Densitometric, morphometric and mechanical distributions in the human proximal femur

With the prevalent use of DXA-measured BMD to assess pathologic hip fractures and its recently reported lack of reliability to predict fracture or account for efficacy of anti-resorptive therapy, it is reasonable to assess whether variations in the primary and secondary tensile and compressive trabecular microstructure can account for variations in proximal femur strength in comparison to DXA-measured BMD. To that end, microstructural and densitometric measures of trabecular bone specimens, from discrete sites within the proximal femur, were correlated with their mechanical properties. We hypothesize that accounting for regional variations in trabecular microstructure will improve predictions of proximal femur strength and stiffness compared to bone density measured by DXA. Forty-seven samples (seven donors) from seven distinct sites of human proximal femur underwent DXA and muCT imaging and mechanical testing. The results revealed significant variations in BMC, morphometric indices and mechanical properties within the proximal femur. This work has demonstrated that the mechanical performance of each sub-region is highly dependent on the corresponding trabecular microstructure. BMD measured by DXA at standard regions of interest cannot resolve the variations in trabecular density and microstructure that govern the mechanical behavior of the proximal femur. This work suggests that a quantitative Singh index that uses high resolution QCT to monitor the trabecular microstructure at specific sub-regions of the proximal femur may allow better predictions of hip fracture risk in individual patients and an improved assessment of changing bone structure in response to pharmacological interventions.     

Laser-Supported Dual Energy X-Ray Absorptiometry (DXL) Compared to Conventional Absorptiometry (DXA) and to FRAX as Tools for Fracture Risk Assessments

Dual X-ray and Laser (DXL) adds a measure of the external thickness of the heel, measured by laser, to a conventional measurement of bone mineral density (BMD) of the calcaneus, using Dual energy X-ray Absorptiometry (DXA). The addition of heel thickness aims at a better separation of fatty tissue from bone than the standard method of DXA, which may mistake fatty tissue for bone and vice versa. The primary aim of this study was to evaluate whether DXL of the calcaneus can be used to assess the 10-year risk of fractures. Secondary aims were to compare the predictive ability of DXL with the two most established methods, Dual energy X-ray Absorptiometry (DXA) of the hip and spine and the WHO fracture risk assessment tool, FRAX. In 1999 a cohort of 388 elderly Swedish women (mean age 73.2 years) was examined with all three methods. Prospective fracture data was collected in 2010 from health care registers. One SD decrease in BMD of the heel resulted in an age-adjusted Hazard Ratio (HR) of 1.47 for a hip fracture (95% CI 1.09–1.98). Harrell’s C is the Cox regression counterpart of the Area Under Curve (AUC) of the Receiver Operating Characteristic (ROC) as a measure of predictive accuracy. Harrell’s C for BMD of the calcaneus was 0.65 for prediction of hip fractures. These results were not significantly different from those for BMD of the femoral neck or for FRAX. The HR for a hip fracture, for one SD decrease in BMD at the femoral neck, was 1.72 (95% CI 1.21–2.44. Harrell’s C was 0.67 for BMD at the femoral neck and 0.59 for FRAX. We conclude that DXL of the calcaneus could be a useful tool for fracture risk assessments.     

Prediction of femoral strength using 3D finite element models reconstructed from DXA images: validation against experiments

Computed tomography (CT)-based finite element (FE) models may improve the current osteoporosis diagnostics and prediction of fracture risk by providing an estimate for femoral strength. However, the need for a CT scan, as opposed to the conventional use of dual-energy X-ray absorptiometry (DXA) for osteoporosis diagnostics, is considered a major obstacle. The 3D shape and bone mineral density (BMD) distribution of a femur can be reconstructed using a statistical shape and appearance model (SSAM) and the DXA image of the femur. Then, the reconstructed shape and BMD could be used to build FE models to predict bone strength. Since high accuracy is needed in all steps of the analysis, this study aimed at evaluating the ability of a 3D FE model built from one 2D DXA image to predict the strains and fracture load of human femora. Three cadaver femora were retrieved, for which experimental measurements from ex vivo mechanical tests were available. FE models were built using the SSAM-based reconstructions: using only the SSAM-reconstructed shape, only the SSAM-reconstructed BMD distribution, and the full SSAM-based reconstruction (including both shape and BMD distribution). When compared with experimental data, the SSAM-based models predicted accurately principal strains (coefficient of determination >0.83, normalized root-mean-square error <16%) and femoral strength (standard error of the estimate 1215 N). These results were only slightly inferior to those obtained with CT-based FE models, but with the considerable advantage of the models being built from DXA images. In summary, the results support the feasibility of SSAM-based models as a practical tool to introduce FE-based bone strength estimation in the current fracture risk diagnostics.     

