A study of trabecular bones in ovariectomized goats with micro-computed tomography and peripheral quantitative computed tomography

Osteoporotic fractures occur most frequently in trabeculae-rich skeletal sites. The purpose of this study was to use a high-resolution micro-computed tomography (micro-CT) to investigate the changes in trabecular bone microarchitecture and to use a peripheral quantitative computed tomography (pQCT) to study changes in volumetric bone mineral density (BMD) in a large animal model resulted from ovariectomy (OVX). Ten adult goats were used for this study. The first iliac crest biopsy was harvested before OVX and served as baseline; the second biopsy was collected 6 months later from the opposite side for both pQCT and micro-CT measurements. Results showed that after 6 months of OVX, the BMD of the iliac crest biopsies decreased significantly by 16.3% (P < 0.05). The bone volume density (BV/TV), trabecular number (Tb.N), and connectivity density (Conn.D) measured with micro-CT decrease significantly after OVX, with an average decrease of 8.34%, 8.51%, and 18.52% (P < 0.05 each), respectively. The trabecular plate separation (Tb.Sp) was 8.26% (P < 0.05) greater than baseline after OVX. Significant correlations were found between the reduction of BMD and the decreases of BV/TV and Tb.N (r = 0.839 and 0.719, respectively; P< 0.001 both), as well as the increase of Tb.Sp (r = -0.758, P< 0.001) and SMI (r = -0.697, P< 0.001). In conclusion, this was the first experimental study in goat model to show that OVX-induced bone loss in goats was attributed by deterioration of trabecular microarchitecture.     

Load distribution and the predictive power of morphological indices in the distal radius and tibia by high resolution peripheral quantitative computed tomography

A 3D high resolution peripheral quantitative computed tomography scanner (HR-pQCT) (XtremeCT, Scanco Medical, voxel size 82 microm) has been recently developed that can perform in vivo human measurements on peripheral sites, including the wrist and tibia. The goals of this study were to use HR-pQCT measurements to determine the ability of morphological and density measurements to predict bone apparent stiffness and apparent Young's modulus in the distal radius and tibia, to determine the relative importance of cortical and trabecular bone in carrying load in the human distal radius and tibia. Furthermore, the ability of a sub-volume of trabecular bone apparent Young's modulus to predict the Young's modulus of a whole radius and tibia section was determined. A total of 25 measurements of the radius and 12 measurements of the tibia were used for morphological and finite element analyses of sections, and sub-volume cubes of trabecular bone from the distal radius and tibia. The subjects were chosen to obtain a large variation in age ranges and bone architecture and density. By combining multiple measurements, a strong ability to predict bone apparent stiffness and apparent Young's modulus was found for morphological and density measurements in the radius and tibia (R(2)>0.80). The relative importance of the trabecular and cortical bone in carrying load was also found to vary consistently with location in the sample for both the radius and the tibia. This indicates that measurements of the cortical and trabecular bone are required for assessing fracture risk. A cubic section of trabecular bone was found to be insufficient to accurately represent the apparent bone Young's modulus of a radius or tibia section. Morphological and density measurements of the distal radius and tibia have been shown in this study to predict bone apparent Young's modulus and apparent stiffness, and may indicate when a more time consuming finite element analysis is warranted. It should be noted that these results may be an overestimation of the predictive ability of structural parameters, as the influence of bone density is removed from the finite element analyses, and the results were only influenced by bone structure. A measurement of bone apparent Young's modulus is independent of subject size (as opposed to reaction force), and may provide the ability to distinguish between two patients that have similar mean morphological and density measurements; but different overall structures, and therefore, different fracture risk.     

