Modelling the Effects of Growth and Remodelling on the Density and Structure of Cancellous Bone.

A two-stage model is proposed for investigating remodelling characteristics in bone over time and distance to the growth plate. The first stage comprises a partial differential equation (PDE) for bone density as a function of time and distance from the growth plate. This stage clarifies the contributions to changes in bone density due to remodelling and growth processes and tracks the rate at which new bone emanates from the growth plate. The second stage consists of simulating the remodelling process to determine remodelling characteristics. Implementing the second stage requires the rate at which bone moves away from the growth plate computed during the first stage. The second stage is also needed to confirm that remodelling characteristics predicted by the first stage may be explained by a realistic model for remodelling and to compute activation frequency. The model is demonstrated on microCT scans of tibia of juvenile female rats in three experimental groups: sham-operated control, oestrogen deprived, and oestrogen deprived followed by treatment. Model predictions for changes in bone density and remodelling characteristics agree with the literature. In addition, the model provides new insight into the role of treatment on the density of new bone emanating from the growth plate and provides quantitative descriptions of changes in remodelling characteristics beyond what has been possible to ascertain by experimentation alone.

Modic (endplate) changes in the lumbar spine: bone micro-architecture and remodelling.

PURPOSE: In the literature, inter-vertebral MRI signal intensity changes (Modic changes) were associated with corresponding histological observations on endplate biopsies. However, tissue-level studies were limited. No quantitative histomorphometric study on bone biopsies has yet been conducted for Modic changes. The aim of this study was to characterise the bone micro-architectural parameters and bone remodelling indices associated with Modic changes. METHODS: Forty patients suffering from disabling low back pain, undergoing elective spinal surgery, and exhibiting Modic changes on MRI (Modic 1, n = 9; Modic 2, n = 25; Modic 3, n = 6), had a transpedicular vertebral body biopsy taken of subchondral bone. Biopsies were first examined by micro-CT, for 3D morphometric analysis of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation, trabecular number, and structure model index. Then, samples underwent histological analysis, for determination of bone remodelling indices: osteoid surface to bone surface ratio (OS/BS), eroded surface to bone surface (ES/BS) and osteoid surface to eroded surface ratio (OS/ES). RESULTS: Micro-CT analysis revealed significantly higher BV/TV (up to 70% increase, p < 0.01) and Tb.Th (up to +57%, p < 0.01) in Modic 3 biopsies, compared to Modic 1 and 2. Histological analysis showed significantly lower OS/BS in Modic 2 biopsies (more than 28% decrease, p < 0.05) compared to 1 and 3. ES/BS progressively decreased from Modic 1 to 2 to 3, whereas OS/ES progressively increased with significantly higher values in Modic 3 (up to 159% increase, p < 0.05) than in Modic 1 and 2. CONCLUSIONS: Significant differences were found in bone micro-architectural parameters and remodelling indices among Modic types. Modic 1 biopsies had evidence of highest bone turnover, possibly due to an inflammatory process; Modic 2 biopsies were consistent with a reduced bone formation/remodelling stage; Modic 3 biopsies suggested a more stable sclerotic phase, with significantly increased BV/TV and Tb.Th compared to Modic 1 and 2, linked to increased bone formation and reduced resorption.

Anti-osteoporosis therapy and fracture healing.

BACKGROUND: A number of medications are approved for treatment of osteoporosis. As mode of action usually is anti-catabolic/anti-resorptive or anabolic, it is of interest to know whether these drugs affect not only normal bone remodeling, but also fracture healing. OBJECTIVE: The purpose of this paper is to give a short overview of the potential effect of various anti-osteoporotic medication on fracture healing. METHODS: A narrative literature review was performed to describe the current knowledge. RESULTS: Anti-catabolic/anti-resorptive drugs: for bisphosphonates, the most common class of drugs in this group, experimental studies have shown a larger and stronger callus and delayed remodeling but no evidence of delayed healing. A human monoclonal antibody to RANKL is another anti-catabolic drug, with the only report to date showing enhanced healing in an animal model. Strontium ranelate is a drug where both anti-catabolic and a weak anabolic effect have been proposed, with experimental data ranging from no effect to significant increase in both callus volume and strength. Anabolic drugs: PTH has demonstrated accelerated healing of various experimental fractures and of distal radius and pelvic fractures in humans. While the exact mechanism is not fully understood, PTH results in increased recruitment and differentiation of chondrocytes and enhancement of endochondral ossification. A monoclonal antibody to block sclerostin is another potential anabolic pathway, where animal data have shown increase in bone mass and strength. The potential effect on fracture healing is yet to be studied. CONCLUSION: There are still large gaps in the understanding of the potential effect of anti-osteoporotic drugs on fracture healing, although based on present knowledge a recent or present fracture should not be considered as a contraindication to such treatment.

