Bone Microstructural Properties Research Articles

The Potential Therapeutic Effects of Platelet-Derived Biomaterials on Osteoporosis: A Comprehensive Review of Current Evidence

Osteoporosis is a chronic multifactorial condition that affects the skeletal system, leading to the deterioration of bone microstructure and an increased risk of bone fracture. Platelet-derived biomaterials (PDBs), so-called platelet concentrates, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), have shown potential for improving bone healing by addressing microstructural impairment. While the administration of platelet concentrates has yielded positive results in bone regeneration, the optimal method for its administration in the clinical setting is still debatable. This comprehensive review aims to explore the systemic and local use of PRP/PRF for treating various bone defects and acute fractures in patients with osteoporosis. Furthermore, combining PRP/PRF with stem cells or osteoinductive and osteoconductive biomaterials has shown promise in restoring bone microstructural properties, treating bony defects, and improving implant osseointegration in osteoporotic animal models. Here, reviewing the results of in vitro and in vivo studies, this comprehensive evaluation provides a detailed mechanism for how platelet concentrates may support the healing process of osteoporotic bone fractures.

The influence of body size and phylogeny on trabecular microstructure in the proximal femur and humerus of rodents and primates

Life history theory states that organisms maximize their fitness via energetic trade‐offs between various biological functions. It has been well‐established that life history strategy is related to intraspecific variation in body size and that body size predicts some bone microstructural properties, but the relationship between life history strategy and skeletal variation has not been sufficiently examined across multiple mammalian clades. Generally, small‐bodied mammals have “fast” life histories and faster growth rates than large‐bodied mammals, meaning small mammals deposit bone tissue at a faster rate, which may affect skeletal morphology. Therefore, the goal of this study was to conduct a preliminary analysis of trabecular bone structure in the rodent and primate humerus and femur to evaluate the influence of life history traits, particularly body size, on bone properties in a phylogenetically diverse sample. Using a sample of 67 size‐matched adult rodent and primate individuals from 8 extant rodent genera (N=26) and 10 extant primate genera (N=41) ranging in body size from 0.04kg to 70kg, we analyzed trabecular bone structure in the proximal femoral and humeral head. Regression analyses were used to assess associations between trabecular bone properties and body size and one‐way ANOVAs were used to compare bone properties between rodents and primates across three size‐matched classes.Regression results are consistent with previous primate and mammal studies. Bone volume fraction (BV/TV) scales with weak positive allometry in both groups and both elements except for the rodent humerus, which scales isometrically. Degree of anisotropy (DA) varies across all groups and shows no consistent relationship with body size. Trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) increase with body size, while connectivity density (Conn.D) and bone surface density (BS/BV) decrease with body size across both clades and elements. In both groups and both bones, Tb.Th, Tb.Sp, and Conn.D scale with strong negative allometry while BS/BV scales with strong positive allometry. ANOVAs reveal that Tb.Th and Tb.Sp are higher in the primate femur than in the rodent femur for medium and large size classes, while Conn. D is higher in the rodent femur for medium and large size classes. Other bone properties do not show consistent patterns of differences between primates and rodents. Overall, while overlapping confidence intervals for all slopes suggest body size scales similarly with these bone properties across clades, ANOVA results suggest that medium and large bodied rodents have thinner, more numerous trabeculae in the femur compared to similarly‐sized primates. Further investigation is necessary to elucidate the biological significance of this result and the underlying mechanisms driving the observed phenomenon.

Selenium nanoparticles stimulate osteoblast differentiation via BMP-2/MAPKs/β-catenin pathway in diabetic osteoporosis.

Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit the bone loss involved in hyperglycemia-induced osteoporosis. Methods: Rat osteoblastic UMR-106 cells were used for in vitro studies and female Sprague-Dawley rats were used for type 2 diabetes-associated osteoporosis in vivo study. Results:In vitro studies show that SeNPs promote osteoblast differentiation via modulating alkaline phosphatase (ALP) activity, andpromoting calcium nodule formation and collagen content. The authorsalso provide evidence regarding the involvement of the BMP-2/MAPKs/β-catenin pathway in preventing diabetic osteoporosis. Further, in vivo and ex vivo studies suggested that SeNPs can preserve mechanical and microstructural properties of bone. Conclusion: To the best of our knowledge, thisstudy provides the first evidence regarding the therapeutic benefits of SeNPs in preventing diabetes-associated bone fragility.

