Bone Microstructure Parameters Research Articles

Serum Estradiol Levels Are Inversely Associated With Cortical Porosity in Older Men

Context:The key role of serum estradiol (E2) for bone health in men is well established. The effect of serum sex steroids on bone microstructure, measured by high-resolution peripheral quantitative computed tomography, remains unknown in elderly men.Objective:The objective of the study was to examine the associations between serum sex steroids and bone microstructural parameters in older men.Methods:Trabecular and cortical bone microstructure at the tibia was measured by high-resolution peripheral quantitative computed tomography in 440 men (mean 80 y of age) participating in the population-based Osteoporotic Fractures in Men Sweden cohort. Serum levels of E2 and T were analyzed with mass spectrometry and free E2 and free T levels were calculated using law-of-mass-action equations.Results:Age-adjusted models demonstrated that E2 and free E2 but not T or free T associated significantly inversely with cortical porosity. The associations between E2 and free E2 and cortical porosity remained significant after further adjustment for height, weight, physical activity, calcium intake, and smoking. Models including both serum E2 and T demonstrated that E2 (standardized β = −.12, P < .05) but not T associated independently with cortical porosity. A similar independent association was found for free E2 (standardized β = −.12, P < .05) but not free T. Free E2 associated significantly with trabecular bone volume fraction in the age-adjusted models, but this association did not remain significant after further adjustment.Conclusions:Serum E2 levels associated inversely with cortical porosity in 80-year-old men. We propose that low serum E2 may reduce cortical bone strength, at least partly, by increasing cortical porosity and thereby increase fracture risk in older men.

Challenges in longitudinal measurements with HR-pQCT: Evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility

Definition of identical regions between repeated computed tomography (CT) scans is a key factor to monitor changes in bone microarchitecture. In longitudinal studies, accurate determination of the volume of interest (VOI), using three dimensional (3D) registration may improve precision. Therefore, the aim of our study was to investigate the short-term reproducibility of bone geometry, density, microstructure and biomechanical parameters assessed by HR-pQCT and micro-finite element (μFE) derived analyses, using the cross-sectional area (CSA) registration method in comparison with the use of 3D registration, to find overlapping regions between scans.Fifteen healthy individuals (aged 21–47years) underwent 3 separate scans at the distal radius and tibia, within a one-month interval. Reproducibility was assessed after double contouring the cortical compartment and after applying three different methods to determine the common region between repeated scans: (i) the VOI was determined with no registration, i.e., on 110 slices, (ii) the VOI was determined after CSA-based registration, and (iii) the VOI was determined after 3D registration.Both pre- and post-registration short-term reproducibility for each subject was determined. With no registration, CVrms of geometry parameters ranged from 0.5 to 3.7%, showing a slight variation in the CSA between scans. When the CSA registration method was employed, the variability of geometry (CVrms<1.8%) and density parameters (CVrms<1.8%), was better than that obtained without registration. By removing the effect of repositioning, the 3D registration further improved the reproducibility of cortical bone measurements compared to other methods. Indeed, significant improvements were found for cortical geometry and microstructure measurements (CVrms ranged from 0.4% to 10.7% at both sites; p<0.05), whereas the impact on trabecular bone measurements was restricted to its geometry parameter. The repositioning error was significantly reduced, most markedly at the radius compared to the tibia.For μFE measures, the impact of 3D registration on whole bone stiffness was negligible, indicating adequate assessment of longitudinal changes in estimated biomechanical properties, even without registration.In conclusion, we have shown that the 3D registration improved the identification of the common region retained for longitudinal analysis, contributing to improve the reproducibility of cortical bone parameter measurements. We also quantified the minimally detectable bone changes to help designing future studies with HR-pQCT.