Temporal changes in bone composition, architecture, and strength following estrogen deficiency in osteoporosis.

Using an ovariectomized (OVX) ovine model, we provide an analysis of the timing of changes in bone following estrogen deficiency. The expression of genes known to regulate osteoclastogenesis, matrix production, and mineralization, as measured by real-time RT-PCR, was significantly increased by 12 months; and increased expression was maintained through to 31 months post-OVX compared to controls. FTIR spectroscopy confirmed that mineralized crystals were less mature than in controls 12 months post-OVX and were even less so by 31 months. The mineral-to-matrix ratio was significantly reduced by 31 months, while the ratio of mature to immature collagen cross-linking was initially increased at 12 months and subsequently reduced at 31 months post-OVX. In contrast, trabecular number, thickness, and separation were unchanged at 12 months. Significant reductions in trabecular number and thickness and a significant increase in trabecular separation were observed 31 months after OVX. Most notably perhaps these combined changes led to a significant reduction in the compressive strength of trabecular bone after 31 months. The results indicate that there is an initial increase in bone turnover, which is accompanied by a change in bone composition. This is followed by a continued increase in bone resorption and relative reduction in bone formation, leading to deterioration in bone microarchitecture. Ultimately, these cumulative changes led to a significant reduction in the compressive strength of bones following 31 months of estrogen deficiency. These findings provide important insight into the time sequence of changes during osteoporosis.

Measurement of subregional vertebral bone mineral density in vitro using lateral projection dual-energy X-ray absorptiometry: validation with peripheral quantitative computed tomography.

Although a strong relationship exists between areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) and bone strength, the predictive validity of aBMD for osteoporotic vertebral fractures remains suboptimal. The diagnostic sensitivity of DXA may be improved by assessing aBMD within vertebral subregions, rather than relying on an estimate derived from the total area of the vertebra. The objective of this study was to validate a method of measuring subregional vertebral aBMD in vitro using lateral-projection DXA against subregional volumetric BMD (vBMD) measured with peripheral quantitative computed tomography (pQCT). A mixed set of 49 lumbar and thoracic vertebrae from 25 donors were scanned using lateral-projection DXA and pQCT. aBMD and apparent vBMD were measured in 7 vertebral regions (1 total area and 6 subregions) from the lateral DXA scan. vBMD was calculated in anatomically equivalent regions from pQCT scan data, using a customised software program designed to increase efficiency of the analysis process. Significant differences in densitometric parameters between subregions were observed by DXA and pQCT (P < 0.01). Subregional vBMD derived from pQCT was explained by a significant proportion of the variance in DXA-derived aBMD (R (2) = 0.51-0.67, P < 0.05) and apparent vBMD (R (2) = 0.64-0.75, P < 0.05). These results confirm the validity of measuring aBMD in vertebral subregions using lateral-projection DXA. The clinical significance should now be explored.

Osteocyte apoptosis and lipid infiltration as mechanisms of alcohol-induced bone loss.

AIMS: We carried out an in vivo study to assess the relationship between increase in adiposity in the marrow and osteocyte apoptosis in the case of alcohol-induced bone loss. METHODS AND RESULTS: After alcohol treatment, the number of apoptotic osteocytes was increased and lipid droplets were accumulated within the osteocytes, the bone marrow and the cortical bone micro-vessels. At last, we found an inverse correlation between bone mineral density and osteocyte apoptosis and strong significant correlations between the osteocyte apoptotic number and lipid droplet accumulation in osteocyte and bone micro-vessels. CONCLUSION: These data show that alcohol-induced bone loss is associated with osteocyte apoptosis and lipid accumulation in the bone tissue. This lipid intoxication, or 'bone steatosis', is correlated with lipid accumulation in bone marrow and blood micro-vessels.

