Trabecular Bone Stiffness Research Articles

Characterization of Microarchitectures, Stiffness and Strength of Human Trabecular Bone Using Micro-Computed Tomography (Micro-CT) Scans

The present work presents evaluation and experimental verification of the use of X-ray computed tomographic microscopy (micro-CT) for accurate characterization of geometry, microarchitecture, and stiffness properties of bones. These properties are crucial for designing and building optimized implants for joint and dental reconstruction applications. High-resolution micro-CT scans would provide more detailed and accurate information about the microarchitecture and density distribution across patient bones. Nevertheless, micro-CT applications on live patients require invasive procedures involving small bone biopsy specimens. Alternatively, micro-CT could be used on samples collected from selected cadavers of different age, gender, and race groups to establish a database that could be used for providing useful microarchitecture information. The micro-CT scans of investigated bone samples reveal that the trabecular bone is anisotropic and heterogeneous. The results also showed considerable degree of parametric variability and uncertainty on microarchitecture and stiffness properties of patient’s trabecular bone.

Quantitative increase in T regulatory cells enhances bone remodeling in osteogenesis imperfecta

SummaryOsteogenesis imperfecta (OI) is characterized by repeated bone fractures. Recent studies have shown that T lymphocytes and regulatory T cells (Tregs) regulate the functions of osteoclasts and osteoblasts, thus playing a role in bone turnover. We demonstrate an activated effector phenotype and higher secretion of pro-inflammatory cytokines, IFN-γ, and TNF-α in OI peripheral T cells as compared with wild-type (WT). Suppressive Tregs (spleen and thymus) were qualitatively similar, whereas there was a quantitative decrease in OI versus WT. Restoring Treg numbers by systemic transplantation in OI mice resulted in reduced T cell activation and effector cytokine secretion that correlated with significant improvements in tibial trabecular and cortical bone parameters and stiffness of femur, along with increased osteoblast mineralization and decreased osteoclast numbers. Therefore, Tregs can dampen the pro-inflammatory environment and enhance bone remodeling in OI mice. Thus, this study will be helpful in developing future autologous immunotherapy-based treatment modalities for OI.

The effect of Staphylococcus aureus exposure on white-tailed deer trabecular bone stiffness and yield

With a growing number of osteomyelitis diagnoses, many of which are linked to Staphylococcus aureus (S. aureus), it is imperative to understand the pathology of S. aureus in relation to bone to provide better diagnostics and patient care. While the cellular mechanisms of S. aureus and osteomyelitis have been studied, little information exists on the biomechanical effects of such infections. The aim of this study was to determine the effect of S. aureus exposure on the stiffness and yield of trabecular bone tissue. S. aureus-ATCC-12600, a confirmed biofilm producer, along with one hundred and three trabecular cubes (5 × 5 × 5 mm) from the proximal tibiae of Odocoileus virginianus (white-tailed deer) were used in this experiment. Bone cubes were disinfected and then swabbed to confirm no residual living microbes or endospore contamination before inoculation with S. aureus (test group) or sterile nutrient broth (control group) for 72 h. All cubes were then tested in compression until yield using an Instron 5942 Single-Column machine. Structural stiffness (N/mm) and yield (MPa) were calculated and compared between the two groups. Our results revealed that acute exposure to S. aureus, within the context of our deer tibia model, does not significantly decrease trabecular bone stiffness or yield. The results of this study may be of value clinically when assessing fracture risks for osteomyelitis or other patients whose cultures test positive for S. aureus.

Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss

Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p < 0.05). Treatment with unformulated or SEDDS-formulated annatto tocotrienol improved cortical bone thickness, preserved bone calcium content, increased bone biomechanical strength and increased antioxidant enzyme activities compared with the ovariectomized group (p < 0.05). Only SEDDS-formulated annatto tocotrienol improved trabecular microstructure, bone stiffness and lowered malondialdehyde level (p < 0.05 vs the ovariectomized group). The improvement caused by annatto tocotrienol was comparable to raloxifene. In conclusion, SEDDS improves the bioavailability and skeletal therapeutic effects of annatto tocotrienol in a rat model of postmenopausal bone loss. This formulation should be tested in a human clinical trial to validate its efficacy.

