Assessment of vertebral wedge strength using cancellous textural properties derived from digital tomosynthesis and density properties from dual energy X-ray absorptiometry and high resolution computed tomography

The purpose of this study was to examine the potential of digital tomosynthesis (DTS) derived cancellous bone textural measures to predict vertebral strength under conditions simulating a wedge fracture. 40 vertebral bodies (T6, T8, T11, and L3 levels) from 5 male and 5 female cadaveric donors were utilized. The specimens were scanned using dual energy X-ray absorptiometry (DXA) and high resolution computed tomography (HRCT) to obtain measures of bone mineral density (BMD) and content (BMC), and DTS to obtain measures of bone texture. Using a custom loading apparatus designed to deliver a nonuniform displacement resulting in a wedge deformity similar to those observed clinically, the specimens were loaded to fracture and their fracture strength was recorded. Mixed model regressions were used to determine the associations between wedge strength and DTS derived textural variables, alone and in the presence of BMD or BMC information. DTS derived fractal, lacunarity and mean intercept length variables correlated with wedge strength, and individually explained up to 53% variability. DTS derived textural variables, notably fractal dimension and lacunarity, contributed to multiple regression models of wedge strength independently from BMC and BMD. The model from a scan orientation transverse to the spine axis and in the anterior-posterior view resulted in highest explanatory capability (R²_adj = 0.91), with a scan orientation parallel to the spine axis and in the lateral view offering an alternative (R²_adj = 0.88). In conclusion, DTS can be used to examine cancellous texture relevant to vertebral wedge strength, and potentially complement BMD in assessment of vertebral fracture risk.     

Fatigue creep damage at the cement–bone interface: An experimental and a micro-mechanical finite element study

The goal of this study was to quantify the micromechanics of the cement–bone interface under tensile fatigue loading using finite element analysis (FEA) and to understand the underlying mechanisms that play a role in the fatigue behavior of this interface. Laboratory cement–bone specimens were subjected to a tensile fatigue load, while local displacements and crack growth on the specimen's surface were monitored. FEA models were created from these specimens based upon micro-computed tomography data. To accurately model interfacial gaps at the interface between the bone and cement, a custom-written erosion algorithm was applied to the bone model. A fatigue load was simulated in the FEA models while monitoring the local displacements and crack propagation. The results showed the FEA models were able to capture the general experimental creep damage behavior and creep stages of the interface. Consistent with the experiments, the majority of the deformation took place at the contact interface. Additionally, the FEA models predicted fatigue crack patterns similar to experimental findings. Experimental surface cracks correlated moderately with FEA surface cracks (r²=0.43), but did not correlate with the simulated crack volume fraction (r²=0.06). Although there was no relationship between experimental surface cracks and experimental creep damage displacement (r²=0.07), there was a strong relationship between the FEA crack volume fraction and the FEA creep damage displacement (r²=0.76). This study shows the additional value of FEA of the cement–bone interface relative to experimental studies and can therefore be used to optimize its mechanical properties.     

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.     

The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone

The amount of microdamage in bone tissue impairs mechanical performance and may act as a stimulus for bone remodeling. Here we determine how loading mode (tension vs. compression) and microstructure (trabecular microarchitecture, local trabecular thickness, and presence of resorption cavities) influence the number and volume of microdamage sites generated in cancellous bone following a single overload. Twenty paired cylindrical specimens of human vertebral cancellous bone from 10 donors (47–78 years) were mechanically loaded to apparent yield in either compression or tension, and imaged in three dimensions for microarchitecture and microdamage (voxel size 0.7×0.7×5.0 μm³). We found that the overall proportion of damaged tissue was greater (p=0.01) for apparent tension loading (3.9±2.4%, mean±SD) than for apparent compression loading (1.9±1.3%). Individual microdamage sites generated in tension were larger in volume (p<0.001) but not more numerous (p=0.64) than sites in compression. For both loading modes, the proportion of damaged tissue varied more across donors than with bone volume fraction, traditional measures of microarchitecture (trabecular thickness, trabecular separation, etc.), apparent Young?s modulus, or strength. Microdamage tended to occur in regions of greater trabecular thickness but not near observable resorption cavities. Taken together, these findings indicate that, regardless of loading mode, accumulation of microdamage in cancellous bone after monotonic loading to yield is influenced by donor characteristics other than traditional measures of microarchitecture, suggesting a possible role for tissue material properties.     