Sex differences in systemic bone and muscle loss following femur fracture in mice.

Fracture induces systemic bone loss in mice and humans, and a first (index) fracture increases the risk of future fracture at any skeletal site more in men than women. The etiology of this sex difference is unknown, but fracture may induces a greater systemic bone loss response in men. Also sex differences in systemic muscle loss after fracture have not been examined. We investigated sex differences in systemic bone and muscle loss after transverse femur fracture in 3-month-old male and female C57BL/6 J mice. Whole-body and regional bone mineral content and density (BMC and BMD), trabecular and cortical bone microstructure, muscle contractile force, muscle mass, and muscle fiber size were quantified at multiple time points postfracture. Serum concentrations of inflammatory cytokines (IL-1β, IL-6, and TNF-α) were measured 1-day postfracture. One day postfracture, IL-6 and Il-1B were elevated in fracture mice of both sexes, but TNF-α was only elevated in male fracture mice. Fracture reduced BMC, BMD, and trabecular bone microstructural properties in both sexes 2 weeks postfracture, but declines were greater in males. Muscle contractile force, mass, and fiber size decreased primarily in the fractured limb at 2 weeks postfracture and females showed a trend toward greater muscle loss. Bone and muscle properties recovered by 6 weeks postfracture. Overall, postfracture systemic bone loss is greater in men, which may contribute to sex differences in subsequent fracture risk. In both sexes, muscle loss is primarily confined to the injured limb and fracture may induce greater inflammation in males.

Calcium Bioavailability in the Soluble and Insoluble Fibers Extracted from Opuntia ficus indica at Different Maturity Stages in Growing Rats.

Childhood and adolescence are crucial stages of life for bone health. Therefore, an adequate calcium intake and a healthy life style constitute the main strategies to prevent the risk of osteoporosis-related fractures during adulthood. It has been demonstrated that inclusion of indigestible carbohydrates in foods can help improve calcium absorption in growing stages. The objective of this study was to evaluate the effect of supplementation of soluble and insoluble fibers extracted from O. ficus indica cladodes on calcium bioavailability. Male Wistar rats 4-week old were fed diets added with soluble and insoluble fibers extracted from O. ficus indica cladodes at early and late maturity stages, as the only source of calcium. The mineral content, bone mineral density (BMD), physical, microstructural, and biomechanical properties of rat femurs were determined. The bones of rats fed with diets containing a soluble fiber extracted from O. ficus indica at early and late maturity stages exhibited better bone properties (resistance to fracture, microarchitecture, and calcium content) than control rats and rats fed with an insoluble fiber from O. ficus indica cladodes at both maturity stages. As expected, based on these results, the BMD values were higher in adolescent and pubertal rats fed with a diet containing the O. ficus indica soluble fiber. These results demonstrate that the soluble fiber from O. ficus indica cladodes is indeed a valuable source of bioavailable calcium, which contributes to improve physical, densitometric, biomechanical, and microstructural properties of bone in growing rats.

Bifidobacterium pseudocatenulatum CECT 7765 reverses the adverse effects of diet-induced obesity through the gut-bone axis.

Obesity and the associated chronic metabolic diseases (e.g., type-2 diabetes) adversely affect bone metabolism and health. Gut microbiota is considered to be involved in the pathophysiology of obesity and also represents a therapeutic target. This study has investigated the contribution of diet-induced obesity to alterations in bone health and metabolism and whether these could be restored by oral administration of Bifidobacterium pseudocatenulatum CECT 7765. To do so, adult male wild-type C57BL-6 mice were fed either a standard or high-fat diet (HFD), supplemented or not with B. pseudocatenulatum CECT 7765 (109 CFU/day) for 14 weeks. Effects on bone mass density (BMD), bone mineral content, bone remodeling, bone structure and gene expression were assessed. In HFD-fed mice, bone microstructural properties at the distal femur showed deteriorated trabecular architecture in bone volumetric fraction, trabecular number and trabecular pattern factor. Besides, the HFD reduced the volumetric bone mineral density in the trabecular bone, but not in the cortical bone. All these bone microstructural alterations found in obese mice were reversed by B. pseudocatenulatum CECT 7765. Administration of the bacterium increased (p < .05) the Wnt/β-catenin pathway gene expression, which could mediate effects on BMD. Bifidobacterium pseudocatenulatum CECT 7765 supplementation increased (p < .05) serum osteocalcin (OC, bone formation parameter), and decreased serum C-terminal telopeptide (CTX) (p < .01) and parathormone (PTH) (p < .05) (both bone resorption parameters). It also altered the microstructure of the femur. In summary, HFD interfered with the normal bone homeostasis leading to increased bone loss. In obese mice, B. pseudocatenulatum CECT 7765 lowered bone mass loss and enhanced BMD by decreasing bone resorption and increasing bone formation.

