Morphometric texture analysis of spinal trabecular bone structure assessed using orthogonal radiographic projections

The measurement of bone microstructure as well as bone mineral density may improve the estimation of bone strength. Cubic specimens (N = 26, 12 mm X 12 mm X 12 mm) of human cadaver vertebrae were cut along three orthogonal anatomic orientations, i.e., superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). Contact radiographs of the bone cubes along all three orientations were obtained and then digitized by a laser scanner with pixel size of 50 microns x 50 microns. The specimens were tested in compression along the 3 orthogonal orientations and the Young's modulus (YM) was calculated for each direction. Quantitative computed tomography (QCT) was used to obtain a measure of trabecular bone mineral density (BMD). Global gray level thresholding and local thresholding algorithms were used to extract the trabecular bone network. Apparent trabecular bone fraction (ABV/TV), mean intercept length (I.TH), mean intercept separation (I.SP), and number of nodes (N.ND) were measured from the extracted trabecular network. Fractal dimension (Fr.D) of the trabecular bone texture was also measured. Paired t-tests showed that the mean values of each texture parameter (except ABV/TV) and of YM along the SI direction were significantly different (p < 0.05) from those along the ML and AP direction. However, the mean values along the ML and AP directions were not significantly different. Multivariate regression of YM as a function of the texture parameters and BMD showed that without adjusting for the effect of BMD, YM was significantly explained by all the texture parameters (R2 = 0.2-0.6). When BMD was included in the regression, although the variations in YM of ML, AP, and SI orientations could be explained by BMD alone, some of the texture parameters did improve the overall prediction of the biomechanical properties, while, some parameters such as ABV/TV and Fr.D in the ML orientation showed a more significant overall effect in explaining mechanical strength than did BMD. In conclusion, trabecular texture parameters correlated significantly with BMD and YM. Trabecular texture parameters from projectional radiographs reflect the anisotropy of trabecular structure. Quantitative radiographic assessment of trabecular structure using fine-detail radiography can potentially improve the estimation of bone strength.     

In vivo high resolution MRI of the calcaneus: differences in trabecular structure in osteoporosis patients

The purpose of this study was to use high resolution (HR) magnetic resonance (MR) images of the calcaneus to investigate the trabecular structure of patients with and without osteoporotic hip fractures and to compare these techniques with bone mineral density (BMD) in differentiating fracture and nonfracture patients. Axial and sagittal HR MR images of the calcaneus were obtained in 50 female (23 postmenopausal patients with osteoporotic hip fractures and 27 postmenopausal controls). A three-dimensional gradient-echo sequence was used with a slice thickness of 500 micron and in plane resolution of 195 x 195 micron. Texture analysis was performed using morphological features, analogous to standard histomorphometry and fractal dimension. Additionally, BMd measurements of the hip (dual-energy X-ray absorptiometry) were obtained in all patients. Significant differences between both patient groups were obtained using morphological parameters and fractal dimension as well as hip BMD (p < 0.05). Odds ratios for the texture parameters apparent (app.) bone volume/total volume and app. trabecular separation were higher than for hip BMD. Receiver operator characteristic values of texture measures and hip BMD were comparable. In conclusion, trabecular structure measures derived from HR MR images of the calcaneus can differentiate between postmenopausal women with and without osteoporotic hip fractures.     

Immobilisation induced bone loss in the sheep is not modulated by calcitonin treatment

The effect of calcitonin on immobilisation-induced loss of cortical and trabecular bone was studied in adult female sheep. The left calcaneus of 24 adult female Welsh mountain sheep was protected from normal loading by placing an external fixator across the hock joint, from the tibia to the metatarsus. In vivo strain gauge recordings from similar animals showed that this procedure resulted in a 50% reduction in principal strain magnitude in the shaft of the calcaneus during walking. All animals received intramuscular injections three times weekly. Half of the sheep received 100 i.u. of salmon calcitonin while the remainder received vehicle alone. The experiment was conducted blind. Over the 12 week period of the experiment, dual photon absorptiometry was performed at monthly intervals to measure the bone mineral content (BMC) of the calcanei. In all the animals, the loss of bone associated with the functional protection afforded by the fixator was highly significant (p < 0.0001). There was however, no significant difference in either the amount or rate of bone loss between animals which had received calcitonin and those which had not. Post mortem measurement of the cortical thickness of the shaft of the calcaneus revealed a specific pattern of loss which was also not different in the two groups. In this model, calcitonin treatment was ineffective in preventing or retarding loss of bone associated with reduced functional load-bearing over a 12 week period.     