Assessment of the healing process in distal radius fractures by high resolution peripheral quantitative computed tomography

In clinical practice, fracture healing is evaluated by clinical judgment in combination with conventional radiography. Due to limited resolution, radiographs don't provide detailed information regarding the bone micro-architecture and bone strength. Recently, assessment of in vivo bone density, architectural and mechanical properties at the microscale became possible using high resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (μFEA). So far, such techniques have been used mainly to study intact bone. The aim of this study was to explore whether these techniques can also be used to assess changes in bone density, micro-architecture and bone stiffness during fracture healing. Therefore, the fracture region in eighteen women, aged 50 years or older with a stable distal radius fracture, was scanned using HR-pQCT at 1–2 (baseline), 3–4, 6–8 and 12 weeks post-fracture. At 1–2 and 12 weeks post-fracture the distal radius at the contra-lateral side was also scanned as control. Standard bone density, micro-architectural and geometric parameters were calculated and bone stiffness in compression, torsion and bending was assessed using μFEA. A linear mixed effect model with time post-fracture as fixed effect was used to detect significant (p-value ≤ 0.05) changes from baseline. Wrist pain and function were scored using the patient-rated wrist evaluation (PRWE) questionnaire. Correlations between the bone parameters and the PRWE score were calculated by Spearman's correlation coefficient. At the fracture site, total and trabecular bone density increased by 11% and 20%, respectively, at 6–8 weeks, whereas cortical density was decreased by 4%. Trabecular thickness increased by 23–31% at 6–8 and 12 weeks and the intertrabecular area became blurred, indicating intertrabecular bone formation. Compared to baseline, calculated bone stiffness in compression, torsion and bending was increased by 31% after 12 weeks. A moderate negative correlation was found between the stiffness and the PRWE score. No changes were observed at the contra-lateral side. The results demonstrate that it is feasible to assess clinically relevant and significant longitudinal changes in bone density, micro-architecture and mechanical properties at the fracture region during the healing process of stable distal radius fractures using HR-pQCT.     

Cortical thickness assessed by peripheral quantitative computed tomography: Accuracy evaluated on radius specimens

The purpose of the present study was to evaluate the accuracy of peripheral quantitative computed tomography (pQCT) in measuring the thickness of the radial cortex. Thirty left forearm specimens were scanned on an XCT 960 Stratec pQCT device using a 2.5 mm thick slice at the junction of the middle and the distal third of the radius. Cortical and trabecular areas were assessed using a threshold procedure; cortical thickness was subsequently calculated assuming a circular ring model for the radius. Cortical thickness was also measured on the true shape of bone using an iterative contour detection procedure. Subsequently 2.5 mm thick resin-embedded cylindrical radial specimens, matched with the site of pQCT examination, were obtained and contact radiographs were performed. After tenfold magnification, the cortical and trabecular areas of the specimens were measured using computerized planimetry and cortical thickness was calculated assuming a circular ring model. The cortical thickness could be assessed by pQCT in all cases using the threshold algorithm (mean (SD) 2.51 (0.58) mm) and in 21 cases could be directly measured on the true shape of bone (2.62 (0.32) mm). The cortical thickness of the specimens showed good correlation and high proportionality with that measured using pQCT with either the threshold algorithm (r=0.941, slope=0.976) or the iterative contour detection procedure (r=0.883, slope=0.987). In conclusion, pQCT is able to assess the thickness of the radial cortex, at the junction of the middle and the distal third, with high accuracy.     

Dual-energy X-ray absorptiometry,peripheral quantitative computed tomography,and micro-computed tomography techniques are discordant for bone density and geometry measurements in the guinea pig