An update on primary hip osteoarthritis including altered Wnt and TGF-ß associated gene expression from the bony component of the disease.

The study of primary hip OA is continuing to redefine what was once considered a stagnant pathology as one of dynamic change, occurring over a long period of time involving the many composite tissue types of the joint including the bone. Examination of the inverse relationships evident between OA and fracture cohorts, including individuals with osteoporosis (OP), indicates an imbalance in formation and resorption in the bony component of both pathologies. This review contains an overview of primary OA followed by an assessment of differential gene expression and altered cellular characteristics identified in the bony compartments of primary hip OA, with a focus on the wingless mouse mammary tumor virus integration (Wnt) and TGF-ß signalling pathways. The studies reviewed here suggest that OA is a systemic disease involving the bone and validate the assessment of molecular changes to further investigate this complex disease.

In vitro evaluation of a manganese chloride phantom-based MRI technique for quantitative determination of lumbar intervertebral disc composition and condition.

The application of MRI as a non-invasive, quantitative tool for diagnosing lumbar intervertebral disc degeneration is currently an area of active research. The objective of this study was to examine, in vitro, the efficacy of a manganese chloride phantom-based MRI technique for quantitatively assessing lumbar disc composition and degenerative condition. Sixteen human lumbar discs were imaged ex vivo using T2-weighted MRI, and assigned a quantitative grade based on the relative signal intensities of nine phantoms containing serial concentrations of manganese chloride. Discs were then graded macroscopically for degenerative condition, and water and uronic acid (glycosaminoglycan) contents were determined. MRI ranking exhibited significant and strong negative correlation with nucleus pulposus uronic acid content (r = -0.78). MRI grades were significantly higher for degenerate discs. The technique described presents immediate potential for in vitro studies requiring robust, minimally invasive and quantitative determination of lumbar disc composition and condition. Additionally, the technique may have potential as a clinical tool for diagnosing lumbar disc degeneration as it provides a standardised series of reference phantoms facilitating cross-platform consistency, requires short scan times and simple T2-weighted signal intensity measurements.

Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo.

Resident macrophages are an integral component of many tissues and are important in homeostasis and repair. This study examines the contribution of resident tissue macrophages to bone physiology. Using immunohistochemistry, we showed that a discrete population of resident macrophages, OsteoMacs, was intercalated throughout murine and human osteal tissues. OsteoMacs were distributed among other bone lining cells within both endosteum and periosteum. Furthermore, OsteoMacs were coisolated with osteoblasts in murine bone explant and calvarial preparations. OsteoMacs made up 15.9% of calvarial preparations and persisted throughout standard osteoblast differentiation cultures. Contrary to previous studies, we showed that it was OsteoMacs and not osteoblasts within these preparations that responded to pathophysiological concentrations of LPS by secreting TNF. Removal of OsteoMacs from calvarial cultures significantly decreased osteocalcin mRNA induction and osteoblast mineralization in vitro. In a Transwell coculture system of enriched osteoblasts and macrophages, we demonstrated that macrophages were required for efficient osteoblast mineralization in response to the physiological remodeling stimulus, elevated extracellular calcium. Notably, OsteoMacs were closely associated with areas of bone modeling in situ, forming a distinctive canopy structure covering >75% of mature osteoblasts on diaphyseal endosteal surfaces in young growing mice. Depletion of OsteoMacs in vivo using the macrophage-Fas-induced apoptosis (MAFIA) mouse caused complete loss of osteoblast bone-forming surface at this modeling site. Overall, we have demonstrated that OsteoMacs are an integral component of bone tissues and play a novel role in bone homeostasis through regulating osteoblast function. These observations implicate OsteoMacs, in addition to osteoclasts and osteoblasts, as principal participants in bone dynamics.

Novel assessment of subregional bone mineral density using DXA and pQCT and subregional microarchitecture using micro-CT in whole human vertebrae: applications, methods, and correspondence between technologies.