Inter-individual variability of bone density and morphology distribution in the proximal femur and T12 vertebra

Bone geometry, density and microstructure can vary widely between subjects. Knowledge about this variation in a population is of interest in particular for the design of orthopedic implants and interventions. The goal of this study is to investigate the local variability of bone density and microstructural parameters between subjects using a novel inter-subject image registration approach. Human proximal femora of 29 and T12 vertebrae of 20 individuals were scanned using a HR-pQCT and a micro-CT system, respectively. A pre-defined iso-anatomic mesh template was morphed to each micro-CT scan. For each element bone volume fraction and other morphological parameters (Tb.Th, Tb.N, Tb.Sp, SMI, DA) were determined and assigned to the element. A coefficient of variation (CV) was calculated for each parameter at each element location of the 29 femora and 20 T12 vertebrae. Contour plots of the CV distribution revealed very detailed information about the inter-individual variation in bone density and morphology. It is also shown that analyzing large sub-volumes, as commonly done in previous studies, would miss much of this variation. Detailed quantitative information of bone morphological parameters for each sample in the femur and the T12 database and their inter-individual variability are available from the mesh templates as supplementary data (http://w3.bmt.tue.nl/nl/fe_database/). We expect that these results can help to optimize implants and orthopedic procedures by taking local bone morphological parameter variations into account.

Bone quality evaluation at dental implant site using multislice CT, micro‐CT, and cone beam CT

The first purpose of this study was to analyze the correlation between bone volume fraction (BV/TV) and calibrated radiographic bone density Hounsfield units (HU) in human jaws, derived from micro-CT and multislice computed tomography (MSCT), respectively. The second aim was to assess the accuracy of cone beam computed tomography (CBCT) in evaluating trabecular bone density and microstructure using MSCT and micro-CT, respectively, as reference gold standards. Twenty partially edentulous human mandibular cadavers were scanned by three types of CT modalities: MSCT (Philips, Best, the Netherlands), CBCT (3D Accuitomo 170, J Morita, Kyoto, Japan), and micro-CT (SkyScan 1173, Kontich, Belgium). Image analysis was performed using Amira (v4.1, Visage Imaging Inc., Carlsbad, CA, USA), 3Diagnosis (v5.3.1, 3diemme, Cantu, Italy), Geomagic (studio(®) 2012, Morrisville, NC, USA), and CTAn (v1.11, SkyScan). MSCT, CBCT, and micro-CT scans of each mandible were matched to select the exact region of interest (ROI). MSCT HU, micro-CT BV/TV, and CBCT gray value and bone volume fraction of each ROI were derived. Statistical analysis was performed to assess the correlations between corresponding measurement parameters. Strong correlations were observed between CBCT and MSCT density (r = 0.89) and between CBCT and micro-CT BV/TV measurements (r = 0.82). Excellent correlation was observed between MSCT HU and micro-CT BV/TV (r = 0.91). However, significant differences were found between all comparisons pairs (P < 0.001) except for mean measurement between CBCT BV/TV and micro-CT BV/TV (P = 0.147). An excellent correlation exists between bone volume fraction and bone density as assessed on micro-CT and MSCT, respectively. This suggests that bone density measurements could be used to estimate bone microstructural parameters. A strong correlation also was found between CBCT gray values and BV/TV and their gold standards, suggesting the potential of this modality in bone quality assessment at implant site.

Locally measured microstructural parameters are better associated with vertebral strength than whole bone density

Whole vertebrae areal and volumetric bone mineral density (BMD) measurements are not ideal predictors of vertebral fractures. We introduce a technique which enables quantification of bone microstructural parameters at precisely defined anatomical locations. Results show that local assessment of bone volume fraction at the optimal location can substantially improve the prediction of vertebral strength. Whole vertebrae areal and volumetric BMD measurements are not ideal predictors of vertebral osteoporotic fractures. Recent studies have shown that sampling bone microstructural parameters in smaller regions may permit better predictions. In such studies, however, the sampling location is described only in general anatomical terms. Here, we introduce a technique that enables the quantification of bone volume fraction and microstructural parameters at precisely defined anatomical locations. Specific goals of this study were to investigate at what anatomical location within the vertebrae local bone volume fraction best predicts vertebral-body strength, whether this prediction can be improved by adding microstructural parameters and to explore if this approach could better predict vertebral-body strength than whole bone volume fraction and finite element (FE) analyses. Eighteen T12 vertebrae were scanned in a micro-computed tomography (CT) system and FE meshes were made using a mesh-morphing tool. For each element, bone microstructural parameters were measured and correlated with vertebral compressive strength as measured experimentally. Whole bone volume fraction and FE-predicted vertebral strength were also compared to the experimental measurements. A significant association between local bone volume fraction measured at a specific central region and vertebral-body strength was found that could explain up to 90% of the variation. When including all microstructural parameters in the regression, the predictive value of local measurements could be increased to 98%. Whole bone volume fraction could explain only 64% and FE analyses 76% of the variation in bone strength. A local assessment of volume fraction at the optimal location can substantially improve the prediction of bone strength. Local assessment of other microstructural parameters may further improve this prediction but is not clinically feasible using current technology.