Evaluation of La(XT), a novel lanthanide compound, in an OVX rat model of osteoporosis

PurposeThe purpose of this study was to evaluate the efficacy and toxicity of a novel lanthanum compound, La(XT), in an ovariectomized (OVX) rat model of osteoporosis. MethodsTwenty-four ovariectomized female Sprague Dawley rats were divided into 3 groups receiving a research diet with/without treatment compounds (alendronate: 3 mg/kg; La(XT) 100 mg/kg) for three months. At the time of sacrifice, the kidney, liver, brain, lung and spleen were collected for histological examination. The trabecular bone structure of the tibiae was evaluated using micro-CT and a three-point metaphyseal mechanical test was used to evaluate bone failure load and stiffness. ResultsNo significant differences were noted in plasma levels of calcium, phosphorus, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) between the La(XT) treatment compared to the non-treated OVX group. Alendronate-treated animals (positive control) showed higher BV/TV, Tb.N and lower Tb.Th and Tb.Sp when compared to the non-treated OVX group. Mechanical analysis indicated that stiffness was higher in the alendronate (32.88%, p = 0.04) when compared to the non-treated OVX group. Failure load did not differ among the groups. ConclusionsNo kidney or liver toxicities of La(XT) treatments were found during the three-month study. The absence of liver and kidney toxicity with drug treatment for 3 months, as well as the increased trabecular bone stiffness are encouraging for the pursuit of further studies with La(XT) for a longer duration of time.

Idealized conductance: A new method to evaluate stiffness of trabecular bone.

Stiffness is an important parameter to evaluate the condition of trabecular bone in biomechanical and clinical research. Microstructural parameters are commonly used to evaluate stiffness, but the accuracy needs to be improved. In this study, the electrical conductance of trabecular bone was calculated based on an idealized condition: trabeculae were electrically conductive and isotropy, other constituents in the trabecular bone were not considered in the simulation. The idealized conductance was calculated to evaluate the stiffness of trabecular bone, and the accuracy was compared with microstructural parameters. Twenty-one cubic trabecular cubes (5 × 5 × 5 mm3 ) from three femoral heads were investigated. Microstructural parameters were measured through Micro-CT scanning. Nominal elastic modulus (E) and idealized conductance (G) of trabecular cubes were measured through micro-finite element analysis. Bone volume fraction (BV/TV) is the major microstructural parameter that determine the stiffness of trabecular bone. The correlation coefficient between BV/TV and E along three directions were 0.815 (X-axis), 0.729 (Y-axis) and 0.914 (Z-axis). The correlation between G and E were stronger (X-axis: r = 0.986, Y-axis: r = 0.986, Z-axis: r = 0.991). A regression model combining different microstructural parameters was built to evaluate stiffness, but the correlation between them were not significantly improved (X-axis: r = 0.831, Y-axis: r = 0.807, Z-axis: r = 0.905). Compared with microstructural parameters, idealized conductance was a better parameter to evaluate stiffness of trabecular bone.

Trabecular microstructure is influenced by race and sex in Black and White young adults.

Lower fracture rates in Black men and women compared to their White counterparts may be explained by favorable bone microstructure in Black individuals. Individual trabecular segmentation (ITS) analysis, which characterizes the alignment and plate- and rod-like nature of trabecular bone using high-resolution peripheral quantitative computed tomography (HR-pQCT), may provide insight into trabecular differences by race/ethnic origin. We determined differences in trabecular bone microarchitecture, connectivity, and alignment according to race/ethnic origin and sex in young adults. We analyzed HR-pQCT scans of 184 adult (24.2 ± 3.4years) women (n = 51 Black, n = 50 White) and men (n = 34 Black, n = 49 White). We used ANCOVA to compare bone outcomes, and adjusted for age, height, and weight. Overall, the effect of race on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race. After adjusting for covariates, Black participants and men of both races had greater trabecular plate volume fraction, plate thickness, plate number density, plate surface area, and greater axial alignment of trabeculae, leading to higher trabecular bone stiffness compared to White participants and women, respectively (p < 0.05 for all). These findings demonstrate that more favorable bone microarchitecture in Black individuals compared to White individuals and in men compared to women is not unique to the cortical bone compartment. Enhanced plate-like morphology and greater trabecular axial alignment, established in young adulthood, may contribute to the improved bone strength and lower fracture risk in Black versus White individuals and in men compared to women.

Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P < 0.05) and the distal femur (-55%, P < 0.05) compared with euthyroid controls. Scl-Ab and ZOL treatment of hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P < 0.05) and was increased fourfold by Sci-Ab (P < 0.001) and threefold by ZOL treatment (P < 0.01). Bone strength based on ultimate load, which was 10% lower in hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P < 0.001). Increased proportion of low mineralized bone seen in hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms.

Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis.

Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2-values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research.

Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures

Postmenopausal women with vertebral fractures have abnormal bone microarchitecture at the distal radius and tibia by HR-pQCT, independent of areal BMD. However, whether trabecular plate and rod microarchitecture is altered in women with vertebral fractures is unknown. This study aims to characterize the abnormalities of trabecular plate and rod microarchitecture, cortex, and bone stiffness in postmenopausal women with vertebral fractures. HR-pQCT images of distal radius and tibia were acquired from 45 women with vertebral fractures and 45 control subjects without fractures. Trabecular and cortical compartments were separated by an automatic segmentation algorithm and subjected to individual trabecula segmentation (ITS) analysis for measuring trabecular plate and rod morphology and cortical bone evaluation for measuring cortical thickness and porosity, respectively. Whole bone and trabecular bone stiffness were estimated by finite element analysis. Fracture and control subjects did not differ according to age, race, body mass index, osteoporosis risk factors, or medication use. Women with vertebral fractures had thinner cortices, and larger trabecular area compared to the control group. By ITS analysis, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity at both the radius and the tibia. Fewer trabecular rods were observed at the radius. Whole bone stiffness and trabecular bone stiffness were 18% and 22% lower in women with vertebral fractures at the radius, and 19% and 16% lower at the tibia, compared with controls. The estimated failure load of the radius and tibia were also reduced in the fracture subjects by 13% and 14%, respectively. In summary, postmenopausal women with vertebral fractures had both trabecular and cortical microstructural deterioration at the peripheral skeleton, with a preferential loss of trabecular plates and cortical thinning. These microstructural deficits translated into lower whole bone and trabecular bone stiffness at the radius and tibia. Our results suggest that abnormalities in trabecular plate and rod microstructure may be important mechanisms of vertebral fracture in postmenopausal women.

Prediction of apparent trabecular bone stiffness through fourth-order fabric tensors

The apparent stiffness tensor is an important mechanical parameter for characterizing trabecular bone. Previous studies have modeled this parameter as a function of mechanical properties of the tissue, bone density, and a second-order fabric tensor, which encodes both anisotropy and orientation of trabecular bone. Although these models yield strong correlations between observed and predicted stiffness tensors, there is still space for reducing accuracy errors. In this paper, we propose a model that uses fourth-order instead of second-order fabric tensors. First, the totally symmetric part of the stiffness tensor is assumed proportional to the fourth-order fabric tensor in the logarithmic scale. Second, the asymmetric part of the stiffness tensor is derived from relationships among components of the harmonic tensor decomposition of the stiffness tensor. The mean intercept length (MIL), generalized MIL (GMIL), and fourth-order global structure tensor were computed from images acquired through microcomputed tomography of 264 specimens of the femur. The predicted tensors were compared to the stiffness tensors computed by using the micro-finite element method ([Formula: see text]FE), which was considered as the gold standard, yielding strong correlations ([Formula: see text] above 0.962). The GMIL tensor yielded the best results among the tested fabric tensors. The Frobenius error, geodesic error, and the error of the norm were reduced by applying the proposed model by 3.75, 0.07, and 3.16%, respectively, compared to the model by Zysset and Curnier (Mech Mater 21(4):243-250, 1995) with the second-order MIL tensor. From the results, fourth-order fabric tensors are a good alternative to the more expensive [Formula: see text]FE stiffness predictions.

Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness – A Case Study on Osteoporosis Rat Bone

Micro-computed tomography (Micro-CT) images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone microarchitectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA) can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of Micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived grayscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two- and three-dimensional bone microarchitecture from sham and ovariectomized (OVX) rats (n = 10/group). A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA, because Micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three-dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation, and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading.

Effect of intraspecimen spatial variation in tissue mineral density on the apparent stiffness of trabecular bone.

This study investigated the effects of intraspecimen variations in tissue mineral density(TMD) on the apparent-level stiffness of human trabecular bone. High-resolution finite element (FE) models were created for each of 12 human trabecular bone specimens,using both microcomputed tomography (lCT) and “gold-standard” synchrotron radiation lCT (SRlCT) data. Our results confirm that incorporating TMD spatial variation reduces the calculated apparent stiffness compared to homogeneous TMD models. This effect exists for both lCT- and SRlCT-based FE models, but is exaggerated in lCT based models. This study provides a direct comparison of lCT to SRlCT data and is thereby able to conclude that the influence of including TMD heterogeneity is overestimated in lCT-based models.