Ultrasonic assessment of bone: a review

In the last 25 years several non-invasive techniques based on the attenuation of ionizing radiation have been developed to quantify bone mineral density in the axial and peripheral skeleton. The use of ultrasounds is another technique which has recently been developed to provide information on the architecture and elasticity of bone. The basic principle of ultrasound measurements is that the speed (SOS = speed of sound) at which ultrasounds propagate in the bone, or the extent of their attenuation (BUA = broad-band ultrasound attenuation) through the bone is determined by bone density and by certain physical properties which are intimately correlated with bone strength. Theoretically, ultrasound bone measurements should provide more information about bone fragility and structure than densitometric techniques. As a result of preliminary studies, several ultrasound devices have been developed by manufacturers. Most of them measure the os calcis which consists almost exclusively of trabecular bone. Measurement precision varies with the instrument used and the site of measurement. The in vitro and in vivo precision for SOS and for BUA are reported in this review. The correlations between ultrasound and bone mineral density measurement suggest that these techniques measure different entities. A significant difference is constantly found between normal and osteoporotic women. Transversal studies have shown a negative correlation between ultrasound measurements and age. Age-related variations are much more significant with BUA than with SOS. Several studies suggest the potential of ultrasound measurements to assess the risk for individuals to develop osteoporosis and its usefulness in treatment follow-up. Further prospective studies are needed to better understand the effectiveness of ultrasounds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elastic wave propagation in bone in vivo: methodology

The purpose of this study was to investigate the usefulness of elastic wave propagation (EWP) in estimating the mechanical properties (elasticity) of human tibia. The test group was composed of 78-yr-old women assigned to high (n = 19) and low (n = 17) bone mineral density (BMD) groups as measured at the calcaneus by the 125I-photon absorption method. The EWP apparatus consisted of an impact-producing hammer with a force strain gauge and two accelerometers positioned on the bone. Results for nylon and acrylic were used to calibrate the apparatus. Polyvinyl chloride (PVC) solid rods and tubes of various diameters were used to evaluate the relationship between the elastic wave velocity and cross-sectional area. The density and the cross-sectional area of tibia were measured by the computerized tomographic (CT) method at the same intersection points as velocity recordings. The velocities in tibia of bending waves produced by the mechanical hammer were found to depend on the density, area moment of inertia, and density-dependent elastic constants of bone. It is important to account for the changes of these quantities along the bone. It is suggested that the velocity of elastic waves and various indices derived there from provide inexpensive ways of evaluating the elastic properties of bone.     

Prediction of vertebral strength in vitro by spinal bone densitometry and calcaneal ultrasound