The effect of scan parameters on cone beam CT trabecular bone microstructural measurements of the human mandible

The objective of this study was to investigate the effect of different cone beam CT scan parameters on trabecular bone microstructure measurements. A human mandibular cadaver was scanned using a cone beam CT (3D Accuitomo 170; J.Morita, Kyota, Japan). 20 cone beam CT images were obtained using 5 different fields of view (4×4 cm, 6×6 cm, 8×8 cm, 10×10 cm and 10×5 cm), 2 types of rotation steps (180° and 360°) and 2 scanning resolutions (standard and high). Image analysis software was used to assess the trabecular bone microstructural parameters (number, thickness and spacing). All parameters were measured twice by one trained observer. Intraclass correlation coefficients showed high intraobserver repeatability (intraclass correlation coefficient, 0.95-0.97) in all parameters across all tested scan parameters. Trabecular bone microstructural measurements varied significantly, especially in smaller fields of view (p = 0.001). There was no significant difference in the trabecular parameters when using different resolutions (number, p = 0.988; thickness, p = 0.960; spacing, p = 0.831) and rotation steps (number, p = 1.000; thickness, p = 0.954; spacing, p = 0.759). The scan field of view significantly influences the trabecular bone microstructure measurements. Rotation steps (180° or 360°) and resolution (standard or high) selections are not relevant.

Influence of object location in different FOVs on trabecular bone microstructure measurements of human mandible: a cone beam CT study

The aim of this study was to assess the influence of different object locations in different fields of view (FOVs) of two cone beam CT (CBCT) systems on trabecular bone microstructure measurements of a human mandible. A block of dry human mandible was scanned at five different locations (centre, left, right, anterior and posterior) using five different FOVs of two CBCT systems (NewTom™ 5G; QR Verona, Verona, Italy and Accuitomo 170; Morita, Kyoto, Japan). Image analysis software (CTAn software v. 1.1; SkyScan, Kontich, Belgium) was used to assess the trabecular bone microstructural parameters (thickness, Tb.Th; spacing, Tb.Sp; number, Tb.N; bone volume density, BV/TV). All measurements were taken twice by one trained observer. Tb.Th, Tb.Sp and Tb.N varied significantly across different FOVs in the NewTom 5G (p < 0.001) and the Accuitomo 170 (p < 0.001). For location, a significant difference was observed only when measuring BV/TV (p = 0.03) using the NewTom 5G. The trabecular bone microstructural measurements obtained from CBCT systems are influenced by the size of FOVs. Not all trabecular bone parameters measured using different CBCT systems are affected when varying the object location within the FOVs.

High-Resolution Bone Imaging for Osteoporosis Diagnostics and Therapy Monitoring Using Clinical MDCT and MRI