This study aims to examine agreement among bone mineral content (BMC) and density (BMD) estimates obtained using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and micro-computed tomography (μCT) against high-resolution μCT and bone ash of the guinea pig femur. Middle-aged (n = 40, 86 weeks) male guinea pigs underwent in vivo followed by ex vivo DXA (Hologic QDR 4500A) scanning for intact and excised femur BMC and areal density. To assess bone architecture and strength, excised femurs were scanned on pQCT (Stratec XCT 2000L) as well as on two μCT scanners (LaTheta LCT-200; Skyscan 1174), followed by three-point bending test. Reproducibility was determined using triplicate scans; and agreement assessed using Bland–Altman plots with reference methods being high-resolution μCT (Skyscan) for BMD and bone ashing for BMC. All techniques showed satisfactory ex vivo precision (CV 0.05–4.3 %). However, bias compared to the reference method was highest (207.5 %) in trabecular bone volume fraction (BV/TV) measured by LaTheta, and unacceptable in most total femur and cortical bone measurements. Volumetric BMD (vBMD) and BV/TV derived by LaTheta and pQCT at the distal metaphysis were biased from the Skyscan by an average of 49.3 and 207.5 %, respectively. Variability of vBMD, BV/TV and cross-sectional area at the diaphysis ranged from ?5.5 to 30.8 %. LaTheta best quantified total femur BMC with an upper bias of 3.3 %. The observed differences among imaging techniques can be attributable to inherent dissimilarity in construction design, calibration, segmentation and scanning resolution used. These bone imaging tools are precise but are not comparable, at least when assessing guinea pig bones.     

Cortical and trabecular bone at the radius and tibia in male and female adolescents with Down syndrome: a peripheral quantitative computed tomography (pQCT) study

Summary

We aimed to describe the structure and strength of the tibia and radius of adolescents with Down syndrome. We observed that despite higher levels of volumetric bone mineral density in determined skeletal sites, they are at higher risk of developing osteoporotic fractures in the future due to their lower bone strength indexes.

Introduction

The aims of the study were to describe the cortical and trabecular volumetric bone mineral density (vBMD), bone mineral content (BMC), area, and bone strength in adolescents with Down syndrome (DS) and to compare them with adolescents without disabilities.

Methods

Thirty adolescents (11 girls) with DS and 28 without disabilities (10 girls) participated in the study. Peripheral quantitative computed tomography measurements were taken at proximal and distal sites of the tibia and radius. Values of total, trabecular, and cortical BMC; vBMD; and area were obtained of each scan. Cortical thickness and endosteal and periosteal circumferences were also measured, and different bone strength indexes were calculated. Student’s t tests were applied between groups.

Results

The DS group showed greater vBMD at distal radius, BMC at proximal radius, and total and cortical vBMD at proximal tibia. The non-DS group showed higher total and trabecular area at the distal radius and total, cortical, and trabecular BMC and area at distal tibia. Higher values of periosteal and endosteal circumference and bone strength were also found in non-DS group.

Conclusions

From these results, it can be believed that even with higher vBMD in determined skeletal sites, adolescents with DS are at higher risk of suffering bone fractures due to an increased fragility by lower resistance to load bending or torsion.     

Cluster analysis of bone microarchitecture from high resolution peripheral quantitative computed tomography demonstrates two separate phenotypes associated with high fracture risk in men and women

Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. “Cluster 1” contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. “Cluster 2” contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p < 0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p < 0.001 for both), and in men, in cluster 2 (p < 0.001) but not 1 (p = 0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone.     

Accuracy and precision of peripheral quantitative computed tomography measurements at the tibial metaphysis.

The ability of 29 peripheral quantitative computed tomography (pQCT) software analysis modes at defining cortical from trabecular bone at three tibial metaphyseal regions was evaluated using five cadaveric tibiae. The accuracy of pQCT was determined by comparing the bone mineral content (BMC) with the ash weight. The precision of the pQCT scanner was calculated using repeated measurements. All the analysis modes had a good accuracy when measuring total bone area and a poor accuracy when measuring cortical bone area at the proximal 5% and distal 4% regions. For trabecular bone measured at all three regions and cortical bone area measured at the proximal 10% region, the Stratec peel mode 5 was the most accurate analysis mode. Highly significant correlations (r = 0.71-0.98) and a moderate accuracy error (coefficient of variation [CV] = 5-22%) was found between ash weight and BMC when using this mode. The precision of bone mineral density (BMD) measurements was good (total, CV = 2-5%; trabecular, CV = 2-5%; cortical, CV = 4-6%). pQCT is a moderately accurate, precise method of measuring trabecular and total BMD at the tibial metaphysis. The authors recommend caution when interpreting results for cortical BMD, as cortical area measurements at the metaphyseal region are less accurate and less precise.     

