Peripheral quantitative computed tomography of the proximal radius in young subjects--new reference data and interpretation of results

The aim of this contribution is to provide reference data for peripheral quantitative computed tomography (Stratec XCT2000) performed at the proximal radius (the so-called '65% site') of young subjects and to discuss the interpretation of such analyses. Data from a previous reference data study on 469 subjects between 6 and 40 years were re-analyzed and smooth curves were fitted. The corresponding equations allow for calculation of age-, height- and sex-specific z-scores of total cross-sectional area, cortical cross-sectional area, bone mineral content, cortical bone mineral density, total bone mineral density, Strength-Strain Index, muscle cross-sectional area and the ratio between bone mineral content and muscle cross-sectional area. These data should facilitate the clinical use of peripheral quantitative computed tomography in young subjects.     

Critical ages and stages of puberty in the accumulation of spinal and femoral bone mass: the validity of bone mass measurements

In growing children, lumbar and femoral areal bone mineral density (aBMD), as measured by dual-energy X-ray absorptiometry (DXA), is influenced by skeletal growth and bone size. Correction of lumbar bone mineral density (BMD) for bone volume (volumetric BMD [vBMD]), by the use of mathematical extrapolations, reduces the confounding effect of bone size, but vBMD remains dependent on age and bone size during growth. Femoral (neck and mid-shaft) vBMD, assessed by DXA, is independent of age prior to puberty, but a slight increase occurs in late puberty and after menarche. Femoral (mid-shaft) cortical bone density and radial cortical and trabecular bone densities, assessed by quantitative computed tomography (QCT), show no peak during childhood or adolescence. Bone strength index, calculated by peripheral QCT, increases with age and correlates with handgrip strength, bone cross-sectional area and cortical area. Puberty is one of the main factors that influences lumbar bone mineral content and aBMD accumulation, but a high incidence of fractures occurs during this period of life, which may be associated with a reduced aBMD.     

Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.

Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD.     

Effects of physical training on cortical bone at midtibia assessed by peripheral QCT.

Effects of long-term exercise on volumetric bone mineral density (vBMD), bone mineral content, bone geometric properties, and the strength indexes of bone were examined in a cross-sectional study of athletes and controls. Tibias of 25 jumpers (13 women), 30 swimmers (15 women), and 25 controls (15 women), aged 18-23 yr, were scanned at midsite by using peripheral quantitative computed tomography. The cortical vBMD of female athletes was lower than that of the controls (2.00 +/- 0.05, 1.90 +/- 0.08, and 1.92 +/- 0.12 g/cm3, respectively, for controls, swimmers, and jumpers). On the other hand, periosteal areas of male jumpers and female athletes were greater than that of controls (460 +/- 50, 483 +/- 46, and 512 +/- 55 mm2, respectively, for male controls, swimmers, and jumpers, and 283 +/- 52, 341 +/- 73, and 378 +/- 75 mm2, respectively, for female controls, swimmers, and jumpers). The endocortical area of female swimmers was greater than that of controls (103 +/- 29, 148 +/- 52, and 135 +/- 54 mm2, respectively, for controls, swimmers, and jumpers). The polar moment of inertia and strength strain index of male jumpers and female athletes were significantly greater than those of controls, except for the difference in strength strain index between male jumpers and controls. We conclude that the improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation and not to vBMD.     

Peripheral quantitative computed tomography at the distal radius: cross-calibration between two scanners

Peripheral quantitative computed tomography (pQCT) is an important technique to study the interaction between the muscle and bone systems. We have recently established pQCT reference ranges for children, adolescents and young adults using a recent version (XCT 2000) of the Stratec scanners (Stratec Inc., Pforzheim, Germany). However, the previous version of this type of scanner (XCT 900) is still widely used and cross-calibration is needed to use these reference data. Therefore, both distal radii of 19 healthy subjects (age 21 to 59 years; 11 women) were analyzed at the "4% site" using both the XCT 900 and the XCT 2000. Cross-sectional area, total and trabecular bone mineral density (BMD), total bone mineral content (BMC) and polar Strength-Strain Index (SSI) results from the two scanners were compared using linear regression analysis. To achieve scanner calibration we used the intercept and slope of the correlations. The correlation coefficients between the two devices were 0.82 for the cross-sectional area, 0.81 for total BMD, 0.97 for trabecular BMD, 0.99 for total BMC and 0.86 for polar SSI. In conclusion, these data allow for the conversion of XCT 900 results at the distal radius to XCT 2000 values and vice versa.     