CT-Based Characterization of Transverse and Longitudinal Trabeculae and Its Applications.

Osteoporosis is a common age-related disease characterized by reduced bone mineral density (BMD), micro-structural deterioration, and enhanced fracture-risk. Although, BMD is clinically used to define osteoporosis, there are compelling evidences that bone micro-structural properties are strong determinants of bone strength and fracture-risk. Reliable measures of effective trabecular bone (Tb) micro-structural features are of paramount clinical significance. Tb consists of transverse and longitudinal micro-structures, and there is a hypothesis that transverse trabeculae improve bone strength by arresting buckling of longitudinal trabeculae. In this paper, we present an emerging clinical CT-based new method for characterizing transverse and longitudinal trabeculae, validate the method, and examine its application in human studies. Specifically, we examine repeat CT scan reproducibility, and evaluate the relationships of these measures with gender and body size using human CT data from the Iowa Bone Development Study (IBDS) (n = 99; 49 female). Based on a cadaveric ankle study (n = 12), both transverse and longitudinal Tb measures are found reproducible (ICC > 0.94). It was observed in the IBDS human data that males have significantly higher trabecular bone measures than females for both inner (p < 0.05) and outer (p < 0.01) regions of interest (ROIs). For weight, Spearman correlations ranged 0.43-0.48 for inner ROI measures and 0.50-0.52 for outer ROI measures for females versus 0.30-0.34 and 0.23-0.25 for males. Correlation with height was lower (0.36-0.39), but still mostly significant for females. No association of trabecular measures with height was found for males.

Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications

Hereditary hemochromatosis (HHC) is characterized by excessive intestinal iron absorption resulting in a pathological increase of iron levels. Parenchyma damage may be a consequence of iron deposition in affected organs (e.g., liver, pancreas, gonads) as well as bones and joints, leading to osteoporosis with increased fracture risk and arthropathy. Up to date, it is not known whether HHC can also be considered as a risk factor for osteonecrosis. Likewise, the underlying skeletal changes are unknown regarding, e.g., microstructural properties of bone. We aimed to study the spectrum of skeletal complications in HHC and the possible underlying microarchitectural changes. Therefore, we retrospectively analyzed all patients with HHC (n = 10) presenting in our outpatient clinic for bone diseases. In addition to dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) was performed and bone turnover markers, 25-OH-D3, ferritin and transferrin saturation were measured. Cortical volumetric bone mineral density (Ct.BMD) and cortical thickness (Ct.Th) were reduced, whereas trabecular microstructure (Tb.Th) and volumetric bone mineral density (Tb.BMD) were preserved compared to age- and gender-adjusted reference values from the literature. Interestingly, the occurrence of bone complications was age dependent; while younger patients presented with osteonecroses or transient bone marrow edema, patients older than 65 years presented with fractures. Our study provides first insights into altered bone microarchitecture in HHC and sheds new light on the occurrence of osteonecrosis. If available, HR-pQCT is a useful complement to fracture risk assessment and to determine microstructural deterioration and volumetric bone mineralization deficits.