Bone Volume Fraction and Fabric Anisotropy Are Better Determinants of Trabecular Bone Stiffness Than Other Morphological Variables

As our population ages, more individuals suffer from osteoporosis. This disease leads to impaired trabecular architecture and increased fracture risk. It is essential to understand how morphological and mechanical properties of the cancellous bone are related. Morphology-elasticity relationships based on bone volume fraction (BV/TV) and fabric anisotropy explain up to 98% of the variation in elastic properties. Yet, other morphological variables such as individual trabeculae segmentation (ITS) and trabecular bone score (TBS) could improve the stiffness predictions. A total of 743 micro-computed tomography (μCT) reconstructions of cubic trabecular bone samples extracted from femur, radius, vertebrae, and iliac crest were analyzed. Their morphology was assessed via 25 variables and their stiffness tensor (CFE) was computed from six independent load cases using micro finite element (μFE) analyses. Variance inflation factors were calculated to evaluate collinearity between morphological variables and decide upon their inclusion in morphology-elasticity relationships. The statistically admissible morphological variables were included in a multiple linear regression model of the dependent variable CFE. The contribution of each independent variable was evaluated (ANOVA). Our results show that BV/TV is the best determinant of CFE(r(2) adj = 0.889), especially in combination with fabric anisotropy (r(2) adj = 0.968). Including the other independent predictors hardly affected the amount of variance explained by the model (r(2) adj = 0.975). Across all anatomical sites, BV/TV explained 87% of the variance of the bone elastic properties. Fabric anisotropy further described 10% of the bone stiffness, but the improvement in variance explanation by adding other independent factors was marginal (<1%). These findings confirm that BV/TV and fabric anisotropy are the best determinants of trabecular bone stiffness and show, against common belief, that other morphological variables do not bring any further contribution. These overall conclusions remain to be confirmed for specific bone diseases and postelastic properties.

Enhanced individual trabecular repair and its mechanical implications in parathyroid hormone and alendronate treated rat tibial bone.

Combined parathyroid hormone (PTH) and bisphosphonate (alendronate-ALN) therapy has recently been shown to increase bone volume fraction and plate-like trabecular structure beyond either monotherapy. To identify the mechanism through which plate-like structure was enhanced, we used in vivo microcomputed tomography (μCT) of the proximal tibia metaphysis and individual trabecular dynamics (ITD) analysis to quantify connectivity repair (incidences of rod connection and plate perforation filling) and deterioration (incidences of rod disconnection and plate perforation). Three-month-old female, intact rats were scanned before and after a 12 day treatment period of vehicle (Veh, n = 5), ALN (n = 6), PTH (n = 6), and combined (PTH+ALN, n = 6) therapy. Additionally, we used computational simulation and finite element (FE) analysis to delineate the contributions of connectivity repair or trabecular thickening to trabecular bone stiffness. Our results showed that the combined therapy group had greater connectivity repair (5.8 ± 0.5% connected rods and 2.0 ± 0.3% filled plates) beyond that of the Veh group, resulting in the greatest net gain in connectivity. For all treatment groups, increases in bone volume due to thickening (5-31%) were far greater than those due to connectivity repair (2-3%). Newly formed bone contributing only to trabecular thickening caused a 10%, 41%, and 69% increase in stiffness in the ALN, PTH, and PTH+ALN groups, respectively. Moreover, newly formed bone that led to connectivity repair resulted in an additional improvement in stiffness, with the highest in PTH+ALN (by an additional 12%), which was significantly greater than either PTH (5.6%) or ALN (4.5%). An efficiency ratio was calculated as the mean percent increase in stiffness divided by mean percent increase in BV for either thickening or connectivity repair in each treatment. For all treatments, the efficiency ratio of connectivity repair (ALN: 2.9; PTH: 3.4; PTH+ALN: 4.4) was higher than that due to thickening (ALN: 2.0; PTH: 1.7; PTH+ALN: 2.2), suggesting connectivity repair required less new bone formation to induce larger gains in stiffness. We conclude that through rod connection and plate perforation filling PTH+ALN combination therapy improved bone stiffness in a more efficient and effective manner than either monotherapy.