Variability of tissue mineral density can determine physiological creep of human vertebral cancellous bone

Creep is a time-dependent viscoelastic deformation observed under a constant prolonged load. It has been indicated that progressive vertebral deformation due to creep may increase the risk of vertebral fracture in the long-term. The objective of this study was to examine the relationships of creep with trabecular architecture and tissue mineral density (TMD) parameters in human vertebral cancellous bone at a physiological static strain level. Architecture and TMD parameters of cancellous bone were analyzed using microcomputerized tomography (micro-CT) in specimens cored out of human vertebrae. Then, creep and residual strains of the specimens were measured after a two-hour physiological compressive constant static loading and unloading cycle. Creep developed (3877 ± 2158 με) resulting in substantial levels of non-recoverable post-creep residual strain (1797 ± 1391 με). A strong positive linear correlation was found between creep and residual strain (r = 0.94, p < 0.001). The current results showed that smaller thickness, larger surface area, greater connectivity of trabeculae, less mean tissue mineral density (TMD, represented by gray levels) and higher variability of TMD are associated with increasing logarithmic creep rate. The TMD variability (GL(COV)) was the strongest correlate of creep rate (r = 0.79, p < 0.001). This result suggests that TMD variability may be a useful parameter for estimating the long-term deformation of a whole vertebral body. The results further suggest that the changes in TMD variability resulting from bone remodeling are of importance and may provide an insight into the understanding of the mechanisms underlying progressive failure of vertebral bodies and development of a clinical fracture.     

Effects of mechanical loading patterns,bone graft,and proximity to periosteum on bone defect healing

The goal of this study is to elucidate whether mechanobiological factors, including mechanical loading patterns, presence of bone graft, and proximity to the periosteum, correlate to de novo tissue generation and healing in critical sized long bone defects, which are enveloped by periosteum in situ and are bridged at 16 weeks, in sheep femora. Quantitative histomorphometric measures of defect cross sections show that, along the axis least able to resist bending loads (minor centroidal axis, CA), bone laid down in the first two weeks after surgery exhibits more mineralization albeit less total area compared to bone along the axis most able to resist bending loads (major CA). Similarly, areas of the cross section along the minor CA show a higher degree of perfusion albeit less total area of perfusion compared to bone along the major CA. Furthermore, proximity to the periosteal niche, in conjunction with the presence of bone graft and predominant loading patterns, relates significantly to the radial distribution of early bone apposition and perfusion of bone at 16 weeks after surgery (linear regression with R²>0.80). In the absence of graft, early bone density is relatively evenly distributed in the defect zone, as is the intensity of perfused tissue. As measured by a steeper average slope in intensity of fluorochrome (new bone) distribution between the periosteum and the IM nail, the presence of bone graft retards initial bone formation in the defect zone and is associated with less evenly distributed tissue perfusion (steeper slope) persisting 16 weeks after surgery. Finally, although the mean area of bone resorption is not significantly different within or between groups defined by the presence of graft and/or mechanical loading patterns in the defect zone, the mean area of infilling resorption spaces is significantly higher in areas of the defect zone least able to resist bending (minor CA) but is not significantly related to the presence of bone graft. To our knowledge, the use of the major and minor centroidal axes to relate prevailing mechanical loading patterns to area and density of early bone generation in bone defects has not been reported prior to this study and may provide a new means to assess structure–function relationships in de novo bone generation and healing of bone defects.     