Water proton density in human cortical bone obtained from ultrashort echo time (UTE) MRI predicts bone microstructural properties

PurposeTo investigate the correlations between cortical bone microstructural properties and total water proton density (TWPD) obtained from three-dimensional ultrashort echo time Cones (3D-UTE-Cones) magnetic resonance imaging techniques. Materials and methods135 cortical bone samples were harvested from human tibial and femoral midshafts of 37 donors (61 ± 24 years old). Samples were scanned using 3D-UTE-Cones sequences on a clinical 3T MRI and on a high-resolution micro-computed tomography (μCT) scanner. TWPD was measured using 3D-UTE-Cones MR images. Average bone porosity, pore size, and bone mineral density (BMD) were measured from μCT images at 9 μm voxel size. Pearson's correlation coefficients between TWPD and μCT-based measures were calculated. ResultsTWPD showed significant moderate correlation with both average bone porosity (R = 0.66, p < 0.01) and pore size (R = 0.57, p < 0.01). TWPD also showed significant strong correction with BMD (R = 0.71, p < 0.01). ConclusionsThe presented 3D-UTE-Cones imaging technique allows assessment of TWPD in human cortical bone. This quick UTE-MRI-based technique was capable of predicting bone microstructure differences with significant correlations. Such correlations highlight the potential of UTE-MRI-based measurement of bone water proton density to assess bone microstructure.

Atlases with Arcuate Foramen Present Cortical Bone Thickening That May Contribute to Lower Fracture Risk

To date, no information about the cortical bone microstructural properties in atlas vertebrae with arcuate foramen has been reported. As a result, we aimed to test in an experimental model if there is a cortical bone thickening in an atlas vertebra which has an arcuate foramen that may play a protective role against bone fracture. We analyzed by means of micro-computed tomography the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry atlas vertebrae with arcuate foramen and without arcuate foramen. We also reviewed a case series of 31 posterior atlas arch fractures to correlate the possible presence in the same atlas of both fracture and arcuate foramen. The micro-computed tomography study revealed significant differences in cortical bone thickness (P < 0.001), cortical volume (P < 0.004), and medullary volume (P= 0.013) values between the arcuate foramen vertebrae and the nonarcuate foramen vertebrae. The clinical series found no coexistence in the same vertebra of a posterior atlas arch fractures and the arcuate foramen. An atlas with arcuate foramen presents cortical bone thickening. This advantage in bone microarchitecture seems to contribute to a lower fracture risk compared to subjects without arcuate foramen as no coexistence in the same vertebra of a posterior atlas arch fractures and arcuate foramen was found.

Cortical bone thickening in Type A posterior atlas arch defects: experimental report

Background ContextTo date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. PurposeTo test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Study DesignMicro-computed tomography (CT) study on cadaveric atlas vertebrae. MethodsWe analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. ResultsThe micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. ConclusionsType A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures.

Pull-out strength comparison of a novel expanding fastener against an orthopaedic screw in an ovine vertebral body: an ex-vivo study

The purpose of this study was to mechanically test a novel Unthreaded Expandable Fastener (UEF), manufactured using Selective Laser Melting, which was designed for fixation in the cervical lateral mass. The pull-out strength and stiffness of the prototype UEFs was evaluated in a non-osteoporotic ovine bone model against equivalent screws. The prototype UEF demonstrated a 41% increase in failure force and a 60% reduction in failure force standard deviation compared to the screws. All bone samples were micro CT-scanned and no significant differences in bone microstructural properties was found between the screw and UEF sample sets, indicating that the UEFs may be less sensitive to bone quality variation. This increased performance can potentially translate into improved surgical outcome and reduced surgical risk for lateral mass fixation. With further design optimisation, additional improvement in performance over screws may be possible in future studies.

Three-times-weekly administration of teriparatide improves vertebral and peripheral bone density, microarchitecture, and mechanical properties without accelerating bone resorption in ovariectomized rats.

Daily and weekly administration of teriparatide (PTH1–34) reduces the risk of osteoporotic bone fractures. However, their effects on markers of bone formation and bone resorption differ. These results indicate that the dosing frequency of teriparatide may affect bone metabolism and bone structure, with different effects on bone strength. In the present study, to evaluate the dose-related effects of a low administration frequency of teriparatide on bone status, we investigated the effects of three-times-weekly administration of teriparatide (1.1, 5.6, or 28.2 µg/kg) for 12 months on bone parameters, including bone metabolism markers, bone mineral density (BMD), micro-computed tomography, and bone strength, using 6-month-old ovariectomized (OVX) rats. Three-times-weekly administration of teriparatide dose-dependently increased the BMD of the lumbar vertebra and femur in OVX rats, and increased serum osteocalcin (a marker of bone formation), but not type I collagen C-telopeptide (a marker of bone resorption). The trabecular number and thickness increased in the vertebrae and femur, as in prior reports of daily teriparatide administration in OVX rats. Cortical thickness increased only toward the endocortical side of the femur, unlike with daily administration. Bone strength of the vertebrae and proximal and shaft of the femur was correlated with the changes in BMD and bone structure. These results demonstrate the effects of low frequency, intermittent administration of teriparatide on the biomechanical, and microstructural properties of bone in OVX rats.Electronic supplementary materialThe online version of this article (doi:10.1007/s00223-015-9998-0) contains supplementary material, which is available to authorized users.