Osteoporosis is classified as a public health problem due to its increased risk for fragility fractures. Osteoporotic fractures, in particular spine and hip fractures, are associated with a high morbidity and mortality, and generate immense financial cost. The World Health Organisation (WHO) based the diagnosis of osteoporosis on the measurement of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA). However, BMD values of subjects with versus without osteoporotic fractures overlap. Furthermore, it was reported that the anti-fracture effects of drugs could be only partially explained by their effects on BMD. Bone strength reflects the integration of BMD and bone quality. The later can be partly determined by measurements of bone microstructure. Therefore, substantial research efforts have been undertaken to assess bone microstructure by using high-resolution imaging techniques, including high-resolution peripheral quantitative computed tomography (hr-pQCT), high-resolution multi-detector computed tomography (MDCT), and high-resolution magnetic resonance imaging (MRI). Clinical MDCT and MRI systems are broadly available and allow an adequate depiction of the bone microstructure at the clinically most important fracture sites, i.e. radius, spine and hip. Bone microstructure parameters and finite element models can be computed in high-resolution MDCT and MR images. These measurements improved the prediction of bone strength beyond the DXA-derived BMD and revealed pharmacotherapy effects, which are partly not captured by BMD. Therefore, high-resolution bone imaging using clinical MDCT and MRI may be beneficial for osteoporosis diagnostics and allow a highly sensitive monitoring of drug treatment, which plays an important role in the prevention of fragility fractures.

Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats

The aim of this study was to evaluate the effects and explore the mechanism of a local injection of a single dose of simvastatin as a strategy to strengthen target bone. Simvastatin was injected into the femurs (5 or 10 mg) or caudal vertebrae (1 or 2 mg) of ovariectomized rats, with an equal volume of vehicle injected as a control. Bone mineral density (BMD), bone microstructure and strength were evaluated at 1 and 5 months post-injection for the femurs and at 12 days post-injection for the vertebrae. Bone mass, adipocyte numbers and Runx2 expression were also examined using histology and immunohistochemistry. Compared with controls, simvastatin significantly increased BMD, bone volume fraction (BV/TV), improved bone microstructural parameters and bone strength in the femurs at both time points (all P < 0.01). Simvastatin-treated femurs contained fewer adipocytes and a higher Runx2 expression. For the caudal vertebrae, simvastatin significantly improved BV/TV, bone microstructures, and bone strength (all P < 0.01) as compared with controls. In conclusion, local injection of a single dose of simvastatin induces early onset and long-lasting bone augmentation in osteoporotic bone, significantly improving BMD, and bone microstructure and biomechanical strength. Simvastatin induces Runx2 expression, which may function to induce osteogenesis and inhibit adipogenesis as an underlying mechanism to augment bone mass.

Triglyceride metabolism in bone tissue is associated with osteoblast and osteoclast differentiation: a gene expression study

The role of bone marrow adipocytes in bone tissue is not yet understood. Adipocytes express enzymes for metabolism of free fatty acids and adipokines such as adiponectin, which have been shown to exert different effects on bone cells. Our aim was to find out whether triglyceride (TG) metabolism in bone tissue is associated with osteoblast and osteoclast differentiation by gene expression analysis of lipoprotein lipase (LPL), hormone sensitive lipase (HSL), fatty acid synthase (FASN), adiponectin, RUNX2, RANK, RANKL and OPG. Bone tissue was obtained from patients undergoing hip arthroplasty due to osteoporosis (OP) (50) or osteoarthritis (OA) (48) or from healthy autopsy controls (14). Lower bone mineral density and microstructural parameters were observed in OP compared to OA. The FASN expression did not differ between groups suggesting similar de novo lipogenesis. Lower LPL and HSL in OP suggest lower FFA release and uptake in OP bone tissue. Adiponectin expression was lower in OP than in OA and a trend was seen for controls. These results suggest OP bone has lower TG metabolism than OA and normal bone. In OP bone, lower osteoblastogenesis and higher osteoclast formation were observed and correlation analysis suggests adiponectin, LPL and HSL are associated with higher osteoblastogenesis and lower osteoclastogenesis. This study gives insights into TG metabolism in the human bone microenvironment. We conclude that OP bone tissue exhibits lower osteoblastogenesis, higher osteoclastogenesis and lower TG metabolism compared to OA or healthy controls.