Hyperlipidemia affects multiscale structure and strength of murine femur

To improve bone strength prediction beyond limitations of assessment founded solely on the bone mineral component, we investigated the effect of hyperlipidemia, present in more than 40% of osteoporotic patients, on multiscale structure of murine bone. Our overarching purpose is to estimate bone strength accurately, to facilitate mitigating fracture morbidity and mortality in patients. Because (i) orientation of collagen type I affects, independently of degree of mineralization, cortical bone?s micro-structural strength; and, (ii) hyperlipidemia affects collagen orientation and μCT volumetric tissue mineral density (vTMD) in murine cortical bone, we have constructed the first multiscale finite element (mFE), mouse-specific femoral model to study the effect of collagen orientation and vTMD on strength in Ldlr^−/−, a mouse model of hyperlipidemia, and its control wild type, on either high fat diet or normal diet. Each µCT scan-based mFE model included either element-specific elastic orthotropic properties calculated from collagen orientation and vTMD (collagen-density model) by experimentally validated formulation, or usual element-specific elastic isotropic material properties dependent on vTMD-only (density-only model). We found that collagen orientation, assessed by circularly polarized light and confocal microscopies, and vTMD, differed among groups and that microindentation results strongly correlate with elastic modulus of collagen-density models (r²=0.85, p=10⁻⁵). Collagen-density models yielded (1) larger strains, and therefore lower strength, in simulations of 3-point bending and physiological loading; and (2) higher correlation between mFE-predicted strength and 3-point bending experimental strength, than density-only models. This novel method supports ongoing translational research to achieve the as yet elusive goal of accurate bone strength prediction.     

Histomorphometrical studies of vertebral bone condition in farmed rainbow trout,Oncorhynchus mykiss

A major problem for the fish farming industry is to find reliable indicators of bone condition that could help to prevent vertebral abnormalities. Here, we summarize the main results of two recent studies aiming to assess the variation of two vertebral bone variables (bone mineralization and vertebral total bone area) during rainbow trout grow‐out in several French farms. We provide evidence for a wide range of variation for these parameters and for the occurrence of vertebral bone abnormalities, and new data on vertebral structure in trout reared either in various fish farms (influence of rearing conditions) or at different temperatures (influence of various growth rates). Although further experiments are needed to understand bone metabolism in trout, these findings increase our knowledge on growth and modelling of vertebrae, and provide valuable data that will enable comparisons in the future.     

经皮椎体成形术治疗骨质疏松性椎体压缩骨折的临床疗效及术后邻近椎体骨折的危险因素分析

摘要 目的：观察骨质疏松性椎体压缩骨折（OVCFs）患者以经皮椎体成形术（PVP）治疗后的临床疗效,并分析术后邻近椎体骨折的危险因素。方法：选取我院2018年6月~2020年9月期间收治的OVCFs患者180例,给予PVP治疗,观察其治疗效果、骨水泥渗漏情况、术后邻近椎体骨折发生情况,采用单因素及多因素Logistic回归分析术后邻近椎体骨折的危险因素。结果：OVCFs患者术前~术后6个月功能障碍指数（ODI）、疼痛视觉模拟评分（VAS）、活动能力评分（LAS）均呈降低趋势（P＜0.05）。随访期间,180例患者中,15例（8.33%）出现了骨水泥渗漏,但均不需要进一步处理。32例（17.78%）出现了术后邻近椎体骨折,148例未出现术后邻近椎体骨折,并以此进行分组。再骨折组、未再骨折组在年龄、骨折病史、骨密度、Cobb角、椎体高度恢复、骨水泥渗漏情况、使用抗骨质疏松药物方面对比有明显差异（P<0.05）。年龄>70岁、骨水泥渗漏、骨密度<-2.5SD、未使用抗骨质疏松药物、Cobb角<15°、椎体高度恢复率>87%均是PVP术后邻近椎体骨折的危险因素（P<0.05）。结论：PVP治疗OVCFs疗效较好,可缓解患者疼痛、减轻功能障碍、改善活动能力,术后邻近椎体骨折的发生受年龄、骨密度、Cobb角等多种因素影响,临床可针对这些因素给予对应的干预措施。     

A primary phosphorus‐deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization

To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post‐smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro‐anatomical level. Animals that received the P‐deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X‐ray‐based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency‐related malformations in farmed S. salar.     

Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification

Lysphosphatidic acid (LPA) is a major natural bioactive lipid mediator whose biological functions affect multiple organs. These include bone as demonstrated by global Lpar1-knockout mice (Lpar1^−/−) which present a bone growth defect. LPA acts on all bone cells including osteoblasts, that are responsible for bone formation, and osteoclasts, which are specialized cells that resorb bone. LPA appears as a potential new coupling molecule during bone remodeling. LPA₁ is the most ubiquitous LPA receptor among the six LPA receptor family members (LPA_1–6). To better understand the specific role of LPA via its receptor LPA₁ in osteoblastic cell lineage we generated osteoblast-specific Lpar1 knockout mice (Lpar1-∆Ob) by crossing Lpar1^flox/flox and Osx:Cre⁺ mouse lines. Lpar1-∆Ob mice do not recapitulate the bone defects of Lpar1^−/− mice but revealed reduced bone mineralization and decreased cortical thickness, as well as increased bone porosity associated with an augmentation in the lacunae areas of osteocyte and their apoptotic yield. In vitro, primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1^−/− osteoblasts revealed a remarkable premature expression of alkaline phosphatase, reduced cell proliferation associated with decreased YAP-P nuclear accumulation, and reduced mineralization activity. Osteocyte specification is markedly impaired as demonstrated by reduced expression of early (E11) and late (DMP1, DKK1, SOST) osteocyte markers ex vivo in enriched osteocytic fractions of Lpar1-∆Ob mouse bone explants. In addition, E11 expression and dendrite formation induced by FGF2 are markedly impaired in both primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1^−/− osteoblasts. Taken together these results suggest a new role for LPA in bone mass control via bone mineralization and osteocyte function.     

Bone Mineral Density in Pituitary Stalk Interruption Syndrome: The Role of Insulin-Like Growth Factor-1 and Testosterone at Different Skeletal Sites

ObjectiveThis study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT).MethodsMale patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites.ResultsFifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009).ConclusionCollectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non–recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.     

Micro-CT and micro-FE analysis of pedicle screw fixation under different loading conditions

Anchorage of pedicle screw instrumentation in the elderly spine with poor bone quality remains challenging. In this study, micro finite element (µFE) models were used to assess the specific influence of screw design and the relative contribution of local bone density to fixation mechanics. These were created from micro computer tomography (µCT) scans of vertebras implanted with two types of pedicle screws, including a full region-or-interest of 10 mm radius around each screw, as well as submodels for the pedicle and inner trabecular bone of the vertebral body. The local bone volume fraction (BV/TV) calculated from the µCT scans around different regions of the screw (pedicle, inner trabecular region of the vertebral body) were then related to the predicted stiffness in simulated pull-out tests as well as to the experimental pull-out and torsional fixation properties mechanically measured on the corresponding specimens. Results show that predicted stiffness correlated excellently with experimental pull-out strength (R² > 0.92, p < .043), better than regional BV/TV alone (R2 = 0.79, p = .003). They also show that correlations between fixation properties and BV/TV were increased when accounting only for the pedicle zone (R² = 0.66–0.94, p ≤ .032), but with weaker correlations for torsional loads (R² < 0.10). Our analyses highlight the role of local density in the pedicle zone on the fixation stiffness and strength of pedicle screws when pull-out loads are involved, but that local apparent bone density alone may not be sufficient to explain resistance in torsion.     

A patient-specific computer tomography-based finite element methodology to calculate the six dimensional stiffness matrix of human vertebral bodies

In most finite element (FE) studies of vertebral bodies, axial compression is the loading mode of choice to investigate structural properties, but this might not adequately reflect the various loads to which the spine is subjected during daily activities or the increased fracture risk associated with shearing or bending loads. This work aims at proposing a patient-specific computer tomography (CT)-based methodology, using the currently most advanced, clinically applicable finite element approach to perform a structural investigation of the vertebral body by calculation of its full six dimensional (6D) stiffness matrix. FE models were created from voxel images after smoothing of the peripheral voxels and extrusion of a cortical shell, with material laws describing heterogeneous, anisotropic elasticity for trabecular bone, isotropic elasticity for the cortex based on experimental data. Validated against experimental axial stiffness, these models were loaded in the six canonical modes and their 6D stiffness matrix calculated. Results show that, on average, the major vertebral rigidities correlated well or excellently with the axial rigidity but that weaker correlations were observed for the minor coupling rigidities and for the image-based density measurements. This suggests that axial rigidity is representative of the overall stiffness of the vertebral body and that finite element analysis brings more insight in vertebral fragility than densitometric approaches. Finally, this extended patient-specific FE methodology provides a more complete quantification of structural properties for clinical studies at the spine.     