Estimation of 3D shape, internal density and mechanics of proximal femur by combining bone mineral density images with shape and density templates

Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) alone is only a moderate predictor of fracture risk. Finite element analysis (FEA) of bone mechanics, based on DXA images, may improve the prediction of fracture risk. We developed a method to estimate the 3D shape and density distribution of the proximal femur, using a 2D BMD image and a femur shape template. Proximal femurs of eighteen human cadavers were imaged using computed tomography and divided into two sets (N = 9 + 9). The template was created from the samples in first set by using 3D generalized Procrustes analysis and thin-plate splines. Subsequently, the template and 2D BMD image were utilized to estimate the shape and internal density distribution of the femurs in the second set. Finally, FEA was conducted based on the original and the estimated bone models to evaluate the effect of geometrical and density distributional errors on the mechanical strength. The volumetric errors induced by the estimation itself were low (<1.4%). In the estimation of bones in the second set, the mean distance difference between the estimated and the original bone surfaces was 0.80 ± 0.19 mm, suggesting feasible estimation of the femoral shape. The mean absolute error in voxel-by-voxel BMD was 120±8 mg cm?3. In FEA, the stiffness of the proximal femur differed by -7±16% between the original and estimated bones. The present method, in comparison with methods used in previous studies, improved the prediction of the geometry, the BMD distribution and the mechanical characteristics of the proximal femur. Potentially, the proposed method could ultimately improve the determination of bone fracture risk.     

How drugs decrease fracture risk: lessons from trials

In women with osteoporosis, each 1% improvement in spine BMD (by DXA) is expected to reduce vertebral fracture risk by about 4%. However, randomized trials of antiresorptive agents show that 1 to 6% improvements in spine BMD reduce vertebral fracture risk by 35 to 50%. Less 20% of the decreased spine fracture risk produced by alendronate or raloxifene be explained by improvement in spine BMD. The discrepancy is even greater during the first year or two of treatment when 1 to 4% improvements in BMD are associated with 65-68% decreases in spine fracture risk. Bisphosphonates continue to increase BMD but the reduction in fracture risk wanes to 20 to 45%. DXA underestimates the change in bone density of spinal trabecular bone and this might explain part of the discrepancy between expected and observed reductions in spine fracture risk. Even more accurate measurement of BMD would not explain the rapid onset and later waning of effect despite gradually increasing BMD. The biomechanical effects inhibiting bone resorption could explain the early onset but not the waning effectiveness. The waning effectiveness of antiresorptives raises concerns that prolonged inhibition of remodeling may weaken bone by allowing microdamage to accumulate. The effect of drugs on nonspine fracture risk is more complex and cannot be predicted from changes in DXA BMD. For example, Beck showed that long-term users of estrogen increase section modulus vs. nonusers with a net increase in section modulus and predicted femoral neck strength despite losing about 0.4% per year in femoral neck BMD. PTH reduces spine fracture risk and this effect is more completely explained by improvement in spine BMD. This suggests that sustaining the increased BMD produced by PTH may maintain long-term reductions in fracture risk.     

Biomarkers for osteoporosis management: utility in diagnosis, fracture risk prediction and therapy monitoring

Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in an increased risk of fracture. While the level of bone mass can be estimated by measuring bone mineral density (BMD) using dual X-ray absorptiometry (DXA), its measurement does not capture all the risk factors for fracture. Quantitative changes in skeletal turnover can be assessed easily and non-invasively by the measurement of serum and urinary biochemical markers; the most sensitive markers include serum osteocalcin, bone specific alkaline phosphatase, the N-terminal propeptide of type I collagen for bone formation, and the crosslinked C- (CTX) and N- (NTX) telopeptides of type I collagen for bone resorption. Advances in our knowledge of bone matrix biochemistry, most notably of post-translational modifications in type I collagen, are likely to lead to the development of new biochemical markers that reflect changes in the material property of bone, an important determinant of bone strength. Among those, the measurement of the urinary ratio of native (alpha) to isomerized (beta) CTX - an index of bone matrix maturation - has been shown to be predictive of fracture risk independently of BMD and bone turnover.In postmenopausal osteoporosis, levels of bone resorption markers above the upper limit of the premenopausal range are associated with an increased risk of hip, vertebral, and nonvertebral fracture, independent of BMD. Therefore, the combined use of BMD measurement and biochemical markers is helpful in risk assessment, especially in those women who are not identified as at risk by BMD measurement alone. Levels of bone markers decrease rapidly with antiresorptive therapies, and the levels reached after 3-6 months of therapy have been shown to be more strongly associated with fracture outcome than changes in BMD. Preliminary studies indicate that monitoring changes of bone formation markers could also be useful to monitor anabolic therapies, including intermittent parathyroid hormone administration and, possibly, to improve adherence to treatment. Thus, repeated measurements of bone markers during therapy may help improve the management of osteoporosis in patients.     

Urban-Rural Differences in Bone Mineral Density: A Cross Sectional Analysis Based on the Hyderabad Indian Migration Study

Background

Fracture risk is rising in countries undergoing rapid rural to urban migration, but whether this reflects an adverse effect of urbanization on intrinsic bone strength, as reflected by bone mineral density (BMD), is currently unknown.

Methods

Lumbar spine (LS) and total hip (TH) BMD, and total body fat and lean mass, were obtained from DXA scans performed in the Hyderabad arm of the Indian Migration Study (54% male, mean age 49 years). Sib-pair comparisons were performed between rural-urban migrants (RUM) and rural non-migrated (RNM) siblings (N = 185 sib-pairs).

Results

In analyses adjusted for height, gender, age and occupation, rural to urban migration was associated with higher lumbar and hip BMD and greater predicted hip strength; ΔLS BMD 0.030 (0.005, 0.055) g/cm², ΔTH BMD 0.044 (0.024; 0.064) g/cm², Δcross-sectional moment of inertia 0.162 (0.036, 0.289) cm⁴. These differences were largely attenuated after adjusting for body composition, insulin levels and current lifestyle factors ie. years of smoking, alcohol consumption and moderate to vigorous physical activity. Further analyses suggested that differences in lean mass, and to a lesser extent fat mass, largely explained the BMD differences which we observed.

Conclusions

Rural to urban migration as an adult is associated with higher BMD and greater predicted hip strength, reflecting associated alterations in body composition. It remains to be seen how differences in BMD between migration groups will translate into fracture risk in becoming years.     

Contribution of bone mineral density and bone turnover markers to the estimation of risk of osteoporotic fracture in postmenopausal women

In osteoporosis, the main cause for concern is the increase in the risk of fractures. The level of bone mineral density (BMD) measured by various techniques has been shown to be a strong predictor of fracture risk in postmenopausal women. However, half of patients with incident fractures have BMD value above the diagnostic threshold of osteoporosis defined as a T-score of -2.5 SD or more below the average value of young healthy women. Clearly there is a need for improvement in the identification of patients at risk for fracture. Several prospective studies have shown that an increased bone resorption evaluated by specific biochemical markers was associated with increased risk of the hip, spine and non-vertebral fractures independently of BMD. The use of bone markers in individual patients may be appropriate in some situations, especially in women who are not detected at risk by BMD measurements. For example, in the OFELY study including 668 postmenopausal women followed prospectively over 9 years, we found that among the 115 incident fractures, 54 (47%) actually occurred in non-osteoporotic women. Among these women, the combination of bone markers and history of previous fracture was highly predictive of fracture risk. Thus, bone markers may be used in the assessment of fracture risk in selected cases in which BMD and clinical risk factors are not enough to take a treatment decision. Advances in our knowledge of bone matrix biochemistry, most notably of post-translational modifications in type I collagen, may allow identification of biochemical markers that reflect changes in the material property of bone, which is an important determinant of bone strength. Preliminary in vitro studies indicate that the extent of post-translational modifications of collagen--which can be reflected in vivo by the measurement of the urinary ratio between native and isomerised type I collagen--play a role in determining the mechanical competence of cortical bone, independently of BMD. Further studies in osteoporosis should explore the changes in these biochemical parameters of bone matrix as they may represent a key component of bone quality.     