Local treatment of osteoporosis with alendronate-loaded calcium phosphate cement

Background A new treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures. We term this strategy as the “local treatment of osteoporosis”. The study was performed to investigate the effect of alendronate-loaded calcium phosphate cement (CPC) as a novel drug delivery system for local treatment of osteoorosis. Methods An in vitro study was performed using CPC fabricated with different concentrations of alendronate (ALE, 0, 2, 5, 10 weight percent (wt%)). The microstructure, setting time, infrared spectrum, biomechanics, drug release, and biocompatibility of the composite were measured in order to detect changes when mixing CPC with ALE. An in vivo study was also performed using 30 Sprague-Dawley rats randomly divided into six groups: normal, Sham (ovariectomized (OVX) + Sham), CPC with 2% ALE, 5%ALE, and 10% ALE groups. At 4 months after the implantation of the composite, animals were sacrificed and the caudal vertebrae (levels 4–7) were harvested for micro-CT examination and biomechanical testing. Results The setting time and strength of CPC was significantly faster and greater than the other groups. The ALE release was sustained over 21 days, and the composite showed good biocompatibility. In micro-CT analysis, compared with the Sham group, there was a significant increase with regard to volumetric bone mineral density (BMD) and trabecular number (Tb.N) in the treated groups (P &lt;0.05). Trabecular spacing (Tb.Sp) showed a significant increase in the Sham group compared to other groups (P &lt;0.01). However, trabecular thickness (Tb.Th) showed no significant difference among the groups. In biomechanical testing, the maximum compression strength and stiffness of trabecular bone in the Sham group were lower than those in the experimental groups. Conclusions The ALE-loaded CPC displayed satisfactory properties in vitro, which can reverse the OVX rat vertebral trabecular bone microarchitecture and biomechanical properties in vivo.

Effect of a combination GOS/FOS® prebiotic mixture and interaction with calcium intake on mineral absorption and bone parameters in growing rats.

Increasing calcium intake is the most effective strategy for avoiding Ca deficit. However, if intake remains inadequate, improving Ca absorption becomes an important tool to optimize Ca homeostasis and bone health. The effect of a mixture of GOS/FOS(®) 9:1 added to a normal- or low-Ca diets on Ca absorption and bone mineralization, density and structure was investigated, in a model of growing rats. Several colonic parameters to help support the findings were also evaluated. Weanling Wistar rats received one of the four experimental AIN-93G diets: C5: 0.5% Ca; C3: 0.3% Ca; P5: 0.5% Ca + 5.3% GOS/FOS(®); P3: 0.3% Ca + 5.3% GOS/FOS(®) until 50 days (T = 50). At T = 50, lactobacillus and cecum weights were higher, whereas cecum pH was lower in P5 and P3 versus C5 and C3 (p < 0.001). At T = 50, fecal Ca, Mg and P were lower and their absorptions (mg/dL) were higher in P5 and P3 versus C5 and C3, respectively (p < 0.05). Ca, Mg and P absorption % was higher in P5 and P3 versus C5 and C3 (p < 0.001). Femur Ca and P content, bone mineral content, trabecular bone mineral density, tibia length, bone volume, osteoblast surface, stiffness and elastic modulus were higher in P5 and P3 versus C5 and C3 (p < 0.05). Despite the lower Ca content, P3 group reached similar values than C5 in all these latter parameters. Supplementing diets with the GOS/FOS(®) mixture increased bone mineralization, density and structure due to an increase in Ca, P and Mg absorptions. Thus, this prebiotic mixture may help to improve bone development in a period of high calcium requirements.

Bone density, microarchitecture and stiffness in Caucasian and Caribbean Hispanic postmenopausal American women.

Hispanic Americans of Caribbean origin are a fast-growing subset of the US population, but there are no studies on bone density, microstructure and biomechanical integrity in this minority group. In this study, we aimed to compare Caucasian and Caribbean Hispanic postmenopausal American women with respect to these characteristics. Thirty-three Caribbean Hispanics were age-matched to thirty-three Caucasian postmenopausal women. At the lumbar spine, the Hispanic women had significantly lower areal bone mineral density (aBMD). At the radius by high-resolution peripheral quantitative computed tomography (HR-pQCT), there were minimal differences between Hispanic and Caucasian women. At the tibia, Hispanic women had lower trabecular volumetric bone density and trabecular number, and higher trabecular separation. Individual trabecula segmentation (ITS) analyses indicated that at the tibia, Hispanic women not only had significantly lower bone volume fraction, but also had significantly lower rod bone volume fraction, plate trabecular number, rod trabecular number and lower plate–plate, plate–rod and rod–rod junction densities compared to Caucasian women. The differences in bone quantity and quality contributed to lower whole bone stiffness at the radius, and both whole bone and trabecular bone stiffness at the tibia in Hispanic women. In conclusion, Hispanic women had poorer bone mechanical and microarchitectural properties than Caucasian women, especially at the load-bearing distal tibia.