Bone anabolic effects of parathyroid hormone are blunted by deletion of the Wnt antagonist secreted frizzled-related protein-1

Secreted frizzled-related protein (sFRP)-1 is a Wnt antagonist that when deleted in mice leads to increased trabecular bone formation in adult animals after 13 weeks of age. Treatment of mice with parathyroid hormone (PTH) also increases trabecular bone formation, and some of the anabolic actions of this hormone may result from altered expression of Wnt pathway components. To test this hypothesis, we treated +/+ and -/- female sFRP-1 mice with PTH 1-34 for 30 days and measured distal femur trabecular bone parameters by peripheral quantitative computed tomography (pQCT) and high-resolution micro-computed tomography. During the course of the 32-week study, volumetric bone mineral density (vBMD) declined 41% in vehicle-treated +/+ mice, but increased 24% in vehicle-treated -/- animals. At 8 weeks of age when vBMD was not altered by deletion of sFRP-1, treatment of +/+ and -/- mice with PTH increased vBMD by 147 and 163%, respectively. In contrast, at 24 weeks of age when vBMD was 75% higher in -/- mice than in +/+ controls, treatment with PTH increased vBMD 164% in +/+ animals, but only 58% in -/- mice. Furthermore, at 36 weeks of age when vBMD was 117% higher in -/- mice than in +/+ controls, treatment with PTH increased vBMD 74% in +/+ animals, while no increase was observed in -/- mice. At each of these time points, PTH treatment increased vBMD to a similar level in +/+ and -/- mice, and this level declined with age. In addition, at 36 weeks of age, the vBMD level reached by PTH treatment of +/+ mice was the same as that achieved solely by deletion of sFRP-1. These results indicate that loss of sFRP-1 and PTH treatment increase vBMD to a similar extent. Moreover, as the effects of sFRP-1 deletion on vBMD increase, the ability of PTH to enhance vBMD declines suggesting that there are overlapping mechanisms of action.     

Brief communication: Two and three-dimensional analysis of bone mass and microstructure in a bog body from the Iron Age

Human remains from peat bogs, called "bog bodies," have yielded valuable insights into human history because of their excellent preservation of soft tissue. On the other hand, the acidic environment of the peat leads to an extensive demineralization of skeletal elements, complicating their analysis. We studied the skeleton of the bog body "Moora" dated to approximately 650 B.C. Nondestructive evaluation of the bone was made using contact X-rays, peripheral quantitative computed tomography (pQCT) analysis, multislice computed tomography (CT) and high resolution micro computed tomography (microCT) imaging. Two thousand seven hundred years in the acidic environment of the bog led to a loss of 92.7% of bone mineral density. Despite this demineralization and in contrast to other bog bodies, the spatial structure of the bones of "Moora" is exceptionally well preserved. We found Harris lines and were able to obtain the first three-dimensional data on the trabecular microstructure of the bone of a young woman from the early Iron Age.     

Muscle mass during childhood--relationship to skeletal development

Bone densitometric data often are difficult to interpret in children and adolescents because of large inter- and intraindividual variations in bone size. Here, we propose a functional approach to bone densitometry that addresses two questions: Is bone strength normally adapted to the largest physiological loads, that is, muscle force? Is muscle force adequate for body size? To implement this approach, forearm muscle cross-sectional area (CSA) and bone mineral content (BMC) of the radial diaphysis were measured in 349 healthy subjects from 6 to 19 years of age (183 girls), using peripheral quantitative computed tomography (pQCT). This functional approach to pediatric bone densitometric data should be adaptable to a variety of densitometric techniques.     

Determination of mechanical stiffness of bone by pQCT measurements: correlation with non-destructive mechanical four-point bending test data

Mechanical tests of bone provide valuable information about material and structural properties important for understanding bone pathology in both clinical and research settings, but no previous studies have produced applicable non-invasive, quantitative estimates of bending stiffness. The goal of this study was to evaluate the effectiveness of using peripheral quantitative computed tomography (pQCT) data to accurately compute the bending stiffness of bone. Normal rabbit humeri (N=8) were scanned at their mid-diaphyses using pQCT. The average bone mineral densities and the cross-sectional moments of inertia were computed from the pQCT cross-sections. Bending stiffness was determined as a function of the elastic modulus of compact bone (based on the local bone mineral density), cross-sectional moment of inertia, and simulated quasistatic strain rate. The actual bending stiffness of the bones was determined using four-point bending tests. Comparison of the bending stiffness estimated from the pQCT data and the mechanical bending stiffness revealed excellent correlation (R2=0.96). The bending stiffness from the pQCT data was on average 103% of that obtained from the four-point bending tests. The results indicate that pQCT data can be used to accurately determine the bending stiffness of normal bone. Possible applications include temporal quantification of fracture healing and risk management of osteoporosis or other bone pathologies.     