Accuracy of trabecular bone microstructural measurement at planned dental implant sites using cone‐beam CT datasets

Cone-beam CT (CBCT) images are infrequently utilized for trabecular bone microstructural measurement due to the system's limited resolution. The aim of this study was to determine the accuracy of CBCT for measuring trabecular bone microstructure in comparison with micro CT (μCT). Twenty-four human mandibular cadavers were scanned using a CBCT system (80 μm) and a μCT system (35 μm). Three bone microstructural parameters trabecular number (Tb.N), thickness (Tb.Th) and separation (Tb.Sp) were assessed using CTAn imaging software. Intraclass correlation coefficients (ICC) showed a high intra-observer reliability (≥ 0.996) in all parameters for both systems. The Pearson correlation coefficients between the measurements of the two systems were for Tb.Th 0.82, for Tb.Sp 0.94 and for Tb.N 0.85 (all P's<0.001). The Bland and Altman plots showed strongest agreement in Tb.N (-0.37 μm) followed by Tb.Th (1.6 μm) and Tb.Sp (8.8 μm). Cone-beam CT datasets can be used to evaluate trabecular bone microstructure at dental implant sites. The accuracy for measuring Tb.N was the best followed by Tb.Th and Tb.Sp.

Multicenter precision of cortical and trabecular bone quality measures assessed by high-resolution peripheral quantitative computed tomography

High-resolution peripheral quantitative computed tomography (HR-pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR-pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition-realistic phantoms constructed from cadaveric radii. Single-center precision was determined by repeat scanning over short-term (<72 hours), intermediate-term (3-5 months), and long-term intervals (28 months). Multicenter precision was determined by imaging the phantoms at nine different HR-pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single-center short-term RMSCVs were <1% for all parameters except cortical thickness (Ct.Th) (1.1%), spatial variability in cortical thickness (Ct.Th.SD) (2.6%), standard deviation of trabecular separation (Tb.Sp.SD) (1.8%), and porosity measures (6% to 8%). Intermediate-term RMSCVs were generally not statistically different from short-term values. Long-term variability was significantly greater for all density measures (0.7% to 2.0%; p < 0.05 versus short-term) and several structure measures: cortical thickness (Ct.Th) (3.4%; p < 0.01 versus short-term), cortical porosity (Ct.Po) (15.4%; p < 0.01 versus short-term), and trabecular thickness (Tb.Th) (2.2%; p < 0.01 versus short-term). Multicenter RMSCVs were also significantly higher than short-term values: 2% to 4% for density and micro-finite element analysis (µFE) measures (p < 0.0001), 2.6% to 5.3% for morphometric measures (p < 0.001), whereas Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multicenter precision errors for HR-pQCT parameters were generally less than 5%. Phantom-based multicenter precision was comparable to previously reported in in vivo single-center precision errors, although this was approximately two to five times worse than ex vivo short-term precision. The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs.

Bone QUS measurement performed under loading condition, a more accuracy ultrasound method for osteoporosis diagnosis

Osteoporosis is a worldwide health problem with enormous social and economic impact. Quantitative ultrasound (QUS) method provides comprehensive information on bone mass, microstructure and mechanical properties of the bone. And the cheap, safe and portable ultrasound equipment is more suitable for public health monitoring. QUS measurement was normally performed on bone specimens without mechanical loading. But human bones are subjected to loading during routine daily activities, and physical loading leads to the changes of bone microstructure and mechanical properties. We hypothesized that bone QUS parameters measured under loading condition differ from those measured without loading because the microstructure of bone was changed when loading subjected to bone. Furthermore, when loading was subjected on bone, the loading-lead microstructure change of osteoporosis bone may larger than that of health bone. By considering the high relationship between bone microstructure and QUS parameters, the QUS parameters of osteoporosis bone may changed larger than that of health bone. So osteoporosis may be detected more effectively by the combination of QUS method and mechanical loading.

On the paradoxical determinations of the lacuno-canalicular permeability of bone

The lacuno-canalicular permeability has been shown to play a key role in the behavior of bone tissue. The aim of this study is, by giving an overview of the determinations of this parameter, to question the paradoxical values provided by theoretical predictions and recent experimental measurements. We propose therefore a Kozeny-like law obtained by a numerical method which relates the permeability to the textural parameters of cortical bone microstructure. Moreover, we suggest possible explanations for this paradox considering the empirical difficulties and possible multiphysical effects.