In-Vivo Assessment of Femoral Bone Strength Using Finite Element Analysis (FEA) Based on Routine MDCT Imaging: A Preliminary Study on Patients with Vertebral Fractures

PurposeTo experimentally validate a non-linear finite element analysis (FEA) modeling approach assessing in-vitro fracture risk at the proximal femur and to transfer the method to standard in-vivo multi-detector computed tomography (MDCT) data of the hip aiming to predict additional hip fracture risk in subjects with and without osteoporosis associated vertebral fractures using bone mineral density (BMD) measurements as gold standard.MethodsOne fresh-frozen human femur specimen was mechanically tested and fractured simulating stance and clinically relevant fall loading configurations to the hip. After experimental in-vitro validation, the FEA simulation protocol was transferred to standard contrast-enhanced in-vivo MDCT images to calculate individual hip fracture risk each for 4 subjects with and without a history of osteoporotic vertebral fractures matched by age and gender. In addition, FEA based risk factor calculations were compared to manual femoral BMD measurements of all subjects.ResultsIn-vitro simulations showed good correlation with the experimentally measured strains both in stance (R² = 0.963) and fall configuration (R² = 0.976). The simulated maximum stress overestimated the experimental failure load (4743 N) by 14.7% (5440 N) while the simulated maximum strain overestimated by 4.7% (4968 N). The simulated failed elements coincided precisely with the experimentally determined fracture locations. BMD measurements in subjects with a history of osteoporotic vertebral fractures did not differ significantly from subjects without fragility fractures (femoral head: p = 0.989; femoral neck: p = 0.366), but showed higher FEA based risk factors for additional incident hip fractures (p = 0.028).ConclusionFEA simulations were successfully validated by elastic and destructive in-vitro experiments. In the subsequent in-vivo analyses, MDCT based FEA based risk factor differences for additional hip fractures were not mirrored by according BMD measurements. Our data suggests, that MDCT derived FEA models may assess bone strength more accurately than BMD measurements alone, providing a valuable in-vivo fracture risk assessment tool.     

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.     

Beyond Dxa: Advances in Clinical Applications of New Bone Imaging Technology

Dual-energy X-ray absorptiometry (DXA) is generally a very useful tool for assessing bone mineral density (BMD) and fracture risk. However, observational studies have shown that in certain instances, BMD as measured by DXA systematically over- or underestimates fracture risk. We herein describe the clinical conundrums encountered when assessing fracture risk by DXA in patients with primary hyperparathyroidism or type 2 diabetes and those of Chinese ethnicity. Furthermore, we discuss how advanced imaging technology that examines skeletal microarchitecture is furthering our understanding of fracture risk in these clinical situations.Abbreviations:BMD = bone mineral densityBMI = body mass indexBMS = bone material strengthBMT = bone microindentation testing3D = 3-dimensionalDM2 = type 2 diabetes mellitusDXA = dual-energy X-ray absorptiometryμFEA = microstructural finite element analysisFRAX = fracture risk assessment toolHRpQCT = high-resolution peripheral quantitative computed tomographyID = indentation distanceIDI = indentation distance increaseITS = individual trabecular segmentationPHPT = primary hyperparathyroidismPTH = parathyroid hormoneTBS = trabecular bone score     

Assessment of the 3-D shape and mechanics of the proximal femur using a shape template and a bone mineral density image

Measurement of bone mineral density (BMD) by DXA (dual-energy X-ray absorptiometry) is generally considered to be the clinical golden standard technique to diagnose osteoporosis. However, BMD alone is only a moderate predictor of fracture risk. Finite element analyses of bone mechanics can contribute to a more accurate prediction of fracture risk. In this study, we applied a method to estimate the 3D geometrical shape of bone based on a 2D BMD image and a femur shape template. Proximal femurs of eighteen human cadavers were imaged with computed tomography (CT) and divided into two groups. Image data from the first group (N = 9) were applied to create a shape template by using the general Procrustes analysis and thin plate splines. This template was then applied to estimate the shape of the femurs in the second group (N = 9), using the 2D BMD image projected from the CT image, and the geometrical errors of the shape estimation method were evaluated. Finally, finite element analysis with stance loading condition was conducted based on the original CT and the estimated geometrical shape to evaluate the effect of the geometrical errors on the outcome of the simulations. The volumetric errors induced by the shape estimation method itself were low (<0.6%). Increasing the number of bone specimens used for the template decreased the geometrical errors. When nine bones were used for the template, the mean distance difference (±SD) between the estimated and the CT shape surfaces was 1.2 ± 0.3 mm, indicating that the method was feasible for estimating the shape of the proximal femur. Small errors in geometry led systematically to larger errors in the mechanical simulations. The method could provide more information of the mechanical characteristics of bone based on 2D BMD radiography and could ultimately lead to more sensitive diagnosis of osteoporosis.     