Increased training loads do not magnify cancellous bone gains with rodent jump resistance exercise

This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cancellous bone of the proximal tibia metaphysis (PTM) and femoral neck (FN). Sprague-Dawley rats (male, 6 mo old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or sedentary cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE during 5 wk of training. PTM cancellous volumetric bone mineral density (vBMD), assessed by in vivo peripheral quantitative computed tomography scans, significantly increased in both exercise groups (+9%; P < 0.001), resulting in part from 130% (HRE; P = 0.003) and 213% (LRE; P < 0.0001) greater bone formation (measured by standard histomorphometry) vs. CC. Additionally, mineralizing surface (%MS/BS) and mineral apposition rate were higher (50-90%) in HRE and LRE animals compared with controls. PTM bone microarchitecture was enhanced with LRE, resulting in greater trabecular thickness (P = 0.03) and bone volume fraction (BV/TV; P = 0.04) vs. CC. Resorption surface was reduced by nearly 50% in both exercise paradigms. Increased PTM bone mass in the LRE group translated into a 161% greater elastic modulus (P = 0.04) vs. CC. LRE and HRE increased FN vBMD (10%; P < 0.0001) and bone mineral content (～ 20%; P < 0.0001) and resulted in significantly greater FN strength vs. CC. For the vast majority of variables, there was no difference in the cancellous bone response between the two exercise groups, although LRE resulted in significantly greater body mass accrual and bone formation response. These results suggest that jumping at minimal resistance provides a similar anabolic stimulus to cancellous bone as jumping at loads exceeding body mass.     

Bone mineral density and microarchitecture in participants of a 105-day experiment in isolated environment

A study on the bone system state in healthy volunteers has been performed before and after 105-day experiment in hermetically isolated environment (the Mars-105 experiment) using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). The values of bone mineral density (BMD), volumetric bone mineral density (VBMD), and bone structural characteristics of distal segments in radius and tibia have been evaluated. No significant DXA changes have been revealed in segments of skeleton critically important in terms of biomechanics. Microarchitectural deterioration (a decrease in the trabecula number and increase in the bone tissue heterogeneity) has been found using the pQCT technique in the radius of the majority of subjects. A VBMD decrease has been revealed for both cortical and trabecular bones in tibia, along with an unexpected trabecular bone improvement in the form of an increase in the trabecula quantity and decrease in bone tissue heterogeneity. Comprehensive studies, including estimation of projective and volumetric bone mineral densities (the bone mineral content) and bone structural characteristics (bone quality) are required to have a clear view on the changes in the bone system under the conditions of a simulation experiment.     

Distal skeletal tibia assessed by HR-pQCT is highly correlated with femoral and lumbar vertebra failure loads

Dual energy X-ray absorptiometry (DXA) is the standard for assessing fragility fracture risk using areal bone mineral density (aBMD), but only explains 60–70% of the variation in bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides 3D-measures of bone microarchitecture and volumetric bone mineral density (vBMD), but only at the wrist and ankle. Finite element (FE) models can estimate bone strength with 86–95% precision. The purpose of this study is to determine how well vBMD and FE bone strength at the wrist and ankle relate to fracture strength at the hip and spine, and to compare these relationships with DXA measured directly at those axial sites. Cadaveric samples (radius, tibia, femur and L4 vertebra) were compared within the same body. The radius and tibia specimens were assessed using HR-pQCT to determine vBMD and FE failure load. aBMD from DXA was measured at the femur and L4 vertebra. The femur and L4 vertebra specimens were biomechanically tested to determine failure load. aBMD measures of the axial skeletal sites strongly correlated with the biomechanical strength for the L4 vertebra (r = 0.77) and proximal femur (r = 0.89). The radius correlated significantly with biomechanical strength of the L4 vertebra for vBMD (r = 0.85) and FE-derived strength (r = 0.72), but not with femur strength. vBMD at the tibia correlated significantly with femoral biomechanical strength (r = 0.74) and FE-estimated strength (r = 0.83), and vertebral biomechanical strength for vBMD (r = 0.97) and FE-estimated strength (r = 0.91). The higher correlations at the tibia compared to radius are likely due to the tibia’s weight-bearing function.     