In the clinical environment dual-energy X-ray absorptiometry (DXA) is the current tool of first choice for assessing and monitoring skeletal integrity. A major drawback of standard DXA is that the bone mineral density (BMD) data cannot be used with certainty to predict who will sustain a vertebral fracture. However, measurement of BMD within vertebral subregions, instead of relying on a gross estimate of vertebral BMD, may improve diagnostic sensitivity. The aim of this article was to describe a validation study for subregional BMD measurement using lateral-projection DXA and to present preliminary data. Concurrent validity of measuring subregional BMD with DXA was established against measures of volumetric subregional BMD from peripheral quantitative computed tomography (pQCT) and subregional bone volume fraction from microCT at the L2 vertebral body in 8 cadaver spine specimens. The novel approaches for measuring subregional parameters with each imaging modality are described. Significant differences in bone parameters between vertebral subregions were observed for each imaging modality (p<0.05). Correspondence ranged from R(2)=0.01-0.79 and R(2)=0.06-0.80 between "DXA vs. pQCT" and "DXA vs. micro-CT," respectively. For both imaging modalities, correspondence with DXA was high for centrally and anteriorly positioned subregions. These data provide a basis for larger studies to examine the biological significance of heterogeneity in vertebral BMD.

The elastic fibre network of the human lumbar anulus fibrosus: architecture, mechanical function and potential role in the progression of intervertebral disc degeneration.

Elastic fibres are critical constituents of dynamic biological structures that functionally require elasticity and resilience. The network of elastic fibres in the anulus fibrosus of the intervertebral disc is extensive, however until recently, the majority of histological, biochemical and biomechanical studies have focussed on the roles of other extracellular matrix constituents such as collagens and proteoglycans. The resulting lack of detailed descriptions of elastic fibre network architecture and mechanical function has limited understanding of the potentially important contribution made by elastic fibres to healthy disc function and their possible roles in the progression of disc degeneration. In addition, it has made it difficult to postulate what the consequences of elastic fibre related disorders would be for intervertebral disc behaviour, and to develop treatments accordingly. In this paper, we review recent and historical studies which have examined both the structure and the function of the human lumbar anulus fibrosus elastic fibre network, provide a synergistic discussion in an attempt to clarify its potentially critical contribution both to normal intervertebral disc behaviour and the processes relating to its degeneration, and recommend critical areas for future research.

Determining disk hydration status with a MnCl2-based MR model.

PURPOSE: An extensive body of literature demonstrates a strong correlation between intervertebral disk (IVD) hydration status (HS) and functional spinal integrity. However, to date, in vivo IVD HS assessment has relied largely on subjective and nonrepeatable measures. The aim of this study was to establish the consistency of signal homogeneity of a novel semisolid-state manganese chloride (MnCl2)-based phantom for HS correlation using conventional magnetic resonance (MR) imaging. MATERIALS AND METHODS: Sixteen MnCl2 phantoms, of increasing relative molar concentration (range 0.01 to 2.9 mM), underwent axial MR imaging. Phantom signal-to-noise ratio measures were recorded for each concentration on several sequence types. Coefficient of variance data were calculated to determine the degree of MR signal variation at each concentration. RESULTS: Analysis of variance testing suggested no significant difference in coefficient of variance data derived from phantom signal intensities using either T1- (P = .13) or T2-weighted sequence types (P = .96), suggesting a high degree of relative signal homogeneity. CONCLUSIONS: The findings of this study suggest that a MnCl2 phantom combined with a nonfield reactive, semirigid, gelatin suspension media can produce a predictable, concentration-related, homogeneous MR signal response. This may be an appropriate base material for a noninvasive model to allow accurate quantification of the hydration status of the in vivo human IVD.

Influence of orthogonal overload on human vertebral trabecular bone mechanical properties.