Spinal bone mineral density (BMD) measurements and calcaneal ultrasound were compared in terms of their ability to predict the strength of the third lumbar vertebral body using specimens from 62 adult cadavers (28 females, 34 males). BMD was measured using dual X-ray absorptiometry (DXA) in both vertebra and calcaneus. Quantitative computed tomography (QCT) was used to determine trabecular BMD, cortical BMD, cortical area, and total cross-sectional area (CSA) of the vertebral body. Bone velocity (BV) and broadband ultrasonic attenuation (BUA) were measured in the right calcaneus. Vertebral strength was determined by uniaxial compressive testing. Vertebral ultimate load was best correlated with DXA-determined vertebral BMD (r2 = 0.64). Of the QCT parameters, the best correlation with strength was obtained using the product of trabecular BMD and CSA (r2 = 0.61). For vertebral ultimate stress, however, the best correlation was observed with QCT-measured trabecular BMD (r2 = 0.51); the correlation with DXA-determined BMD was slightly poorer (r2 = 0.44). Calcaneal ultrasound correlated only weakly with both ultimate load and stress with correlation coefficients (r2) of 0.10-0.17, as did calcaneal BMD (r2 = 0.18). Both spinal DXA and spinal QCT were significantly (p < 0.001) better predictors of L3 ultimate load and stress than were either calcaneal ultrasound or calcaneal DXA. Multiple regression analysis revealed that calcaneal ultrasound did not significantly improve the predictive ability of either DXA or QCT for L3 ultimate load or stress. Calcaneal DXA BMD, bone velocity, and BUA correlated well with each other (r2 = 0.67-0.76), but were only modestly correlated with the DXA and QCT measurements of the vertebra. These data indicate that spinal DXA and spinal QCT provide comparable prediction of vertebral strength, but that a substantial proportion (typically 40%) of the variability in vertebral strength is unaccounted for by BMD measurements. Ultrasonic measurements at the calcaneus are poor predictors of vertebral strength in vitro, and ultrasound does not add predictive information independently of BMD. These findings contrast with emerging clinical data, suggesting that calcaneal ultrasound may be a valuable predictor of vertebral fracture risk in vivo. A possible explanation for this apparent discrepancy between in vivo and in vitro findings could be that current clinical ultrasound measurements at the calcaneus reflect factors that are related to fracture risk but not associated with bone fragility.     

Trabecular bone mineral and calculated structure of human bone specimens scanned by peripheral quantitative computed tomography: relation to biomechanical properties

The relationship of cortical bone mineral density (BMD), and geometry to bone strength has been well documented. In this study, we used peripheral quantitative computerized tomography (pQCT) to acquire trabecular BMD and high-resolution images of trabeculae from specimens to determine their relationship with biomechanical properties. Fifty-eight human cubic trabecular bone specimens, including 26 from the vertebral bodies, were scanned in water and air. Trabecular structure was quantitated using software developed with Advanced Visual Systems interfaced on a Sun/Sparc Workstation. BMD was also obtained using a whole-body computerized tomography scanner (QCT). Nondestructive testing of the specimens was performed to assess their elastic modulus. QCT and pQCT measurements of BMD of specimens in water were strongly correlated (r2 = 0.95, p < 0.0001), with a slope (0.96) statistically not significantly different from 1. Strong correlations were found between pQCT measurements of specimens in water and in air, for BMD (r2 = 0.96, p < 0.0001), and for apparent trabecular structural parameters (r2 = 0.89-0.93, p < 0.0001). Correlations were moderate between BMD and apparent trabecular structural parameters (r2 = 0.37-0.64, p < 0.0001). Precision as coefficient of variation (CV) and standardized coefficient of variation (SCV) for these measurements was < 5%. For the vertebral specimens, the correlation was higher between elastic modulus and BMD (r2 = 0.76,p < 0.0001) than between elastic modulus and apparent trabecular structural parameters (r2 = 0.58-0.72, p < 0.0001), while the addition of apparent trabecular nodes and branches to BMD in a multivariate regression model significantly increased the correlation with the elastic modulus (r2 = 0.86, p < 0.01). Thus, pQCT can comparably and reproducibly measure trabecular bone mineral in water or air, and trabecular structure can be quantitated from pQCT images. The combination of volumetric BMD with trabecular structural parameters rather than either alone improves the prediction of biomechanical properties. Such a noninvasive approach may be useful for the preclinical study of osteoporosis.     

The ability of quantitative ultrasound to predict the mechanical properties of trabecular bone under different strain rates

The ability of quantitative ultrasound to predict the mechanical properties of trabecular bone under different strain rates was investigated. Ultrasound velocity (UV) and broadband attenuation (BUA) were measured for 60 specimens of human trabecular bone. Samples were divided into two equal groups and loaded in compression at the strain rates of 0.0004 and 0.08 s-1. The ultimate strength, elastic modulus, and energy absorption capacity were determined for each specimen. Specimens tested at 0.08 s-1 had a mean value of strength 63% higher than the specimens tested at 0.0004 s-1. The elastic modulus and energy absorption capacity were 82% and 42% higher, respectively, for the higher strain rate. UV and BUA were significantly associated with most mechanical properties at both strain rates. All mechanical properties were also correlated strongly with a linear combination of UV and BUA for both the low and high loading rates. The use of ultrasound parameters may provide good clinical means for assessing the resistance of trabecular bone to both low and high energy trauma.     

A 3D damage model for trabecular bone based on fabric tensors

Motivated by the role of damage in normal and pathological conditions of trabecular bone, a novel 3D constitutive law was developed that describes anisotropic elasticity and the rate-independent degradation in mechanical properties resulting from the growth of cracks or voids in the trabecular tissue. The theoretical model was formulated within the framework of continuum damage mechanics and based on two fabric tensors characterizing the local trabecular morphology. Experimental validation of the model was achieved by uniaxial and torsional testing of waisted bovine trabecular bone specimens. Strong correlations were found between cumulated permanent strain, reduction in elastic moduli and nonlinear postyield stress, which support the hypothesis that these variables reflect the same underlying damage process.     

The effects of smoking on bone mass and the rates of bone loss among elderly Japanese-American men

Bone density and bone loss rates were examined among Japanese-American men categorized as current cigarette smokers, past smokers, and nonsmokers. The design included a retrospective study of smoking and bone density and a prospective study of current smoking and bone loss rates. The mean length of follow-up was 5 years; the setting was the island of Oahu. The subjects included 1303 men in the Hawaii Osteoporosis Study, 51-82 years old at their initial examination. Twenty percent were current smokers, 45% past smokers, and 35% had never smoked. Their bone density was measured at the distal and proximal radius and calcaneus using single photon absorptiometry. Compared with never smokers, current and past smokers had significantly lower bone density, especially in the predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and partially trabecular distal radius (1.8 and 3.3% lower, respectively). The magnitude of the smoking effect was linked strongly to the duration of smoking and also to the number of cigarettes smoked. Bone loss rates subsequent to the initial measurement were greater in the current smokers than the never smokers (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius, respectively) but the differences did not achieve significance. Smokers of more than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never smokers in these same sites; the difference achieved significance at the distal radius. The results from the distal radius suggest that these smokers may increase their fracture risk 10-30% per decade of smoking. The adverse effects of smoking appeared to be greater in cancellous than cortical bone.     

Correlation of total-body bone mineral content determined by dual-energy X-ray absorptiometry with bone mineral density determined by peripheral quantitative computed tomography

RATIONALE AND OBJECTIVES: We sought to determine the value of peripheral quantitative computed tomography (pQCT) in measuring bone mineral density. METHODS: In 50 healthy, eugonodal premenopausal women, we correlated measurements of total bone mineral content (BMCTB), made with dual-energy X-ray absorptiometry (DXA), and bone mineral density, determined by pQCT. RESULTS: The partial correlations, adjusted for weight and age, between BMCTB and cortical bone density, total bone density, and trabecular bone density were .71 (p < .0001), .63 (p < .0001), and .32 (p < .05), respectively. CONCLUSION: These results and the advantages of pQCT--providing precise bone density determinations for trabecular and compact bone separately, having a high spatial resolution that allows a "compartmental" analysis of bone structure, having a low coefficient of variation, and having a minimal radiation dose (< 5 mrem)--confirm the adequacy of using this method for bone mass studies.     

Prediction of vertebral and femoral strength in vitro by bone mineral density measured at different skeletal sites

The aim of the present study was to investigate the prediction of vertebral and femoral strength in vitro by bone mineral density (BMD) measured at different skeletal sites. The third lumbar vertebral body, the right proximal femur, and the right calcaneus were removed from 38 male and 32 female cadavers (mean age 69 years, range 23-92 years). Areal BMD of all bone specimens was determined by dual-energy X-ray absorptiometry (DXA). The failure load of the vertebral body and the femur was determined by mechanical testing. Vertebral and femoral strength were both greater in males than females (p < 0.01), as was BMD at all sites (p < 0.01). Vertebral strength correlated well with vertebral BMD (r2 = 0.64) but was only moderately correlated with BMD measured at the femur (r2 = 0.36) or the calcaneus (r2 = 0.18). Femoral strength showed the highest correlations with femoral BMD (r2 = 0.88) and somewhat weaker relationships with BMD at the vertebra (r2 = 0.50) and the calcaneus (r2 = 0.54). BMD values at the vertebra, femur, and calcaneus were only moderately interrelated (r2 = 0.31-0.65), and vertebral strength correlated only modestly with the strength of the femur (r2 = 0.36). These in vitro results support the concept that optimal prediction of vertebral or femoral strength by DXA requires site-specific assessments.     

Antiretroviral treatment: when to start and with what?

Quantitative ultrasound (QUS) of the calcaneus is a widely utilized method for bone densitometry. However, the meaning of measured parameters, such as speed of sound (SOS) and broadband attenuation (BUA), is not well established. We performed in vitro measurement of dissected human calcaneus (n = 60; male 29, female 31; mean age 81 years) using two QUS machines and also measured bone densities using SXA, DXA and pQCT. Finally, we investigated breaking strength of the calcaneus and studied the correlation with QUS parameters and other assessed parameters. The two QUS measurements were in good agreement in most experiments. SOS correlated most closely with bone mineral densities assessed by pQCT and did not correlate with factors related to bone size, while BUA showed the highest correlation with BMC and association with parameters related with bone size such as bone area and bone width. With maximal breaking stress of the calcaneus, correlations were almost equal among QUS parameters and bone mineral density. We conclude that SOS is the parameter most closely associated with true bone mineral density (g/cm3), whereas BUA represents both bone mineral density and bone size, mimicing BMD assessed by DXA or SXA.     

Characterization of vertebral strength using digital radiographic analysis of bone structure

Bone mineral densitometry (BMD) is useful in predicting fracture risk, but, unfortunately, there is a significant degree of overlap in BMD measurements of patients who have a high risk of fracture and patients with a low risk of fracture. In this study, a method of characterizing trabecular bone structure in digitized radiographs of vertebrae is proposed and assessed. A significant correlation between bone "structure" and the compressive strength of vertebral bodies was found. The utility of the parameter for distinguishing between "weak" and "strong" bone samples was assessed using receiver operating characteristic (ROC) analysis. Using this analysis, the structural parameter produced an area under the ROC of 0.88 +/- 0.05, while a bone density measure produced an area of 0.79 +/- 0.07. The results suggest that the addition of a measure of bone structure to the conventional measures of bone density may prove useful in predicting the quality of bone when considering surgical or medical intervention for osteoporotic conditions.     

Yield strain behavior of trabecular bone

If bone adapts to maintain constant strains and if on-axis yield strains in trabecular bone are independent of apparent density, adaptive remodeling in trabecular bone should maintain a constant safety factor (yield strain/functional strain) during habitual loading. To test the hypothesis that yield strains are indeed independent of density, compressive (n = 22) and tensile (n = 22) yield strains were measured without end-artifacts for low density (0.18 +/- 0.04 g cm(-3)) human vertebral trabecular bone specimens. Loads were applied in the superior-inferior direction along the principal trabecular orientation. These 'on-axis' yield strains were compared to those measured previously for high-density (0.51 +/- 0.06 g cm(-3)) bovine tibial trabecular bone (n = 44). Mean (+/- S.D.) yield strains for the human bone were 0.78 +/- 0.04% in tension and 0.84 +/- 0.06% in compression; corresponding values for the bovine bone were 0.78 +/- 0.04 and 1.09 +/- 0.12%, respectively. Tensile yield strains were independent of the apparent density across the entire density range (human p = 0.40, bovine p = 0.64, pooled p = 0.97). By contrast, compressive yield strains were linearly correlated with apparent density for the human bone (p < 0.001) and the pooled data (p < 0.001), and a suggestive trend existed for the bovine data (p = 0.06). These results refute the hypothesis that on-axis yield strains for trabecular bone are independent of density for compressive loading, although values may appear constant over a narrow density range. On-axis tensile yield strains appear to be independent of both apparent density and anatomic site.     

Differing effects of endogenous and synthetic inhibitors of metalloproteinases on intestinal tumorigenesis

The strength of the radius depends on the mechanical properties of cancellous and cortical bone. By assessing both compartments quantitatively with bone densitometry, we tried to identify the specificity of each in predicting the load at which the distal radius will fracture. Twenty human cadaver forearms were scanned for bone mineral and geometric properties with quantitative computed tomography and dual x-ray absorptiometry. In both a neutral loading situation and one in which the wrist was extended 45 degrees, the load distribution was determined with pressure-sensitive films, and a fracture simulating a fall on the hand was produced with a material testing machine. Fractures that occur with the wrist in extension were produced by a central impact of the scaphoid onto the radiocarpal joint, and those that occur under neutral loading conditions were produced by a more commonly distributed loading pattern. The load at fracture was most specifically predicted (r2=0.74) by bone mineral and geometric measures of the cortex at the shaft of the radius. Bone mineral density measures of trabecular (r2=0.64) and total (r2=0.66) bone were less successful in predicting the fracture load. After adjustment for bone size, the geometric and density measures revealed similar specificity. Cortical bone, therefore, contributes significantly to the strength of the distal radius and may play an important role in the prediction of osteoporotic wrist fractures.     

Comparison of damage accumulation measures in human cortical bone

Elastic modulus degradation, strength reduction, and energy dissipation have traditionally been the properties of choice to monitor the damage process in cortical bone. However, these properties only provide limited insight into the damage process given the complex mechanical nature of bone. In the current study, alternative measures of the damage process were investigated for machined human cortical bone specimens loaded under torsion. Seventy-two bone specimens from 6 human femurs were subjected to a series of torsional relaxation cycles in which damage was induced during a single relaxation cycle and the effects of damage on the elastic, yield, viscous, and failure properties were determined from pre- and post-damage relaxation cycles. The results revealed that degradation of all torsion properties exhibited a significant twist magnitude effect. However, the yield stress and strain, the relaxation rate, and the total relaxation exhibited 5-10 fold greater degradation than both strength and modulus, when residual strength tests were conducted at high shear strain rates. For the loading conditions examined in this study, the results indicated that the relaxation and yield properties of cortical bone are more sensitive to shear damage accumulation and better measures of the damage process than either strength or modulus. Further, the results reveal an important interaction between damage and the viscous behavior of bone which provides new insight into the effects of damage on bone mechanical properties.     

Human vertebral body apparent and hard tissue stiffness

Cancellous bone apparent stiffness and strength are dependent upon material properties at the tissue level and trabecular architecture. Microstructurally accurate, large-scale finite element (LS-FE) models were used to predict the experimental apparent stiffness of human vertebral cancellous bone and to estimate the trabecular hard tissue stiffness. Twenty-eight LS-FE models of cylindrical human vertebral cancellous bone specimens (8 mm in diameter, 9.5 mm in height, one each from twenty-eight individuals) were generated directly from microcomputed tomography images and solved by a special purpose iterative finite element program. The experimental apparent stiffness and strength of the specimens were determined by mechanical testing to failure in the infero superior direction. Morphometric measurements including bone volume fraction (BV/TV), three eigenvalues of the fabric tensor and average P(L) were also calculated. The finite element estimate of apparent stiffness explained much of the variance in both experimental apparent stiffness (r2=0.89) and experimental apparent strength (r2=0.87). Stepwise linear regression analysis demonstrated that the LS-FE estimated apparent stiffness was the only significant predictor of experimental apparent stiffness and strength when it was included with all measured morphometric values. Hard tissue stiffness was quite variable between individuals (mean, 5.7 GPa; S.D. 1.6 GPa), but was not significantly related to age, sex, race, weight or morphometric measures for this sample.     

Alcohol consumption by young actively growing rats: a study of cortical bone histomorphometry and mechanical properties

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease cortical and cancellous bone density, to reduce trabecular bone volume, and to inhibit bone growth at the epiphyseal growth plate. This study addresses the action of alcohol on cortical bone growth using histomorphometric techniques and on mechanical properties by three-point bending. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Femora were removed for analysis after 2, 4, 6, or 8 weeks on the diets. Cortical bone area, bone formation rates, and mineral apposition rates were reduced in the alcohol-fed animals. Bone stiffness, strength, and energy absorbed to fracture were significantly lower in the alcohol-fed animals. This distinctive alcohol effect was revealed to be caused by lower quality bone tissue as reflected by lower elastic moduli and yield strengths.