Impact of estrogens on atherosclerosis and bone in the apolipoprotein E-deficient mouse model.

The common inflammatory pathophysiology has nourished the hypothesis of a relationship between osteoporosis and cardiovascular disease. Estrogens are key agents in the modulation of both processes. We investigated whether induction of atherosclerosis affects bone and whether estrogens modulate both processes. Female apolipoprotein E-deficient mice (a well-established model of atherogenesis) were ovariectomized or falsely operated and fed either standard diet or high-fat diet (HFD). Six animals were included in each of the four groups. To clarify mechanisms, we treated preosteoblastic MC3T3-E1 cells with mouse serum. Physiological levels of estrogens in falsely operated mice limited atherosclerotic burden in the thoracic aorta, but not in the aortic arch. Bone resorption, as assessed by C-telopeptides, was increased by ovariectomy in animals fed standard diet, but not in animals fed HFD. Bone microstructural properties at the distal femur showed deteriorated trabecular architecture in bone volumetric fraction and trabecular number after ovariectomy, but trabecular pattern factor, trabecular thickness, trabecular spacing, or the structural model index remained unchanged. Changes in cortical parameters were not significant. Volumetric bone mineral density was reduced in trabecular bone, but not in cortical bone, in ovariectomized mice fed standard diet. Preosteoblastic MC3T3-E1 cells exhibited increased cellular proliferation and viability and alkaline phosphatase activity after treatment with sera from animals fed HFD. Endogenous estrogens partially reduce atherogenic burden in female apolipoprotein E-deficient mice. Ovariectomy increases bone resorption, but not under exacerbated proatherogenic conditions induced by HFD. The absence of apolipoprotein E might have an influence on the asymmetric responses of atherogenesis and bone resorption.

Effects of short-term swimming exercise on bone mineral density, geometry, and microstructural properties in sham and ovariectomized rats

Little information exists about the effects of swimming exercise on bone health in ovariectomized animals with estrogen deficiency, which resembles the postmenopausal state and age-related bone loss in humans. This study investigated the effects of swimming exercise on tibia and femur bone mineral density (BMD), geometry, and microstructure in sham and ovariectomized rats. Forty 3-month-old female rats were divided into four groups: sham operated-sedentary control (Sham-control), sham operated with swimming exercise group (Sham-Swim), ovariectomy-sedentary control (OVx-control), and ovariectomy and swimming exercise (OVx-Swim) groups. Swimming sessions were performed by the rats 90 minutes/day for 5 days/week for a total of 8 weeks. At the end of the study, tibial and femoral proximal volumetric total BMD, midshaft cortical volumetric BMD, cross-sectional area, and cross-sectional moment of inertia (MOI), and bone microstructural properties were measured for comparison. Data were analyzed using one-way analysis of variance (ANOVA). The Sham-Swim group exhibited significantly (p < 0.05; one-way ANOVA) greater values in bone geometry parameters, that is, tibial midshaft cortical area and MOI compared to the Sham-control group. However, no significant differences were observed in these parameters between the Ovx-Swim and Ovx-control groups. There were no significant differences in femoral BMD between the Sham-Swim and Sham-control groups. Nevertheless, the Ovx-Swim group elicited significantly (p < 0.05; one-way ANOVA) higher femoral proximal total BMD and improved bone microstructure compared to the Ovx-Sham group. In conclusion, the positive effects of swimming on bone properties in the ovariectomized rats in the present study may suggest that swimming as a non- or low-weight-bearing exercise may be beneficial for enhancing bone health in the postmenopausal population.