UNLABELLED: The aim of this study was to investigate the effects of overload in orthogonal directions on longitudinal and transverse mechanical integrity in human vertebral trabecular bone. Results suggest that the trabecular structure has properties that act to minimize the decrease of apparent toughness transverse to the primary loading direction. INTRODUCTION: The maintenance of mechanical integrity and function of trabecular structure after overload remains largely unexplored. Whereas a number of studies have focused on addressing the question by testing the principal anatomical loading direction, the mechanical anisotropy has been overlooked. The aim of this study was to investigate the effects of overload in orthogonal directions on longitudinal and transverse mechanical integrity in human vertebral trabecular bone. MATERIALS AND METHODS: T(12)/L(1) vertebral bodies from five cases and L(4)/L(5) vertebral bodies from seven cases were retrieved at autopsy. A cube of trabecular bone was cut from the centrum of each vertebral body and imaged by microCT. Cubes from each T(12)/L(1) and L(4)/L(5) pairs were assigned to either superoinferior (SI) or anteroposterior (AP) mechanical testing groups. All samples were mechanically tested to 10% apparent strain by uniaxial compression according to their SI or AP allocation. To elucidate the extent to which overload in orthogonal directions affects the mechanical integrity of the trabecular structure, samples were retested (after initial uniaxial compression) in their orthogonal direction. After mechanical testing in each direction, apparent ultimate failure stresses (UFS), apparent elastic moduli (E), and apparent toughness moduli (u) were computed. RESULTS: Significant differences in mechanical properties were found between SI and AP directions in both first and second overload tests. Mechanical anisotropy far exceeded differences resulting from overloading the structure in the orthogonal direction. No significant differences were found in mean UFS and mean u for the first or second overload tests. A significant decrease of 35% was identified in mean E for cubes overloaded in the SI direction and then overloaded in the AP direction. CONCLUSIONS: Observed differences in the mechanics of trabecular structure after overload suggests that the trabecular structure has properties that act to minimize loss of apparent toughness, perhaps through energy dissipating sacrificial structures transverse to the primary loading direction.

Structural and remodeling indices in the cancellous bone of the proximal femur across adulthood.

Fragility fractures, including fractures of the femoral neck, result from reductions in the amount, quality and architecture of bone. However, investigations of the underlying structural changes that might predispose to fracture have been largely limited to skeletal sites that do not fracture, such as the iliac crest (IC). The aim of this study was to use histomorphometry to map changes in the architecture and the static remodeling indices of cancellous bone, as a function of age and sex, in bone samples taken from the intertrochanteric (IT) region of the proximal femur at routine autopsy (18-88 years of age). Bone samples for histology were processed from 10-mm cubes of IT cancellous bone. Histomorphometry was performed using an ocular-mounted 10 x 10 graticule at a magnification of x100. An age-dependent decrease in trabecular bone volume was observed in both females and males, as expected (r=-0.75 and r=-0.63, p<0.001, respectively). The underlying mechanisms for bone turnover appeared to be different between males and females. Thus, while the static index of bone resorption (ES/BV) was positively age-dependent in males and females (p<0.001, p<0.03, respectively), the index of bone formation (OS/BV) correlated positively with age in the female group only (p<0.001 vs. NS). Perhaps reflecting an increase in bone formation in older females, the OS/ES ratio was greater in older females than younger females or males. Surprisingly, while resorption indices increased in older males compared with their younger counterparts, bone formation indices increased only in the older female cohort. The IT region in the proximal femur is adjacent to the site commonly involved in fragility fracture. With the limitation that these results describe cross-sectional data, they provide useful insights into changes in the cancellous bone structure and at the bone surface of females and males over the age range of 20-90 years, at a clinically relevant skeletal site.

A MnCl2-based MR signal intensity linear response phantom.

PURPOSE: This study aimed to develop a manganese chloride (MnCl2)-based phantom model that would allow progressive quantitative assessment of tissue hydration based on observed magnetic resonance (MR) imaging signal intensity (SI) linearity characteristics. MATERIALS AND METHODS: The study was performed using a progressive signal refinement technique that allowed development of an imaging tool for semiquantitative sequential discrimination of MR signal responses. A series of 82 phantoms comprising a gelatin-set MnCl2 composite were imaged under basic T1- and T2-weighted conditions. MR SI measurements were taken using region-of-interest selection, and MnCl2 concentrations were adjusted to allow development of a pair of 8-tube phantoms. These phantoms permitted progressive incremental assessment of hydration based on fundamental MR SI response. RESULTS: Statistical analysis showed that phantom MR signal response linearity can be achieved using the phantoms described under both T1 and T2 imaging conditions, yielding R2 values of 0.97 and 0.94, respectively. CONCLUSION: This novel MnCl2-based phantom can be used as a noninvasive reference standard for quantitative classification of in vivo tissue hydration based on routine clinical MR imaging sequences. Progressive correlation testing using a human cartilage sample should be performed to further refine the model for clinical application.

Stability of RNA isolated from human trabecular bone at post-mortem and surgery.