A nonlinear finite element model validation study based on a novel experimental technique for inducing anterior wedge-shape fractures in human vertebral bodies in vitro

Vertebral compression fracture is a common medical problem in osteoporotic individuals. The quantitative computed tomography (QCT)-based finite element (FE) method may be used to predict vertebral strength in vivo, but needs to be validated with experimental tests. The aim of this study was to validate a nonlinear anatomy specific QCT-based FE model by using a novel testing setup. Thirty-seven human thoracolumbar vertebral bone slices were prepared by removing cortical endplates and posterior elements. The slices were scanned with QCT and the volumetric bone mineral density (vBMD) was computed with the standard clinical approach. A novel experimental setup was designed to induce a realistic failure in the vertebral slices in vitro. Rotation of the loading plate was allowed by means of a ball joint. To minimize device compliance, the specimen deformation was measured directly on the loading plate with three sensors. A nonlinear FE model was generated from the calibrated QCT images and computed vertebral stiffness and strength were compared to those measured during the experiments. In agreement with clinical observations, most of the vertebrae underwent an anterior wedge-shape fracture. As expected, the FE method predicted both stiffness and strength better than vBMD (R² improved from 0.27 to 0.49 and from 0.34 to 0.79, respectively). Despite the lack of fitting parameters, the linear regression of the FE prediction for strength was close to the 1:1 relation (slope and intercept close to one (0.86 kN) and to zero (0.72 kN), respectively). In conclusion, a nonlinear FE model was successfully validated through a novel experimental technique for generating wedge-shape fractures in human thoracolumbar vertebrae.     

Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density,fractures, and syndesmophytes

Introduction

Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density.

Methods

High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls.

Results

The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (r_S = 0.762; P < 0.001), and tibia (r_S = 0.712; P < 0.001).When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016).mSASSS correlated negatively with trabecular vBMD in lumbar spine (r_S = -0.620; P < 0.001), radius (r_S = -0.400; p = 0.001) and tibia (r_S = -0.475; p < 0.001) and also with trabecular thickness in radius (r_S = -0.528; P < 0.001) and tibia (r_S = -0.488; P < 0.001).Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (r_S = 0.636; P < 0.001).

Conclusions

Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS.     

Subject-specific mechanical properties of vertebral cancellous bone assessed using a low-dose X-ray device

ObjectivesAccording to the inter-individual variability of bone mechanical properties, subject-specific evaluation of the cancellous bone Young's modulus is needed to build finite-element models predicting vertebral strength with accuracy. Relationships based on the density assessed by quantitative computed tomography were proposed. However, quantitative computed tomography is not always suited for the analysis of the whole spine for patients’ follow-up because of the high radiation dose. Hence, this study aims at evaluating the mechanical properties of the vertebral cancellous bone using a low-dose X-ray device.Material and methodsNineteen vertebrae were considered. Biplanar radiographs were made using the low-dose EOS^® system with a dual-energy modality to evaluate antero-posterior and lateral areal bone mineral densities. A cylindrical sample was extracted from each vertebral body and tested until failure to assess the Young's modulus and the ultimate stress of the vertebral cancellous bone.Results and discussionMechanical properties were significantly related to the EOS^® areal densities. On one hand, the relationships remained less predictive than those based on quantitative computed tomography, but on the other hand, they better predict mechanical properties than previous studies using dual X-ray absorptiometry (clinical gold standard system for density assessment).ConclusionThe study shows the feasibility to predict the Young's modulus of the vertebral cancellous bone from the whole vertebral areal bone mineral density (BMD). It gives promising prospects to build finite-element models, including both subject-specific geometry and subject-specific mechanical properties by using a low-dose X-ray device for regions where high radiation doses would limit tomography assessment possibilities.     

Advanced imaging of the macrostructure and microstructure of bone

Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The considerable potential biological differences between the peripheral appendicular skeleton and the central axial skeleton have to be addressed further. Finally, the relative merits of these sophisticated imaging techniques have to be weighed with respect to their applications as diagnostic procedures requiring high accuracy or reliability on one hand and their monitoring applications requiring high precision or reproducibility on the other.     

