULTS AND OBSERVATIONS: Trabecular bone mineral density explained a significant proportion of variance in failure load after accounting for ToA and then either CoBMC or CoA respectively. CoBMC contributed significantly to failure load in all regions of the femoral neck except the posterior region. TbBMD contributed significantly to failure load in all regions of the femoral neck except the inferoanterior, superoposterior, and the posterior regions. CONCLUSION: Both cortical and trabecular bone make significant contributions to failure load in ex vivo measures of bone strength.

Ontogenetic patterning of cortical bone microstructure and geometry at the human mid-shaft femur.

The bone growth process has long-lasting effects on adult bone structure and mechanical adaptation, yet the tissue level dynamics of growth are poorly studied. The specific aims of this study were to (1) quantify changes in bone size and shape through ontogeny, (2) describe the distribution of tissue types and patterns of cortical drift and expansion through ontogeny, and (3) explore relationships between cortical drift and ontogenetic variation geometric size and shape. The study utilized 14 juvenile (ages 2-19) mid-shaft femur blocks removed at autopsy from individuals who died suddenly. Eighty-mum-thick sections were imaged using polarized and brightfield microscopy. For descriptive purposes the sample was divided into five age groups. Features of collagen fiber matrix orientation, vascularity (e.g., pore orientation and density), and osteocyte lacunar density and shape were used to classify primary and secondary tissue types in LM images. This information, combined with evaluation of resorptive versus depositional bone surfaces, was used to identify cortical drift direction. A pattern of posterior and medial drift was identified at the mid-shaft femur in the toddler years. The drift pattern shifts antero-laterally in late childhood, predating the appearance of a more adult-like geometry. On the basis of the presence of transitional fibrolamellar bone complex, growth is more rapid during the toddler years and peri-puberty, and slower in early to late childhood and in later adolescence. Extensive variability in histological and geometric organization typifies the sample, particularly beginning in late childhood. The potential implications of this variability for adult fracture risk warrant further study. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.

Characterising cortical density in the mid-tibia: intra-individual variation in adolescent girls and boys.

BACKGROUND: Inter-individual differences in cortical bone volumetric density (CoD), such as those related to sex, are a product of differences in remodelling rates. While cortical bone is often treated as a uniform tissue, remodelling rates also vary within individual bones. This level of adaptation has largely been overlooked in analyses of peripheral quantitative computed tomography (pQCT) images. Further, such variation in CoD has never been assessed in growing bones. We hypothesised that CoD varied significantly within the same cross-section of the mid-tibia of adolescents. We further hypothesised that due to the profound impact of oestrogen on remodelling, this variation would be different between sexes. METHODS: Subjects were 183 adolescents (99 girls and 84 boys) in grade 6 and 7 with a mean age of 12.1 years. We used age at peak height velocity to adjust for maturational differences between sexes. Image data from a mid-tibia pQCT scan of each subject were assessed regionally within eight sectors distributed about the cortex and aligned by the anterior tibial crest. We used a repeated measures general linear model to assess intra-individual variation in CoD while controlling for differences in ethnicity, maturity, height, weight, physical activity level and total cross-sectional bone area (ToA). RESULTS: Sector based variation in CoD was significant (p<0.001), with the anterior cortex having lower density than the posterior cortex. The largest percentage difference (anterior vs posteromedial sectors) was 12.2%. A significant sector*sex interaction (p = 0.018) was detected; however, its impact was relatively small with girls having 1.1-3.6% denser bones than boys depending on the sector (2.7% average difference). CONCLUSIONS: The magnitude of the variation in CoD across sectors within individuals of both sex was far greater than the mean differences between the sexes. This finding indicates that the microstructural variation within the mid-tibia is detectable by pQCT and its magnitude suggests an important level of adaptation to loading.

Muscle power is related to tibial bone strength in older women.

UNLABELLED: We enrolled 65 to 75 year-old community-dwelling women and measured muscle power, strength, physical activity using accelerometry and tibial bone strength using peripheral quantitative computed tomography (pQCT). Muscle power contributed 6.6% of the variance in the bone strength-strain index and 8.9% in the section modulus after accounting for age, height, weight, and physical activity; moderate to vigorous physical activity was related to muscle power in the lower extremity. INTRODUCTION: Muscle power is associated with DXA measurements of bone mass, but it is not known whether muscle power is associated with bone strength. There are no reports of investigations that have tested the effect of muscle power on bone compartments using advanced imaging. METHODS: We enrolled 74 community-dwelling women aged 65-75 years. We measured muscle power and strength of leg extension using Keiser air-pressure resistance equipment. All participants wore a waist-mounted Actigraph accelerometer to record physical activity. We used peripheral quantitative computed tomography (pQCT) to measure tibial mid-shaft (50% of the site) bone strength (strength-strain index, section modulus). We used Pearson correlations and multi-level linear regression to investigate the associations between muscle and bone. RESULTS: Muscle power contributed 6.6% (p = 0.007) of the variance in the bone strength-strain index and 8.9% (p = 0.001) the variance in the section modulus in older women after accounting for age, height, weight, and physical activity. Moderate to vigorous physical activity was significantly related to muscle power in the lower extremity (r = 0.260; p = 0.041). CONCLUSION: Muscle power significantly contributed to the variance in estimated bone strength. Whether power training will prove to be a more effective stimulus for bone strength than conventional strength training will require further studies.