To determine the reliability of gene expression studies in human post-mortem bone, it is important to evaluate the stability of RNA isolated from such tissues as a function of the post-mortem interval. The stability of total RNA and bone-specific mRNA species was examined in bone samples obtained from routine autopsies and at surgery. The optimal temperature for any storage and transport of the bone before RNA isolation was shown to be 4 degrees C, and RT-PCR analysis is the preferred technique for the analysis of gene expression in post-mortem bone as it tolerates partial RNA degradation. For gene expression studies in bone, post-mortem cases, with a post-mortem interval of less than 48 h, should be selected, and the time that bone is stored after retrieval at autopsy or surgery should be kept to a minimum. Overall, our findings indicate that with appropriate storage and handling, RNA can be reliably isolated from human bone obtained at post-mortem and surgery to study ex vivo the pattern of gene expression in healthy individuals and in patients with musculoskeletal diseases such as osteoporosis and osteoarthritis.

Evidence for reduced bone formation surface relative to bone resorption surface in female femoral fragility fracture patients.

Fragility fractures, including neck of femur fractures, result from reductions in the amount, quality and architecture of bone. The aim of this study was to compare the cancellous bone structure, and static indices of bone turnover, in female patients, who had sustained fragility fracture at the femoral neck, with age-matched females without fragility fracture. Bone samples were taken from the intertrochanteric region of the proximal femur of female patients undergoing hip arthroplasty surgery for a subcapital fragility fracture of the femoral neck (#NOF) or from age-matched female control individuals at routine autopsy. Contiguous bone samples were analyzed for undecalcified histomorphometry and for mRNA expression. The histomorphometric data, which were normally distributed, indicated no difference between the mean values for any of the structural parameters in control and fracture samples. In particular, the bone volume (BV/TV) values were not different and did not change significantly with age in these cohorts of individuals aged >65 years. The static indices of bone turnover, eroded surface (ES/BS) and osteoid surface (OS/BS), were positively correlated with age in the >65-year-old control group (p < 0.055 and p < 0.03, respectively). The median values for these indices were not different between the fracture and control groups. However, both the median and the range of OS/BS values were increased for >65-year-old controls compared with a group of younger females aged <65 years, suggesting an increase in bone formation surface in older females in the proximal femur after 65 years of age. When the data were further interrogated, a reduction in the percentage osteoid surface to eroded surface quotient (OS/ES) was found for the fracture group compared with the age-matched control group suggesting a reduced adaptive modeling drift capability in the fracture group. In contiguous bone samples, increased median values for receptor activator of nuclear factor kappa beta (RANK) and interleukin-6 (IL-6) mRNA expression were observed in the fracture group. Study of cultured human osteoblasts showed that recombinant human IL-6 (rhIL-6) inhibited osteoblast differentiation, as measured by an increase in the immature osteoblast marker, STRO-1 and concomitantly decreased expression of the osteoblast maturation marker, alkaline phosphatase. Importantly, cells cultured in the presence of IL-6 showed significantly less mineral deposition in vitro compared with control cultures. These data suggest that perturbations in bone formation surface, relative to resorption surface, are potentially important in producing bone in the proximal femur with increased propensity to fracture.

Antero-postero differences in cortical thickness and cortical porosity of T12 to L5 vertebral bodies.

OBJECTIVE: This study will investigate interrelationships between the cortical shell and cancellous bone trabecular thickness, in vertebral bodies. METHODS: One hundred and sixty vertebral bodies from T12 to L5 were obtained at autopsy. The average age of the cohort was 59.3+/-22.1 years (range = 20-94 years). Cortical thickness, cortical porosity and trabecular thickness from the adjacent cancellous bone were measured. RESULTS: At the mid-vertebral body anterior cortical thickness was significantly greater than posterior cortical thickness (524 +/- 352 vs. 370 +/- 283 microm, respectively, P < 0.0001) and mid-anterior cortical porosity was significantly less than mid-posterior cortical porosity (24 +/- 14% vs. 32 +/- 16%, respectively, P < 0.0001). There were no anterior/posterior differences in trabecular thickness of the cancellous bone adjacent to the cortical walls. CONCLUSION: This study provides a novel perspective of T12 to L5 vertebral body bone, where measurement of cortical thickness and cortical porosity in a cohort of skeletally normal individuals revealed structural differences between load bearing anterior and posterior cortical walls. The data suggest that modulators of change to vertebral body bone may affect the cortical and trabecular bone differently. The relationships between cortical and cancellous bone suggest that the middle sectors of the vertebral body play a critical role in load bearing.