A 19-week exercise program for people with chronic stroke enhances bone geometry at the tibia: a peripheral quantitative computed tomography study

Background We assessed the impact of a 19-week exercise program on bone health in chronic stroke.Results Those who underwent the program reported significantly more gain in tibial trabecular bone content and cortical bone thickness on the affected side.Conclusion Regular exercise is thus beneficial for enhancing bone health in this population.No commercial party having a direct financial interest in the results of the research supporting this paper has or will confer a benefit upon the author(s) or upon the organization with which the author(s) is/are associated.     

Digital tomosynthesis and high resolution computed tomography as clinical tools for vertebral endplate topography measurements: Comparison with microcomputed tomography

Endplate morphology is understood to play an important role in the mechanical behavior of vertebral bone as well as degenerative processes in spinal tissues; however, the utility of clinical imaging modalities in assessment of the vertebral endplate has been limited. The objective of this study was to evaluate the ability of two clinical imaging modalities (digital tomosynthesis, DTS; high resolution computed tomography, HRCT) to assess endplate topography by correlating the measurements to a microcomputed tomography (μCT) standard. DTS, HRCT, and μCT images of 117 cadaveric thoracolumbar vertebrae (T10–L1; 23 male, 19 female; ages 36–100 years) were segmented, and inferior and superior endplate surface topographical distribution parameters were calculated. Both DTS and HRCT showed statistically significant correlations with μCT approaching a moderate level of correlation at the superior endplate for all measured parameters (R²_Adj = 0.19–0.57), including averages, variability, and higher order statistical moments. Correlation of average depths at the inferior endplate was comparable to the superior case for both DTS and HRCT (R²_Adj = 0.14–0.51), while correlations became weak or nonsignificant for higher moments of the topography distribution. DTS was able to capture variations in the endplate topography to a slightly better extent than HRCT, and taken together with the higher speed and lower radiation cost of DTS than HRCT, DTS appears preferable for endplate measurements.     

Interpretation of whole body dual energy X-ray absorptiometry measures in children: comparison with peripheral quantitative computed tomography

The assessment of bone health in children requires strategies to minimize the confounding effects of bone size on dual energy X-ray absorptiometry (DXA) areal bone mineral density (BMD) results. Cortical bone composes 80% of the total skeletal bone mass. The objective of this study was to develop analytic strategies for the assessment of whole body DXA that describe the biomechanical characteristics of cortical bone across a wide range of body sizes using peripheral quantitative computed tomography (pQCT) measures of cortical geometry, density (mg/mm³), and strength as the gold standard. Whole body DXA (Hologic QDR 4500) and pQCT (Stratec XCT-2000) of the tibia diaphysis were completed in 150 healthy children 6–21 years of age. To assess DXA and pQCT measures relative to age, body size, and bone size, gender-specific regression models were used to establish z scores for DXA bone mineral content (BMC) for age, areal BMD for age, bone area for height, bone area for lean mass, BMC for height, BMC for lean mass, and BMC for bone area; and for pQCT, bone cross-sectional area (CSA) for tibia length and bone strength (stress-strain index, SSI) for tibia length. DXA bone area for height and BMC for height were both strongly and positively associated with pQCT CSA for length and with SSI for length (all P < 0.0001), suggesting that decreases in DXA bone area for height or DXA BMC for height represent narrower bones with less resistance to bending. DXA BMC for age (P < 0.01) and areal BMD (P < 0.05) for age were moderately correlated with strength. Neither DXA bone area for lean mass nor BMC for lean mass correlated with pQCT CSA for length or SSI for length. DXA BMC for bone area was weakly associated with pQCT SSI for length, in females only. Therefore, normalizing whole body DXA bone area for height and BMC for height provided the best measures of bone dimensions and strength. DXA BMC normalized for bone area and lean mass were poor indicators of bone strength.     

Localization of regional forearm bone loss from high resolution computed tomographic images

The precise site of bone loss was evaluated in early postmenopausal women using high resolution computed tomographic (CT) images of forearm measurements. A procedure was devised to quantitate trabecular and subcortical bone density of the distal radius, cortical bone density of the diaphyseal radius, and cortical wall thickness at both measuring sites. Twenty women (mean age 52 years, time since menopause 1 to 4 years) were examined twice at one-year intervals to determine the yearly change of the above mentioned bone parameters. Trabecular bone and subcortical bone showed the same density reduction of 7 mg/cm³ per year. Cortical bone density remains unchanged and no increase in porosity can be seen. For early postmenopausal women the reduction of bone mass (BMC) in the diaphysis of the radius is, therefore, due to a thinning of the cortical wall. This is in accordance with the observed average loss of wall thickness of 0.04 mm per year. The non-invasive determination of the precise localization of bone changes in individual patients should be of value in the assessment of the severity of osteoporosis. Furthermore it has potential in the evaluation of the efficacy of therapeutic procedures in the various disease states.     

A comparison of aortic root measurements by echocardiography and computed tomography

Objectives

The aim of the study is to evaluate an optimal way to assess the dimensions of the aortic root and each of the sinuses of Valsalva and examine how a single measurement in 1 plane (echocardiography or 2-dimensional computed tomography) can underestimate the maximum dimension of the aortic root.

Lean mass and fat mass have differing associations with bone microarchitecture assessed by high resolution peripheral quantitative computed tomography in men and women from the Hertfordshire Cohort Study

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72–81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p < 0.01), cortical thickness (p < 0.05) and trabecular number (p < 0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p < 0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations.     

Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images

There is increasing evidence that, in addition to bone mass, bone microarchitecture and its mechanical load distribution are important factors for the determination of bone strength. Recently, it has been shown that new high-resolution imaging techniques in combination with new modeling algorithms based on the finite element (FE) method can account for these additional factors. Such models thus could provide more relevant information for the estimation of bone failure load. The purpose of the present study was to determine whether results of whole-bone micro-FE (μFE) analyses with models based on three-dimensional peripheral quantitative computer tomography (3D-pQCT) images (isotropic voxel resolution of 165 μm) could predict the failure load of the human radius more accurately than results with dual-energy X-ray absorptiometry (DXA) or bone morphology measurements. For this purpose, μFE models were created using 54 embalmed cadaver arms. It was assumed that bone failure would be initiated if a certain percentage of the bone tissue (varied from 1% to 7%) would be strained beyond the tissue yield strain. The external force that produced this tissue strain was calculated from the FE analyses. These predictions were correlated with results of real compression testing on the same cadaver arms. The results of these compression tests were also correlated with results of DXA and structural measurements of these arms. The compression tests produced Colles-type fractures in the distal 4 cm of the radius. The predicted failure loads calculated from the FE analysis agreed well with those measured in the experiments (R² = 0.75 p < 0.001). Lower correlations were found with bone mass (R² = 0.48, p < 0.001) and bone structural parameters (R² = 0.57 p < 0.001). We conclude that application of the techniques investigated here can lead to a better prediction of the bone failure load for bone in vivo than is possible from DXA measurements, structural parameters, or a combination thereof.     

Pelvic body composition measurements by quantitative computed tomography: association with recent hip fracture