Finite element analyses of human vertebral bodies embedded in polymethylmethalcrylate or loaded via the hyperelastic intervertebral disc models provide equivalent predictions of experimental strength

Quantitative computer tomography (QCT)-based finite element (FE) models of vertebral body provide better prediction of vertebral strength than dual energy X-ray absorptiometry. However, most models were validated against compression of vertebral bodies with endplates embedded in polymethylmethalcrylate (PMMA). Yet, loading being as important as bone density, the absence of intervertebral disc (IVD) affects the strength. Accordingly, the aim was to assess the strength predictions of the classic FE models (vertebral body embedded) against the in vitro and in silico strengths of vertebral bodies loaded via IVDs. High resolution peripheral QCT (HR-pQCT) were performed on 13 segments (T11/T12/L1). T11 and L1 were augmented with PMMA and the samples were tested under a 4° wedge compression until failure of T12. Specimen-specific model was generated for each T12 from the HR-pQCT data. Two FE sets were created: FE-PMMA refers to the classical vertebral body embedded model under axial compression; FE-IVD to their loading via hyperelastic IVD model under the wedge compression as conducted experimentally. Results showed that FE-PMMA models overestimated the experimental strength and their strength prediction was satisfactory considering the different experimental set-up. On the other hand, the FE-IVD models did not prove significantly better (Exp/FE-PMMA: R²=0.68; Exp/FE-IVD: R²=0.71, p=0.84). In conclusion, FE-PMMA correlates well with in vitro strength of human vertebral bodies loaded via real IVDs and FE-IVD with hyperelastic IVDs do not significantly improve this correlation. Therefore, it seems not worth adding the IVDs to vertebral body models until fully validated patient-specific IVD models become available.     

Contribution of vertebral [corrected] bodies, endplates, and intervertebral discs to the compression creep of spinal motion segments

Spinal segments show non-linear behavior under axial compression. It is unclear to what extent this behavior is attributable to the different components of the segment. In this study, we quantified the separate contributions of vertebral bodies and intervertebral discs to creep of a segment. Secondly, we investigated the contribution of bone and osteochondral endplate (endplates including cartilage) to the deformation of the vertebral body. From eight porcine spines a motion segment, a disc and a vertebral body were dissected and subjected to mechanical testing. In an additional test, cylindrical samples, machined from the lowest thoracic vertebrae of 11 porcine spines, were used to compare the deformation of vertebral bone and endplate. All specimens were subjected to three loading cycles, each comprising a loading phase (2.0 MPa, 15 min) and a recovery phase (0.001 MPa, 30 min). All specimens displayed substantial time-dependent height changes. Average creep was the largest in motion segments and smallest in vertebral bodies. Bone samples with endplates displayed substantially more creep than samples without. In the early phase, behavior of the vertebra was similar to that of the disc. Visco-elastic deformation of the endplate therefore appeared dominant. In the late creep phase, behavior of the segment was similar to that of isolated discs, suggesting that in this phase the disc dominated creep behavior, possibly by fluid flow from the nucleus. We conclude that creep deformation of vertebral bodies contributes substantially to creep of motion segments and that within a vertebral body endplates play a major role.     

Discordance between Prevalent Vertebral Fracture and Vertebral Strength Estimated by the Finite Element Method Based on Quantitative Computed Tomography in Patients with Type 2 Diabetes Mellitus

Background

Bone fragility is increased in patients with type 2 diabetes mellitus (T2DM), but a useful method to estimate bone fragility in T2DM patients is lacking because bone mineral density alone is not sufficient to assess the risk of fracture. This study investigated the association between prevalent vertebral fractures (VFs) and the vertebral strength index estimated by the quantitative computed tomography-based nonlinear finite element method (QCT-based nonlinear FEM) using multi-detector computed tomography (MDCT) for clinical practice use.

Research Design and Methods

A cross-sectional observational study was conducted on 54 postmenopausal women and 92 men over 50 years of age, all of whom had T2DM. The vertebral strength index was compared in patients with and without VFs confirmed by spinal radiographs. A standard FEM procedure was performed with the application of known parameters for the bone material properties obtained from nondiabetic subjects.

Results

A total of 20 women (37.0%) and 39 men (42.4%) with VFs were identified. The vertebral strength index was significantly higher in the men than in the women (P<0.01). Multiple regression analysis demonstrated that the vertebral strength index was significantly and positively correlated with the spinal bone mineral density (BMD) and inversely associated with age in both genders. There were no significant differences in the parameters, including the vertebral strength index, between patients with and without VFs. Logistic regression analysis adjusted for age, spine BMD, BMI, HbA1c, and duration of T2DM did not indicate a significant relationship between the vertebral strength index and the presence of VFs.