Prediction of bone strength at the distal tibia by HR-pQCT and DXA

Areal bone mineral density (aBMD) at the distal tibia, measured at the epiphysis (T-EPI) and diaphysis (T-DIA), is predictive for fracture risk. Structural bone parameters evaluated at the distal tibia by high resolution peripheral quantitative computed tomography (HR-pQCT) displayed differences between healthy and fracture patients. With its simple geometry, T-DIA may allow investigating the correlation between bone structural parameter and bone strength. Anatomical tibiae were examined ex vivo by DXA (aBMD) and HR-pQCT (volumetric BMD (vBMD) and bone microstructural parameters). Cortical thickness (CTh) and polar moment of inertia (pMOI) were derived from DXA measurements. Finally, an index combining material (BMD) and mechanical property (polar moment of inertia, pMOI) was defined and analyzed for correlation with torque at failure and stiffness values obtained by biomechanical testing. Areal BMD predicted the vBMD at T-EPI and T-DIA. A high correlation was found between aBMD and microstructural parameters at T-EPIas well as between aBMD and CTh at T-DIA. Finally, at T-DIA both indexes combining BMD and pMOI were strongly and comparably correlated with torque at failure and bone stiffness. Ex vivo, at the distal tibial diaphysis, a novel index combining BMD and pMOI, which can be calculated directly from a single DXA measurement, predicted bone strength and stiffness better than either parameter alone and with an order of magnitude comparable to that of HR-pQCT. Whether this index is suitable for better prediction of fracture risk in vivo deserves further investigation.

Effects of cadmium on bone microstructure and serum tartrate-resistant acid phosphatase 5b in male rats

This study investigated the effects of cadmium on bone microstructure and serum tartrate-resistant acid phosphatase 5b (Tracp 5b) in male rats. Sprague-Dawley male rats were divided into three groups that were given CdCl(2) by subcutaneous injection at doses of 0, 0.1 and 0.5 mg/kg body weight (bw) for 12 weeks, respectively. Before killing at the 12th week, microcomputed tomography scanning was performed on the proximal tibia, and urine samples were collected from all of the rats. All rats were then killed, and their blood was collected for biomarkers assay. Bone tissues were dissected for mineral density determinations and histology. The concentration of cadmium in the blood, urine and bone of rats treated with cadmium were significantly higher than in the control group. The bone mineral density, bone mineral concentrations and bone microstructure index of rats treated with cadmium at 0.5 mg/kg bw were clearly lower than in the control rats. Histological investigation also revealed damage to the bone microstructure caused by cadmium. Tracp 5b concentrations in rats treated with cadmium were dose dependently higher than the control. The concentration of cadmium in blood, urine and bone was significantly correlated with Tracp 5b and bone microstructure parameters. Cadmium was shown to induce bone microstructure damage, especially to trabecular bone. The elevated concentrations of serum Tracp 5b suggest that bone resorption mediated via osteoclasts is an important mechanism for the toxic effects of cadmium on bone.

Dynamic evaluation of an osteoporosis rabbit model induced by ovariectomy and glucocorticoid with MR spectroscopy and micro-CT

Objective To dynamically assess the regular pattern of both bone quantity and bone quality by means of MR spectroscopey and Micro-CT scanning in an osteoporosis rabbit model induced by ovariectomy and glucocorticoid, so as to explore the advantage of combining MRS with Micro-CT. Methods Sixty 8-month-old,mature female New Zealand white rabbits were allocated into three groups. Group B ( n =20 ) underwent bilateral ovariectomy (OVX) and Group C (n =20 ) underwent OVX combining with daily i. m. injections of methylprednisolone sodium succinate (MPS). Group A ( n =20 ) were used as sham controls. Bone marrow fat fraction (FF) and bone microstructure parameters were detected by MR spectroscopy and Micro-CT scanning at 2,4,8, and 10 weeks ( 5 rabbits at each time point every group) after operation in three groups. Results Lumber spine bone marrow FF in Group C was significantly increased over the time course of osteoporosis development with significant difference between Group C and Group A at 4,8,and 10 weeks after operation( all P＜0. 01 ). Bone mineral density(BMD) in Group C at 8 and 10 weeks after OVX was significantly decreased compared with Group A ( P＜0. 0l ). A moderately significant negative correlation between marrow fat content and bone microstructure parameters such as BMD, bone volume fraction, trabecular thickness, connectivity density, and trabecular plate number was found, while FF was positively correlated with structure model index and trabecular spacing( all P＜0. 01 ). Conclusions MRS and MicroCT scanning noninvasively evaluate the bone marrow changes of osteoporosis in the field of pathophysiology and microstructure. Combination of both modalities seems to be valuable in the early, comprehensive assessment of bone quality and bone mass in osteoporosis. Key words: Osteoporosis; Model, rabbit; Magnetic resonance spectroscope ; Micro-CT

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis

Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2 years, in postmenopausal osteoporotic women. Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk. Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers. In the intention-to-treat population (n = 83, age: 64 ± 8 years; lumbar T-score: -2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (-0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (-1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated. Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

Variation of trabecular architecture in proximal femur of postmenopausal women

This investigation of microstructure in the human proximal femur probes the relationship between the parameters of the FRAX index of fracture risk and the parameters of bone microstructure. The specificity of fracture sites at the proximal femur raises the question of whether trabecular parameters are site-specific during post-menopause, before occurrence of fragility fracture. The donated proximal femurs of sixteen post-menopausal women in the sixth and seventh decades of life, free of metabolic pathologies and therapeutic interventions that could have altered the bone tissue, constituted the material of the study. We assessed bone mineral density of the proximal femurs by dual energy X-ray absorptiometry and then sectioned the femurs through the center of the femoral head and along the femoral neck axis. For each proximal femur, morphometry of trabeculae was conducted on the plane of the section divided into conventional regions and sub-regions consistent with the previously identified trabecular families that provide regions of relatively homogeneous microstructure. Mean trabecular width and percent bone area were calculated at such sites. Our findings indicate that each of mean trabecular width and percent bone area vary within each proximal femur independently from each other, with dependence on site. Both trabecular parameters show significant differences between pairs of sites. We speculate that a high FRAX index at the hip corresponds to a reduced percent bone area among sites that gives a more homogeneous and less site-specific quality to the proximal femur. This phenomenon may render the local tissue less able to carry out the expected mechanical function.

Characterization of a rabbit osteoporosis model induced by ovariectomy and glucocorticoid

Background and purpose Experimental models of osteoporosis in rabbits are useful to investigate anabolic agents because rabbits have an active Haversian remodeling and achieve skeletal maturiaty quickly. In this study, an experimental model of osteoporosis in rabbits induced by a combination of ovariectomy and glucocorticoid was characterized to provide a useful model for prevention and therapy of osteoporosis.Methods 32 skeletally mature female rabbits were divided randomly into 4 groups: sham control, bilateral ovariectomy (OVX), 1mg/kg/day methylprednisolone (MP) for 8 weeks, and OVX in combination with MP. All rabbits were killed 10 weeks after surgery. Bone mineral density (BMD) of lumbar spine was measured by dual-energy X-ray absorptiometry at baseline, and at 6 and 10 weeks postoperatively. Bone microarchitecture and mechanical properties of lumbar vertebrae were investigated by high-resolution micro-computed tomography and compression test, respectively, after killing.Results Mean BMD of the OVX+MP group at 10 weeks was reduced by about 36% from baseline (p < 0.001). Bone microarchitecture of lumbar vertebrae in the OVX+MP group indicated osteoporosis-associated deterioration. There was a statistically significant reduction in maximum load, stiffness, and energy absorption capacity of lumbar vertebrae in the OVX+MP group, but not in the OVX group, compared to the sham control. In the MP group, BMD and some microarchitecture parameters such as trabecular thickness and bone volume fraction were reduced. The mechanical properties were not statistically significantly different from those in the sham control group, however, although a negative trend was observed.Interpretation Osteopenia can be induced experimentally in rabbits through a combination of OVX and MP, and can be evaluated by BMD, bone microstructure, and mechanical parameters.