In vivo intrarater and interrater precision of measuring apparent bone mineral density in vertebral subregions using supine lateral dual-energy x-ray absorptiometry.

Analysis of apparent bone mineral density (BMD) in the lumbar spine is commonly based on anteroposterior (AP) scanning using dual-energy X-ray absorptiometry (DXA). Although not widely used, clinically important information can also be derived from lateral scanning. Vertebral bone density, and therefore strength, can may vary in different subregions of the vertebral body. Therefore, subregional BMD measurements might be informative about fracture risk. However, the intrarater and interrater precision of in vivo subregional BMD assessments from lateral DXA remains unknown. Ten normal, young (mean: 24 yr) and 10 older (mean: 63 yr) individuals with low BMD were scanned on one occasion using an AP/lateral sequence. Each lateral scan was reanalyzed six times at L2 by three raters to determine the intrarater and interrater precision in selecting seven regions of interest (subregions). Precision was expressed using percentage coefficients of variation (% CV) and intraclass correlation coefficients (ICC). Intrarater precision ranged from ICC(1,1) 0.971 to 0.996 (% CV: 0.50-3.68) for the young cohort and ICC(1,1) 0.934 to 0.993 (% CV: 1.46-5.30) for the older cohort. Interrater precision ranged from ICC(2,1) 0.804 to 0.915 (% CV: 1.11-2.35) for the young cohort and ICC(2,1) 0.912 to 0.984 (% CV: 1.85-4.32) for the older cohort. Scanning a subgroup of participants twice with repositioning was used to assess short-term in vivo precision. At L2, short-term in vivo precision ranged from ICC(1,1) 0.867 to 0.962 (% CV: 3.38-9.61), at L3 from ICC(1,1) 0.961 to 0.988 (% CV: 2.02-5.57) and using an L2/L3 combination from ICC(1,1) 0.942 to 0.980 (% CV: 2.04-4.61). This study demonstrated moderate to high precision for subregional analysis of apparent BMD in the lumbar spine using lateral DXA in vivo.

Interrelationships between structural parameters of cancellous bone reveal accelerated structural change at low bone volume.

UNLABELLED: This study shows that change to cancellous bone structure is bone volume-dependent in a nonlinear manner. At low bone volume (< 15%), trabecular thickness and trabecular separation change at a much greater rate than at higher bone volume. This suggests that the structural integrity of the cancellous bone may become rapidly compromised when bone volume falls below a critical value. INTRODUCTION: While bone mass is the major determinant of bone strength, this mass-based paradigm does not fully account for the contribution of the bone microstructure to mechanical efficiency. Geometric models of cancellous bone structure have been formulated based on stylized representations of the trabecular elements, where the relationships between bone volume and bone surface of cancellous bone are complex and reflect the modulating effect on the cancellous bone structure of bone remodeling at the trabecular surfaces. Using the plate model of cancellous bone structure, the interrelationships between parameters of cancellous bone structure have been studied. MATERIALS AND METHODS: Two hundred eighty histological sections of human cancellous bone from eight skeletal sites were analyzed. The structural parameters of cancellous bone (BV/TV, BS/TV, BS/BV, Tb.Th, Tb.Sp, Tb.N, and TBPf) were obtained. RESULTS AND CONCLUSIONS: This study shows that change to cancellous bone structure is bone volume-dependent in a nonlinear manner. At low bone volume (< 15%), structural parameters of cancellous bone, such as trabecular thickness and trabecular separation, change at a much greater rate than at higher bone volume. This suggests that the structural integrity of the cancellous bone may become rapidly compromised when bone volume falls below a critical value. These data describe the complex relationships between bone mass and structure in cancellous bone that are often overlooked in the mass-based paradigm of bone strength. Histomorphometric descriptors of cancellous bone structure highlight the potential for accelerated deterioration of the structure with low bone volume, which leads to increased risk of fracture. From a clinical viewpoint, estimation of an individual's fracture risk is constrained to noninvasive techniques, which only provide bone mineral density or bone mineral content. Therefore, there is a need to better correlate measurement of bone mass with measurements of structural parameters.