Conclusion

The vertebral strength index calculated by QCT-based nonlinear FEM using material property parameters obtained from nondiabetic subjects, whose risk of fracture is lower than that of T2DM patients, was not significantly associated with bone fragility in patients with T2DM. This discordance may indirectly suggest that patients with T2DM have deteriorated bone material compared with nondiabetic subjects, a potential cause of bone fragility in T2DM patients.     

GPRC6A Null Mice Exhibit Osteopenia,Feminization and Metabolic Syndrome

Background

GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown.

Methods/Principal Findings

In this study, we created and characterized the phenotype of GPRC6A ^−/− mice. We observed complex metabolic abnormalities in GPRC6A ^−/− mice involving multiple organ systems that express GPRC6A, including bone, kidney, testes, and liver. GPRC6A ^−/− mice exhibited hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance. In addition, we observed high expression of GPRC6A in Leydig cells in the testis. Ablation of GPRC6A resulted in feminization of male GPRC6A ^−/− mice in association with decreased lean body mass, increased fat mass, increased circulating levels of estradiol, and reduced levels of testosterone. GPRC6A was also highly expressed in kidney proximal and distal tubules, and GPRC6A^−/− mice exhibited increments in urine Ca/Cr and PO₄/Cr ratios as well as low molecular weight proteinuria. Finally, GPRC6A ^−/− mice exhibited a decrease in bone mineral density (BMD) in association with impaired mineralization of bone.

Conclusions/Significance

GPRC6A^−/− mice have a metabolic syndrome characterized by defective osteoblast-mediated bone mineralization, abnormal renal handling of calcium and phosphorus, fatty liver, glucose intolerance and disordered steroidogenesis. These findings suggest the overall function of GPRC6A may be to coordinate the anabolic responses of multiple tissues through the sensing of extracellular amino acids, osteocalcin and divalent cations.     

Quantitative associations between osteocyte density and biomechanics, microcrack and microstructure in OVX rats vertebral trabeculae

Osteocytes actively regulate bone modeling and remodeling, direct skeletal mineralization, and regulate calcium/phosphate homeostasis and extracellular matrix metabolism; yet the specific role of osteocytes in maintaining bone structural integrity and strength is unknown. Studies have shown that the density of osteocytes decreases with age and estrogen deficiency, as seen in postmenopausal women. Here, we examined the relationships between osteocyte density and the related variables, including biomechanics, bone mineral density, microcrack and microstructure of vertebral trabeculae, in ovariectomized rats. We found that osteocyte density correlated with some of the parameters that determine the biomechanical quality of bone. Our findings suggest that osteocytes could play a crucial role in maintaining the mechanical quality of bone, and osteocyte density could be considered as an alternative index in assessing bone quality.     

Effect of ring width, cambial age, and climatic variables on the within-ring wood density profile of Norway spruce Picea abies (L.) Karst.

Studying the effects of dendrometric and climatic variables on within-ring density variations needs flexible and interpretable models. We described the within-ring density profile using a piecewise linear regression and studied its dependence on (1) dendrometric variables such as cambial age (CA) and ring width (RW), and (2) climatic variables. Based on X-ray analysis of 5,191 Norway spruce rings, a six-parameter three-segmented model was fitted on each within-ring density profile. Each model parameter was related to dendrometric and climatic variables using multiple linear regressions. Then, these models were assembled in two models relating the within-ring density profile to (1) RW and CA (model M1), and (2) climatic variables (model M2). M1 showed an R ² of 83.4 % and a residual standard error of 68.5 kg m^?3. Larger rings were associated with a decrease of latewood proportion and mean ring density. Rings with high CA were characterised by high maximum ring density. M2 showed an R ² of 60.9 % and a residual standard error of 94.9 kg m^?3. Warm summers increased the maximum ring density. Years with favourable water status decreased mean ring density. The piecewise linear models allowed the classification of within-ring density profiles in three types. Considering CA and RW led to the most explicative model since RW described many processes such as silviculture or climate. Earlywood density was impacted by water status while latewood density was conditioned by both temperatures and water status. Our approach may be used for the identification of within-ring density fluctuations or to assess the effects of silviculture or global change on the within-ring density profile.