INTRODUCTION: Loss of subcutaneous fat, decreased muscle cross-sectional area (CSA) and increased muscle adiposity are related to declining physical function and disability in the elderly, but there is little information about the relationship of these tissue changes to hip fracture. Thus we have compared body composition measures in women with hip fractures to age-matched controls, using quantitative computed tomography (QCT) imaging of the hip to characterize total adiposity, muscle CSA and muscle attenuation coefficient, a measure of adiposity. MATERIALS AND METHODS: 45 Chinese women (mean age 74.71+/-5.94) with hip fractures were compared to 66 healthy control subjects (mean age 70.70+/-4.66). Hip QCT scans were analyzed to compute total adipose CSA as well as CSA and attenuation values of muscle groups in the CT scan field of view, including hip extensors, abductors, adductors and flexors. The total femur areal BMD (aBMD) was estimated from the QCT images. Logistic regression was employed to compare body composition measures between fracture subjects and controls after adjustment for age, height, BMI and aBMD. Receiver-operator curve (ROC) analyses determined whether combinations of aBMD and body composition had higher area under curve (AUC) than aBMD alone. RESULTS AND CONCLUSIONS: Fracture subjects had lower fat CSA (p<0.0001) than controls but had higher muscle adiposity as indicated by lower attenuation in the adductor, abductor and flexor groups (0.00001相似文献   

Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions.

The International Society for Clinical Densitometry (ISCD) has developed Official Positions for the clinical use of dual-energy X-ray absorptiometry (DXA) and non-DXA technologies. While only DXA can be used for diagnostic classification according to criteria established by the World Health Organization, DXA and some other technologies may predict fracture risk and be used to monitor skeletal changes over time. ISCD task forces reviewed the evidence for clinical applications of non-DXA techniques and presented reports with recommendations at the 2007 ISCD Position Development Conference. Here we present the ISCD Official Positions for quantitative computed tomography (QCT) and peripheral QCT (pQCT), with supporting medical evidence, rationale, controversy, and suggestions for further study. QCT is available for bone mineral density measurements at the spine, hip, forearm, and tibia. The ISCD Official Positions presented here focus on QCT of the spine and pQCT of the forearm. Measurements at the hip may have clinical relevance, as this is an important fracture site; however, due to limited medical evidence, definitive advice on its use in clinical practice cannot be provided until more data emerge.     

The effect of risedronate on bone mineralization as measured by micro-computed tomography with synchrotron radiation: correlation to histomorphometric indices of turnover

The primary goal of our study was to determine changes in bone mineralization in postmenopausal osteoporotic women treated for 3 years with risedronate or placebo. A secondary goal was to determine the relationship between mineralization and indices of bone turnover measured on the same biopsies. The degree of mineralization was measured by micro-computed tomography using Synchrotron radiation (Synchrotron microCT) in the trabecular bone of paired transiliac biopsies taken at baseline and after 3 years of treatment from patients receiving risedronate 5 mg daily (n=11) or placebo (n=8). In the risedronate-treated patients, the average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) at 3 years were significantly increased from baseline by 4.7% (P<0.0001) and 5.4% (P=0.0003), respectively and showed significant negative correlation to turnover indices. In the placebo-treated patients, the increases in Avg-MIN (2.0%) and Peak-MIN (1.6%) were not significantly different from baseline and correlation to turnover indices was weaker. Risedronate significantly reduced the ratio of low- to high-mineralized bone fractions estimated by volume (BMR-V) and surface area (BMR-S) by 70.1% and 54.1%, respectively from baseline. These changes were consistent with the significant reduction of turnover from baseline assessed by reductions in mineralizing surface, MS/BS (-72.8%); activation frequency, Ac.F (-60.4%); and bone formation rate, BFR-BV (-63.6%) in the same biopsies in the risedronate-treated patients. Comparing the pair-wise changes from baseline, risedronate significantly reduced the low-mineralized bone fraction in comparison to placebo, as indicated by a larger reduction of BMR-V (P=0.015) and BMR-S (P=0.035). In the risedronate group, BMR-V and BMR-S showed significant positive correlation to MS/BS (R2: 0.83 and 0.92, respectively). The correlations to Ac.F and BFR-BV were also significant, with BMR-S showing a strong relation (R2: 0.77 and 0.79, respectively). The data suggest that BMR-V and BMR-S are markers of turnover of trabecular bone and may be used to assess treatment effect on turnover in bone biopsies. The results demonstrate that the reduction of turnover by risedronate increased the degree of mineralization and reduced the ratio of low- to high-mineralized bone fractions which may increase bone's resistance to fracture.