Periodontal microstructure change and tooth movement pattern under different force magnitudes in ovariectomized rats: An in-vivo microcomputed tomography study

The purpose of this study was to evaluate the dynamic changes in the periodontal microstructure and the molar displacement pattern during orthodontic tooth movement in ovariectomized rats. Twenty ovariectomized rats received either 100 or 30 g of orthodontic force to induce mesial movement of the maxillary left first molars over 14 days. Ten healthy rats underwent sham operations as controls. Periodontal ligament thickness, alveolar bone microstructural properties, and displacement of the molar were measured with 6 in-vivo microcomputed tomography scans for each sample. The ovariectomized rats that received 100 g of orthodontic force had obvious changes in periodontal ligament thickness at day 1 and poor periodontal ligament thickness recovery from days 5 through 14. The bone volume fraction increased and the trabecular separation decreased significantly in this group at day 3, and obvious bone loss was observed at day 14. Molar linear and angular movements were also higher in this group than in the other 2 groups. Relatively heavier force applications in ovariectomized rats resulted in poor periodontal ligament thickness recovery and local alveolar bone overcompression, and consequently induced undermining resorption and obvious alveolar bone loss; these led to high rates of tooth movement and molar inclination.

The Deleterious Effect of Bariatric Surgery on Cortical and Trabecular Bone Density in the Femurs of Non-obese, Type 2 Diabetic Goto-Kakizaki Rats

The effects of type 2 diabetes on bone mass and microstructure are not clear. The aim of this study was to evaluate bone microstructural properties and volumetric bone mineral density (vBMD) in type 2 diabetic Goto-Kakizaki non-obese rats after gastrojejunal bypass and their relationship with hormonal parameters. We designed an experimental study in Goto-Kakizaki rats with and without gastrojejunal bypass, performing densitometric and microstructural studies of the distal femur using X-ray computed microtomography (micro-CT). Levels of insulin, glucagon, leptin, and glucagon-like peptide-1 (GLP-1) were also determined. We observed reduced cortical (1,488.92 ± 98.2 vs. 1,727.92 ± 133.45 mg/cm(3), p = 0.028) and trabecular (180.8 ± 9 vs. 261.23 ± 45.54 mg/cm(3), p = 0.036) vBMD in operated rats. Bone volume fraction (BV/TV) and trabecular connectivity were reduced in operated rats, while there was a reduction in cortical thickness and an increase in rod-like trabeculae at the expense of plate-like trabeculae. Leptin was reduced (1,042 ± 549 vs. 2,447 ± 1,035 pg/ml, p = 0.05) and GLP-1 increased (1.62 ± 0.32 vs. 0.96 ± 0.1 ng/ml, p = 0.008) but only leptin showed a significant association with vBMD CONCLUSIONS: In type 2 diabetic Goto-Kakizaki rats, gastrojejunal bypass produces a reduction in cortical and trabecular bone mineral density and a deterioration in bone quality that could be explained, in part, by the reduction in leptin levels.

Altered bone fatty acid metabolism in obesity and after diet-induced weight loss

The senescence-accelerated mouse strain P6 (SAMP6) is a model of senile osteoporosis, which possesses many features of senile osteoporosis in humans. So far, little is known about the systemic bone microstructural changes that occur at multiple skeletal sites. In this study, we therefore, investigated site (vertebra, femur and tibia) dependence of bone microstructure and bone mineral density (BMD) in SAMP6 and the normal control mouse (SAMR1) at 5 and 12 months of age using quantitative micro computed tomography (micro-CT) and image analysis software. As compared with SAMR1, the most prominent change in SAMP6 was the reduction of vertebral trabecular bone volume fraction (BV/TV) and trabecular BMD. Moderate decrease of trabecular bone mass was observed in the proximal tibia and distal femur. Increased marrow area and periosteal perimeter were investigated, though the cortical area and cortical thickness had no marked changes in the mid-tibial and mid-femoral cortical bones. These results indicate that bone microstructural properties in SAMP6 are remarkably heterogeneous throughout the skeleton, which is analogous to changes that occur in human bones. These findings further validate the relevance of SAMP6 as a model of senile osteoporosis.

In vivo assessment of the micro-structural properties of bone using high-resolution peripheral quantitative computed tomography (Hr-pQCT)

In vivo assessment of the micro-structural properties of bone using high-resolution peripheral quantitative computed tomography (Hr-pQCT)

Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS

AbstractRecent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean ± SEM age, 70.5 ± 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1α (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS.