Euler<Subscript><Emphasis Type="Italic">strut.cavity</Emphasis></Subscript>, a New Histomorphometric Parameter of Connectivity Reflects Bone Strength and Speed of Sound in Trabecular Bone from Human Os Calcis

The amount of bone and the trabecular microarchitecture are two determinants of bone strength which can be quantified by bone histomorphometry. Among the parameters of bone microarchitecture, the Euler number developed in our laboratory (E _strut.cavity ) and trabecular bone pattern factor (TBPf) evaluate the connectivity and complexity independently of the bone quantity, and the speed of sound (SOS) measured by quantitative ultrasound (QUS) corroborates E _strut.cavity . The aim of the present study was to validate E _strut.cavity , TBPf, and SOS as parameters of bone microarchitecture and their contribution to bone strength. We examined 20 right os calcis taken after necropsy in 11 males and 9 females, aged 52–95 years. At the same anatomic location, we measured SOS and broadband ultrasound attenuation (BUA) using a Hologic Sahara device and bone mineral density (BMD) using a Hologic QDR 1000W. At this site a transcortical cylinder was cut for both apparent density measurement (Ap.Dens) and biomechanical tests (maximum compressive stress (σ_max) and Young’s modulus (E)), and histomorphometry was performed with an automatic image analyzer (Visiolab, Explora Nova, France). E and σ_max were significantly correlated with the parameters of bone quantity, microarchitecture, and QUS. However, after adjustment for the bone quantity, E correlated only with E _strut.cavity , TBPf, and SOS, and σ_max with BUA. In conclusion, the bone connectivity and complexity evaluated by E _strut.cavity and TBPf contribute to bone strength, independently of the bone quantity. The bone mechanical properties may be assessed, in os calcis, in the elastic domain by SOS and in the plastic domain by BUA.     

Does Quantitative Ultrasound of Bone Reflect More Bone Mineral Density Than Bone Microarchitecture?

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus. .Twenty-four specimens, from 12 men and 12 women (mean age 78 ± 10 years; range 53–93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles®, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r² values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rs_p²) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r² values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.     

Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture.

The stability of trabecular bone depends not only on the amount of bone tissue, but also on the three-dimensional orientation and connectedness of trabeculae, which is summarized as trabecular microarchitecture. In previous studies we could demonstrate that in three-dimensional bone tissue the relation of trabecular plates to rods is reflected in the ratio of concave to convex surfaces of the bone pattern in two-dimensional bone sections. For the quantification of the connectedness of these bone patterns we developed a new histomorphometric parameter called Trabecular Bone Pattern factor (TBPf). The basic idea is that the connectedness of structures can be described by the relation of convex to concave surfaces. A lot of concave surfaces represent a well connected spongy lattice, whereas a lot of convex surfaces indicate a badly connected trabecular lattice in two-dimensional sections. By means of an automatic image analysis system we measure trabecular bone area (A1) and perimeter (P1). A second measurement of these two parameters (now A2 and P2) is done after a simulated dilatation of trabeculae on the screen. This dilatation results in a characteristic change of bone area and perimeter depending on the relation of convex to concave surfaces. TBPf is defined as a quotient of the difference of the first and the second measurement: TBPf = (P1 - P2)/(A1 - A2). First measurements of TBPf in 192 iliac crest bone biopsies of autopsy cases show that there is not only age-related loss of bone volume, but also a decrease of trabecular connectedness. By means of TBPf we can demonstrate a significant difference in the age-related loss of trabecular connectivity between male and female individuals.     

Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis.

Long-term treatment with glucocorticoids (GCs) leads to a rapid bone loss and to a greater risk of fractures. To evaluate the specific effects of this treatment on cancellous bone remodeling, structure, and microarchitecture, we compared 22 transiliac biopsy specimens taken in postmenopausal women (65 +/- 6 years) receiving GCs (> or = 7.5 mg/day, for at least 6 months) and 22 biopsy specimens taken in age-matched women with postmenopausal osteoporosis (PMOP), all untreated and having either at least one vertebral fracture or a T score < -2.5 SD. On these biopsy specimens, we measured static and dynamic parameters reflecting trabecular bone formation and resorption. Also, we performed the strut analysis and evaluated the trabecular bone pattern factor (TBPf), Euler number/tissue volume (E/TV), interconnectivity index (ICI), and marrow star volume (MaSV). Glucocorticoid-induced osteoporosis (GIOP), when compared with PMOP, was characterized by lower bone volume (BV/TV), trabecular thickness (Tb.Th), wall thickness (W.Th), osteoid thickness (O.Th), bone formation rate/bone surface (BFR/BS), adjusted mineral apposition rate/bone surface (Aj.AR/BS), and higher ICI and resorption parameters. After adjustment for BV/TV, the W.Th remained significantly lower in GIOP (p < 0.0001). The active formation period [FP(a+)] was not different. Patients with GIOP were divided into two groups: high cumulative dose GCs (HGCs; 23.7 +/- 9.7 g) and low cumulative dose GCs (LGCs; 2.7 +/- 1.2 g). HGC when compared with LGC was characterized by lower W.Th (p < 0.05), BV/TV (p < 0.001), Tb.Th (p < 0.05), trabecular number (Tb.N; p < 0.05), FP(a+)(p < 0.05), and nodes (p < 0.05), and higher E/TV (p < 0.05), ICI (p < 0.005), and TBPf (p < 0.05). When HGC was compared with PMOP, the results were similar except for the MaSV, which was significantly higher (p < 0.005). In summary, GIOP was characterized by lower formation and higher resorption than in PMOP, already present after LGC. With HGCs, these changes were associated with a more dramatic bone loss caused by a major loss of trabecular connectivity.     

Does Quantitative Ultrasound of Bone Reflect More Bone Mineral Density Than Bone Microarchitecture?

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus.Twenty-four specimens, from 12 men and 12 women (mean age 78 +/- 10 years; range 53-93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r(2) values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rsp2) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r(2) values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.     

Fractal Analysis of Bone Texture on Os Calcis Radiographs Compared with Trabecular Microarchitecture Analyzed by Histomorphometry

Microarchitecture of trabecular bone is an important determinant of bone fragility; to date, its evaluation requires bone biopsy with histomorphometry analysis. Methods of noninvasive characterization of trabecular bone microarchitecture are in development and we have developed and validated a bone texture analysis applied to bone radiographs and based on fractal geometry. The aim of our study was to compare this fractal analysis of trabecular bone texture on radiographs to the trabecular microarchitecture analyzed by bone histomorphometry on os calcis biopsies. Thirty eight ossa calcis from 19 human cadavers were studied. Fractal analysis of the trabecular bone of os calcis radiographs was performed by the maximum likelihood estimator following the fractional brownian motion model. The ossa calcis were dissected, then transcortical biopsy cores focused on the fractal analysis region of interest were obtained. Structural and connectivity parameters were measured with both automatic and semiautomatic analyzers. We have found a significant relationship between the fractal Hmean parameter and structural histomorphometric indices; the best correlation was found with trabecular separation (r =−0.55; P= 0.0004). Based on a stepwise regression analysis, trabecular spacing and trabeculae number together would explain 38% of the variance of the fractal parameter. Although the relationship with connectivity indices was poor, our fractal analysis of os calcis trabecular bone texture on radiographs seemed to partially reflect the trabecular bone microarchitecture. Received: 2 July 1997 / Accepted: 8 January 1998     

Variation of ultrasonic parameters with microstructure and material properties of trabecular bone: a 3D model simulation.

This study determined the influence of trabecular bone microstructure and material properties on QUS parameters using numerical simulations coupled with high-resolution synchrotron radiation microCT. INTRODUCTION: Finite-difference time domain (FDTD) simulations coupled to 3D microstructural models of trabecular bone reconstructed from synchrotron radiation microtomography (SR-microCT) were used herein to compare and quantify the effects of bone volume fraction, microstructure, and material properties on QUS parameters. MATERIALS AND METHODS: 3D SR-microCT datasets of 30 trabecular human femoral bone specimens were used to create binary digital 3D models. We studied the sensitivity of quantitative ultrasound (QUS) to bone volume fraction by examining QUS parameters at different stages of trabecular thinning or thickening using an iterative dedicated algorithm. The sensitivity to bone material properties was also assessed by analyzing different scenarios in which density and stiffness could be varied independently. The effect of microstructure was qualitatively assessed by producing virtual bone specimens of identical bone volume fraction. Simulations of ultrasonic wave propagation through the trabecular bone volumes were performed using the FDTD simulation software SimSonic developed by our group. For each structure, both broadband ultrasonic attenuation (BUA) and speed of sound (SOS) were computed. RESULTS: BUA and SOS showed a strong correlation with BV/TV (r(2)=0.94, p<10(-4)) and varied quasi-linearly with BV/TV at an approximate rate of 2 dB/cm.MHz and 11 m/s per percent increase of BV/TV, respectively. Bone alterations caused by variation in BV/TV between 5% and 25% had a greater impact on QUS variables (variation of BUA: 40 dB/cm.MHz; variation of SOS: 200 m/s) than variations caused by alterations of material properties realized either by a 30% change of density or 40% change of stiffness (BUA: 1.7 dB/cm.MHz; SOS: 43 m/s) or than diversity in microarchitecture (BUA:7.8 dB/cm.MHz; SOS: 36 m/s). Moreover, the sensitivity of BUA and SOS to changes in BMD by a given amount realized by a pure change in bone mass (or BV/TV) was found to be predominant over a pure change of mineralization, except for low BV/TV values, where both effects are comparable. CONCLUSIONS: Trabecular bone microstructure (i.e., trabecular thickness) and material properties were changed to quantify the impact of specific determinants on QUS variables. In this sample of unselected autopsies, specimen variability in bone volume seemed to have a somewhat larger impact on QUS variables than the variability of the other determinants assessed. Whether this is also the case for osteoporotic patients remains to be studied.     

Relationships of trabecular bone structure with quantitative ultrasound parameters: in vitro study on human proximal femur using transmission and backscatter measurements

The present study was designed to assess the relationships between QUS parameters and bone density or microarchitecture on samples of human femoral trabecular bone. The normalized slope of the frequency-dependent attenuation (nBUA), the speed of sound (SOS) and the broadband ultrasound backscatter coefficient (BUB) were measured on 37 specimens of pure trabecular bones removed from upper parts of fresh human femurs. Bone mineral density (BMD) was assessed using a clinical scanner. Finally, 8 mm diameter cylindrical cores were extracted from the specimens and their microarchitecture was reconstructed after synchrotron radiation microtomography experiments (isotropic resolution of 10 microm). A large number of microarchitectural parameters were computed, describing morphology, connectivity and geometry of the specimens. BMD correlated with all the microarchitectural parameters and the number of significant correlations was found among the architectural parameters themselves. All QUS parameters were significantly correlated to BMD (R=0.83 for nBUA, R=0.81 for SOS and R=0.69 for BUB) and to microarchitectural parameters (R=-0.79 between nBUA and Tb.Sp, R=-0.81 between SOS and Tb.Sp, R=-0.65 between BUB and BS/BV). Using multivariate model, it was found that microstructural parameters adds 10%, 19%, and 4% to the respective BMD alone contribution for the three variables BUA, SOS and BUB. Moreover, the RMSE was reduced by up to 50% for SOS, by up to 21% for nBUA and up to 11% when adding structural variables to BMD in explaining QUS results. Given the sample, which is not osteoporosis-enriched, the added contribution is quite substantial. The variability of SOS was indeed completely explained by a multivariate model including BMD and independent structural parameters (R(2)=0.94). The inverse problem on the data presented here has been addressed using simple and multiple linear regressions. It was shown that the predictions (in terms of R(2) or RMSE) of microarchitectural parameters was not enhanced when combining 2 or 3 QUS in multiple linear regressions compared to the prediction obtained with one QUS parameter alone. The best model was found for the prediction of Tb.Th() from BUA (R(2)=0.58, RMSE=17 microm). Given the high values of RMSE, these linear models appear of limited clinical value, suggesting that appropriate models have to be derived in order to solve the inverse problem. In this regard, a very interesting multivariate model was found for nBUA and BUB with Tb.Th and Tb.N, in agreement with single scattering theories by random medium. However, the source of residual variability of nBUA and BUB (15% and 45% respectively) remained unexplained.     

Assessment of proximal femur microarchitecture using ultra-high field MRI at 7 Tesla

PurposeThe purpose of this study was to investigate bone microarchitecture of cadaveric proximal femurs using ultra-high field (UHF) 7-Tesla magnetic resonance imaging (MRI) and to compare the corresponding metrics with failure load assessed during mechanical compression test and areal bone mineral density (ABMD) measured using dual-energy X-ray absorptiometry.Materials and methodsABMD of ten proximal femurs from five cadavers (5 women; mean age = 86.2 ± 3.8 (SD) years; range: 82.5–90 years) were investigated using dual-energy X-ray absorptiometry and the bone volume fraction, trabecular thickness, trabecular spacing, fractal dimension, Euler characteristics, connectivity density and degree of anisotropy of each femur was quantified using UHF MRI. The whole set of specimens underwent mechanical compression tests to failure. The inter-rater reliability of microarchitecture characterization was assessed with the intraclass correlation coefficient (ICC). Associations were searched using correlation tests and multiple regression analysis.ResultsThe inter-rater reliability for bone microarchitecture parameters measurement was good with ICC ranging from 0.80 and 0.91. ABMD and the whole set of microarchitecture metrics but connectivity density significantly correlated with failure load. Microarchitecture metrics correlated to each other but did not correlate with ABMD. Multiple regression analysis disclosed that the combination of microarchitecture metrics and ABMD improved the association with failure load.ConclusionFemur bone microarchitecture metrics quantified using UHF MRI significantly correlated with biomechanical parameters. The multimodal assessment of ABMD and trabecular bone microarchitecture using UHF MRI provides more information about fracture risk of femoral bone and might be of interest for future investigations of patients with undetected osteoporosis.     

Association of dietary and biochemical measures of vitamin K with quantitative ultrasound of the heel in men and women

Introduction Low vitamin K nutritional status is associated with increased fracture risk but is inconsistently related to bone mineral density (BMD), suggesting that vitamin K may affect components of bone strength not measured by BMD, such as microarchitecture. Quantitative ultrasound (QUS) may assess trabecular orientation, providing information on the mechanical properties of bone and may serve as a potential alternative to BMD for gaining insight to the relation between vitamin K and bone strength. We therefore examined the association of vitamin K nutritional status measured in several different ways with QUS in men and women who participated in the Framingham Osteoporosis Study. Methods From 1996 to 2001, broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus (heel) were measured in 583 men and 768 women (mean age 59 years). Vitamin K nutritional status was assessed between 1995 and 1998 by three separate measures: plasma phylloquinone concentration, serum percent undercarboxylated osteocalcin (%ucOC) and dietary vitamin K intake. Multiple linear regression analyses were used to calculate regression coefficients in order to evaluate the associations between both measures of QUS and each measure of vitamin K nutritional status. Regression analyses were conducted separately for subgroups of participants defined by gender, menopause status and current use of estrogen replacement medication. Results Among the men, plasma phylloquinone concentration was positively associated with both BUA (P<0.01) and SOS (P=0.02) of the heel. Neither serum %ucOC nor dietary vitamin K intake, however, was associated with QUS measures. Among women, none of the three measures of vitamin K nutritional status were associated with either BUA or SOS, regardless of menopause status or use of estrogen. Although QUS is associated with vitamin K nutritional status in men, the observed relation was not consistent among subgroups of participants. Conclusion These findings suggest that QUS may not be the best method for elucidating the role of vitamin K on the skeleton. From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine, Framingham, Massachusetts, USA.     

Architecture and distribution of cancellous bone yield vertebral fracture clues

The objective of this study was to analyze the structure of cancellous bone and its significance for vertebral fractures. Therefore, the complete spinal column from 40 autopsy cases (18 without diseases affecting the skeleton and 12 osteoporotic) was removed and sectioned in the sagittal plane to a thickness of 1 mm. A surface-stained block grinding technique allowed combined two- and three-dimensional histomorphometric analysis, which included an evaluation of the trabecular bone volume (BV/TV in %) and the trabecular interconnection (TBPf, in mm). In addition, qualitative investigation of the structure of trabecular bone was done. The distribution of trabecular bone volume within the spinal column of a normal skeleton shows a curve, with the highest values in the cervical spine and a decline in the thoracic and lumbar spine. Osteoporosis presents itself with a pathologically diminished trabecular bone volume, whereas the distribution within the spine is comparable to that of the controls. Osteoporotic patients show an apparently reduced trabecular interconnection. It is important that the measured values for TBPf are not only in general higher, but also more widely dispersed. The age-related decrease of trabecular bone mass is due to the transformation from plates to rods. This is quantitatively indicated by the close correlation of BV/TV and TBPf (P < 0.001, r = 0.85). The bone loss in osteoporosis is a loss of structure and a loss of whole trabeculae, which is caused by perforations. It involves a gradual change from normal bone. However, the polyostic heterogenity in osteoporosis is immense. These structural differences demonstrate the development of regions of least resistance within the spine, serving as an explanation of osteoporotic fractures. Due to the polyostotic heterogeneity it is impossible to define a threshold mineral content for crash fractures by diagnostic measurements at any reference site.     

Measurement of human trabecular bone by novel ultrasonic bone densitometry based on fast and slow waves

Summary  Two longitudinal transmitted waves, fast and slow waves, were observed by employing a new quantitative ultrasound (QUS) method. The trabecular bone measurements generated by this method reflect three-dimensional structural information, and the new QUS parameters were able to identify vertebral fractures. Introduction  The aims were to identify new quantitative ultrasound (QUS) parameters that based on new QUS method reflecting not only bone volume but also the microstructures of trabecular bone ex vivo and to observe how much they predict fracture risk in vivo. Methods   Ex vivo measurement: Three human femoral heads were used for the experiment. Attenuation of the slow wave, attenuation of the fast wave, speed of the slow wave, speed of the fast wave (SOFW), bone mass density of trabecular bone, and elastic modulus of the trabecular bone (EMTb) of each specimen were obtained using a new QUS method and compared with three-dimensional structural parameters measured by micro-computed tomography. In vivo measurement: Eighty-nine volunteers were enrolled, and the bone status in the distal radius was measured using a new QUS method. These parameters were compared with data evaluated by peripheral quantitative computed tomography and dual X-ray absorptiometry. Results   Ex vivo measurement: SOFW and EMTb showed correlations with the parameter of trabecular anisotropy. In vivo measurement: The new QUS parameters were able to identify vertebral fractures. Conclusion  The newly developed QUS technique reflects the three-dimensional structure and is a promising method to evaluate fracture risk.     

中老年骨折妇女超声骨质测量中参数分析

目的　用定量超声骨质测量仪对中老年妇女骨折病人检测 ,探讨其参数的意义 ,为骨质疏松性骨折的诊断、防治提供科学依据。方法　用法国DMS公司UBIS 50 0 0型超声骨密度 /骨质量测量仪测量 74例 41岁以上中老年妇女骨折病人的骨质 ,并与 2 1 8例同龄健康妇女作对照。结果　 61岁以前 2组宽波段超声衰减平均值 (BUA)比较差异无显著意义 (P >0 0 5)、而 61岁以后则有显著意义 (P <0 0 1 ) ;51岁以前 2组超声传播速度 (SOS)值比较差异无显著意义 (P >0 0 5)、而 51岁以后则有显著意义 (P <0 0 1 ) ;在绝经后早期 (51～ 60岁 ) 2组比较 ,BUA值差异无显著意义 (P >0 0 5)而SOS值则已有显著意义 (P <0 0 1 )。结论　定量超声骨质测量仪不仅可以提供骨量的指标 ,而且可以对骨结构进行评估 ,无辐射、成本低廉、操作方便 ,在骨质疏松性骨折的早期预测、早期诊断和及时防治中具有重要意义     

Three quantitative ultrasound parameters reflect bone structure

We investigated whether quantitative ultrasound (QUS) parameters are associated with bone structure. In an in vitro study on 20 cubes of trabecular bone, we measured broadband ultrasound attenuation (BUA) and two newly defined parameters—ultrasound velocity through bone (UVB) and ultrasound attenuation in bone (UAB). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) and bone structure was assessed by microcomputed tomography (CT) with approximately 80 m spatial resolution. We found all three QUS parameters to be significantly associated with bone structure independently of BMD. UVB was largely influenced by trabecular separation, UAB by connectivity, and BUA by a combination of both. For a one standard deviation (SD) increase in UVB, a decrease in trabecular separation of 1.2 SD was required compared with a 1.4 SD increase in BMD for the same effect. A 1.0 SD increase in UAB required a reduction in connectivity of 1.4 SD. Multivariate models of QUS versus BMD combined with bone structure parameters showed squared correlation coefficients of r²=0.70–0.85 for UVB, r²=0.27–0.56 for UAB, and r²=0.30–0.68 for BUA compared with r²=0.18–0.58 for UVB, r²<0.26 for UAB and r²<0.13 for BUA for models including BMD alone. QUS thus reflects bone structure, and a combined analysis of QUS and BMD will allow for a more comprehensive assessment of skeletal status than either method alone.     

Clinical and experimental studies of quantitative ultrasound measurement in the os calcis: Prevalence and incidence of vertebral fracture

We performed quantitative ultrasound (QUS) measurements in the os calcis in 3212 women, and evaluated the clinical usefulness of QUS parameters; in particular, their association with vertebral fracture. An experimental study was performed to determine QUS parameters in the os calcis of amputated lower extremities. Broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness showed significant decreases in the groups aged 50–54 years and 55–59 years in healthy women. Diagnostic sensitivity, evaluated by receiver operating characteristic (ROC) analysis, of the QUS parameters to evaluate the prevalence of vertebral fracture was greater than the sensitivity of bone mineral density (BMD) measurement. The incidence of vertebral fracture and the rate of change in QUS parameters after 1 year showed a higher rate of decrease in BUA in women who developed new vertebral fractures. In the experimental study, the BUA differed between two specimens that differed in trabecular architecture and was markedly correlated with maximum load and stiffness. SOS did not differ between the two specimens. These findings indicated that QUS parameters could sensitively reflect trabecular bone fragility during the para-menopausal period. BUA may be useful for evaluating the risk of, vertebral fracture and may be affected by trabecular architecture.     

Bone structure of the calcaneus: analysis with magnetic resonance imaging and correlation with histomorphometric study

The purpose of this study was to compare structural measurements obtained from MR images of the calcaneus with those obtained from conventional histomorphometry. Sagittal magnetic resonance (MR) images of the calcaneus of 24 fresh human cadaveric feet were obtained at a spatial resolution achievable in vivo. A three-dimensional gradient echo-sequence was used with a slice thickness of 700 m and in plane resolution of 172×172 m. Structural analysis (four histomorphometric parameters; seven connectivity parameters) was performed in the superior region of the calcaneus. Bone biopsy specimens were obtained in the same area and were sectioned for histomorphometric study. Most of the MR histomorphometric parameters were overestimated (by a factor ranging from 0.8 to 3), as compared with histomorphometry. However, significant (P<0.05) correlations were found between MR imaging and histomorphometric measurements for bone volume/tissue volume, trabecular separation, trabecular number, star volume of the marrow space, node count and terminus count. MR histomorphometric parameters correlated much better with histomorphometry than connectivity parameters. This study suggests that structural parameters characterizing cancellous bone in the calcaneus can be derived from MR images in the limited spatial resolution regime applicable in vivo.     

Oral Ibandronate Preserves Trabecular Microarchitecture: Micro-Computed Tomography Findings From the Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe Study

Micro-computed tomography (micro-CT) is a quantitative 3-dimensional (3D) scanning procedure used to assess trabecular architecture. In the 3-yr oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe (BONE) study, it was found that oral ibandronate administered daily (2.5 mg) or intermittently (20 mg) significantly reduced vertebral fracture risk by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, vs placebo. Two-dimensional histomorphometric analysis of BONE study biopsies indicated that newly formed bone was of normal quality. In the current analysis, micro-CT was used to assess 3D trabecular microarchitecture. Rod and plate distribution was quantified by differential analysis of the triangulated bone surface. Biopsies were obtained from 110 patients, with 84 evaluable by micro-CT. Median structural model index (SMI; a lower SMI indicates an increased ratio of plates to rods and thus, improved trabecular microarchitecture) was 1.001 with ibandronate vs 1.365 with placebo (90% confidence interval [CI] for difference in medians: –0.626, –0.033), and connectivity density was higher in ibandronate-treated patients (median: 3.904 vs 3.112/mm³, 90% CI for difference in medians: 0.159, 1.517). This indicates that trabecular microarchitecture was better preserved in patients receiving ibandronate than placebo. Taken together with previous results from BONE, these findings indicate that ibandronate treatment preserves bone strength by maintaining good quality trabecular microarchitecture in women with postmenopausal osteoporosis.     

Effect of trabecular bone contour on ultimate strength of lumbar vertebra after bilateral ovariectomy in rats

To test the hypothesis that the effect of trabecular microarchitecture on bone strength varies with the duration of estrogen loss, we evaluated the relationship between three-dimensional (3D) parameters for trabecular microarchitecture and bone minerals with the compressive load of the lumbar vertebra in rats. Female Sprague-Dawley rats (n = 190) were divided into 19 groups. Ten rats were killed at day 0. Half of the remaining rats underwent bilateral ovariectomy (ovx), and the others were subjected to sham surgery. Ten rats from each group were killed at 3, 7, 11, 14, 28, 42, 56, 70, and 84 days postsurgery. Urinary deoxypyridinoline and serum osteocalcin increased significantly in the ovx group from days 28 and 11, respectively, compared with the sham group. Bone mineral content (BMC) and bone mineral density (BMD) of the fifth lumbar body diminished from days 42 and 84, respectively, compared with the sham group. In ovx rats, trabecular bone volume (BV/TV), measured using 3D images of microcomputed tomography, diminished from day 28 compared with both baseline control and sham. The trabecular bone pattern factor (TBPf) and structure model index (SMI) increased from day 28 in the ovx group compared with both baseline control and sham. Ultimate compression loads diminished at day 28 compared with baseline control and decreased progressively thereafter. Neither of these parameters changed in the sham group during the same period. Within 4 weeks post-ovx, TBPf, SMI, and BV/TV correlated with load (p < 0.01). BMC and BMD correlated with load from 6 weeks post-ovx (p < 0.01). Stepwise regression analysis showed that TBPf was the most significant determinant of load within 4 weeks post-ovx (coefficient of determination [R²] = 0.669; p < 0.01). SMI correlated with TBPf (R² = 0.968; p < 0.01). Moreover, R² for ultimate load indicated higher values of 0.975 with TBPf and SMI. However, BMC was the most significant determinant of load from 6 weeks post-ovx (R² = 0.511; p < 0.01), as it was in the sham group. These data suggest that changes in trabecular bone contour with increased bone turnover are critical for reducing lumbar bone strength during the early post-ovx period in rats.