Variations in morphological and biomechanical indices at the distal radius in subjects with identical BMD

Determination of osteoporotic status is based primarily on areal bone mineral density (aBMD) obtained through dual X-ray absorptiometry (DXA). However, many fractures occur in patients with T-scores above the WHO threshold of osteoporosis, in part because DXA measures are insensitive to biomechanically important alterations in bone quality. The goal of this study was to determine--within groups of subjects with identical radius aBMD values--the extant variation in densitometric, geometric, microstructural, and biomechanical parameters. High resolution peripheral quantitative computed tomography (HR-pQCT) and DXA radius data from males and females spanning large ranges in age, osteoporotic status, and anthropometrics were compiled. 262 distal radius datasets were processed for this study. HR-pQCT scans were analyzed according to the manufacturer's standard clinical protocol to quantify densitometric, geometric, and microstructural indices. Micro-finite element analysis was performed to calculate biomechanical indices. Factor of risk of wrist fracture was calculated. Simulated aBMD calculated from HR-pQCT data was used to group scans for evaluation of variation in quantified indices. Indices reflecting the greatest variation within aBMD level were BMD in the central portion of the trabecular compartment (max CV 142), trabecular heterogeneity (max CV 90), and intra-cortical porosity (max CV 151). Of the biomechanical indices, cortical load fraction had the greatest variation (max CV 38). Substantial variations in indices reflecting density, structure, and biomechanical competence exist among subjects with identical aBMD levels. Overlap of these indices among osteoporotic status groups reflects the reported incidence of osteoporotic fracture in subjects classified as osteopenic or normal.     

pQCT provides better prediction of canine femur breaking load than does DXA

Our study was designed to examine the validity of dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) measurements as predictors of whole bone breaking strength in beagle femora. DXA was used to determine the bone mineral content, bone area, and 'areal' bone mineral density. PQCT was used to determine the cross-sectional moments of inertia, volumetric densities of the bone, and to calculate bone strength indices based on bone geometry and density. A three-point bending mechanical test was used to determine maximal load. Three variables from the pQCT data set explained 88% of the variance in maximal load, with the volumetric bone mineral density explaining 32% of the variance. The addition of the volumetric cortical density increased the adjusted r(2) to 0.601 (p=0.001) and the addition of an index created by multiplying volumetric cortical bone density by the maximum cross-sectional moment of inertia made further significant (p<0.001) improvements to an adjusted r(2) of 0.877. In comparison, when only the DXA variables were considered in a multiple regression model, areal bone mineral density was the only variable entered and explained only 51% (p<0.001) of the variance in maximal load. These results suggest that pQCT can better predict maximal load in whole beagle femora since pQCT provides information on the bone's architecture in addition to its volumetric density.     

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats.

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.     

Mechanical assessment of effects of grape seed proanthocyanidins extract on tibial bone diaphysis in rats

We studied the effects of grape seed proanthocyanidins extract (GSPE) given as a ratio of 3 mg in 100 g in a standard diet, on the tibial bone diaphysis in low-calcium fed rats. Measurements of bone density, mineral content, geometry, and bone strength using peripheral quantitative computed tomography (pQCT). Further, the whole tibia bones were tested for mechanical resistance using a material-testing machine, and mineral elements were also determined. Forty male Wistar rats, 5 weeks old, were divided into control (Co), low-calcium diet (LC), low-calcium diet . standard diet (LCS), and low-calcium diet . standard diet with supplementary GSPE (LCSG) groups. We found no significant differences in body weight among the 4 groups, whereas all of the bone parameters in LC were significantly lower than those in Co (p<0.01, except in periosteal perimeter (Peri) p<0.05). The cortical bone mineral content (CtBMC), cortical bone density (CtvBMD) and Peri in LCSG were significantly higher than those in LCS (p<0.01; p<0.01; p<0.05, respectively). All bone parameters in LCSG were significantly higher than those in LC (p<0.01, except in Peri, and stress strain index to reference axis x (xSSI) p<0.05)). In addition, Ca, P, and Zn contents in LCSG were significantly higher than those in LCS (p<0.01; p<0.01; p<0.05, respectively). Our results suggest that GSPE included in a diet mixture with calcium has a beneficial effect on bone formation and bone strength for the treatment of bone debility caused by a low level of calcium.