3D image registration is critical to ensure accurate detection of longitudinal changes in trabecular bone density, microstructure, and stiffness measurements in rat tibiae by in vivo microcomputed tomography (μCT)

In the recent decade, in vivo μCT scanners have become available to monitor temporal changes in rodent bone in response to diseases and treatments. We investigated short-term and long-term precision of in vivo μCT measurements of trabecular bone density, microstructure and stiffness of rat tibiae and tested whether they can be improved by 3D image registration. Rats in the short-term precision group underwent baseline and follow-up scans within the same day (n=15) and those in the long-term precision group were scanned at day 0 and day 14 (n=16) at 10.5μm voxel size. A 3D image-registration scheme was applied to register the trabecular bone compartments of baseline and follow-up scans. Prior to image registration, short-term precision ranged between 0.85% and 2.65% in bone volume fraction (BV/TV), trabecular number, thickness, and spacing (Tb.N*, Tb.Th*, Tb.Sp*), trabecular bone mineral density and tissue mineral density (Tb.BMD, and Tb.TMD), and was particularly high in structure model index (SMI), connectivity density (Conn.D), and stiffness (4.29%–8.83%). Image registration tended to improve the short-term precision, but the only statistically significant improvement was in Tb.N*, Tb.TMD, and stiffness. On the other hand, unregistered comparisons between day-0 and day-14 scans suggested significant increases in BV/TV, Tb.N*, Tb.Th*, Conn.D, and Tb.BMD and decrease in Tb.Sp* and SMI. However, the percent change in each parameter from registered comparisons was significantly different from unregistered comparisons. Registered results suggested a significant increase in BV/TV, Tb.BMD, and stiffness over 14days, primarily caused by increased Tb.Th* and Tb.TMD. Due to the continuous growth of rodents, the direct comparisons between the unregistered baseline and follow-up scans were driven by changes due to global bone modeling instead of local remodeling. Our results suggested that 3D image registration is critical for detecting changes due to bone remodeling activities in rodent trabecular bone by in vivo μCT imaging.

Teriparatide for Idiopathic Osteoporosis in Premenopausal Women: A Pilot Study

Premenopausal women with idiopathic osteoporosis (IOP) have abnormal cortical and trabecular bone microarchitecture. The purpose of this study was to test the hypotheses that teriparatide increases bone mineral density (BMD) and bone formation and improves trabecular microarchitecture and stiffness in women with IOP. This was an open-label pilot study. The setting was a tertiary care referral center. Participants were 21 premenopausal women with unexplained fragility fractures or low BMD. Teriparatide was administered at 20 μg daily for 18 to 24 months. The primary endpoint was within-subject percent change in lumbar spine BMD. Secondary endpoints included percent change in hip and forearm BMD, transiliac biopsy parameters (trabecular bone volume, microarchitecture, stiffness, and adipocytes), serum N-terminal propeptide of procollagen type 1 (P1NP), and C-telopeptide. BMD increased at the spine (10.8 ± 8.3% [SD]), total hip (6.2 ± 5.6%), and femoral neck (7.6 ± 3.4%) (all P < .001). Serum P1NP doubled by 1 month, peaked at 6 months, and returned to baseline by 18 to 24 months. Transiliac biopsies demonstrated significant increases in cortical width and porosity and trabecular bone volume and number increased, mirrored by a 71% increase in trabecular bone stiffness (P < .02-.001). Adipocyte area, perimeter, and volume/marrow volume decreased, with no change in adipocyte number. Four women had no increase in BMD and a blunted, delayed increase in serum P1NP. Nonresponders had markedly lower baseline bone formation rate (0.002 ± 0.001 vs 0.011 ± 0.006 mm²/mm/y; P < .001) and higher serum IGF-1 (208 ± 54 vs 157± 44 ng/mL; P = .03). Teriparatide was associated with increased spine and hip BMD and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.