The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats

Background

Activation of peroxisome proliferator-activated receptor (PPAR)gamma is associated with bone loss and increased fracture risk, while PPARalpha activation seems to have positive skeletal effects. To further explore these effects we have examined the effect of the PPARalpha agonists fenofibrate and Wyeth 14643, and the PPARgamma agonist pioglitazone, on bone mineral density (BMD), bone architecture and biomechanical strength in ovariectomized rats.

Methods

Fifty-five female Sprague-Dawley rats were assigned to five groups. One group was sham-operated and given vehicle (methylcellulose), the other groups were ovariectomized and given vehicle, fenofibrate, Wyeth 14643 and pioglitazone, respectively, daily for four months. Whole body and femoral BMD were measured by dual X-ray absorptiometry (DXA), and biomechanical testing of femurs, and micro-computed tomography (microCT) of the femoral shaft and head, were performed.

Results

Whole body and femoral BMD were significantly higher in sham controls and ovariectomized animals given fenofibrate, compared to ovariectomized controls. Ovariectomized rats given Wyeth 14643, maintained whole body BMD at sham levels, while rats on pioglitazone had lower whole body and femoral BMD, impaired bone quality and less mechanical strength compared to sham and ovariectomized controls. In contrast, cortical volume, trabecular bone volume and thickness, and endocortical volume were maintained at sham levels in rats given fenofibrate.

Conclusions

The PPARalpha agonist fenofibrate, and to a lesser extent the PPARaplha agonist Wyeth 14643, maintained BMD and bone architecture at sham levels, while the PPARgamma agonist pioglitazone exaggerated bone loss and negatively affected bone architecture, in ovariectomized rats.     

Epistasis between QTLs for bone density variation in Copenhagen × dark agouti F2 rats

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation.     

Near‐infrared bone densitometry: A feasibility study on distal radius measurement

Osteoporosis, defined as decreased bone mineral density (BMD), poses patients in dangers for fracture risk and has become a major public health problem worldwide because of is associated morbidity, mortality and costs. Without doubt, early detection and timely intervention are important to successfully manage osteoporosis and its associated complications. The dual‐energy x‐ray absorptiometry (DXA) is the most popular and standard method to measure BMD. However, limitations including radiation exposure and availability restrict its application for osteoporosis screening among general population. In this study, we developed a simple method to detect human distal radius bone density based on near infrared (NIR) image system. Among 10 volunteers (including 5 young and 5 elderly participants) receiving bone density measurement using our NIR image system at the ultradistal part of bilateral distal radius, we demonstrated a strong correlation between the optical attenuation and BMD measured with DXA, which may facilitate predicting bone density status. We hope our potential NIR image system may open a new avenue for development of osteoporosis screening facilities and help in prevention of osteoporosis related fracture and its associated complications in the near future. Pearson's correlations between BMD values from the DXA and light intensity of NIR system.      

The Lichfield bone study: the skeletal response to exercise in healthy young men

The skeletal response to short-term exercise training remains poorly described. We thus studied the lower limb skeletal response of 723 Caucasian male army recruits to a 12-wk training regime. Femoral bone volume was assessed using magnetic resonance imaging, bone ultrastructure by quantitative ultrasound (QUS), and bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) of the hip. Left hip BMD increased with training (mean ± SD: 0.85 ± 3.24, 2.93 ± 4.85, and 1.89 ± 2.85% for femoral neck, Ward's area, and total hip, respectively; all P < 0.001). Left calcaneal broadband ultrasound attenuation rose 3.57 ± 0.5% (P < 0.001), and left and right femoral cortical volume by 1.09 ± 4.05 and 0.71 ± 4.05%, respectively (P = 0.0001 and 0.003), largely through the rise in periosteal volume (0.78 ± 3.14 and 0.59 ± 2.58% for right and left, respectively, P < 0.001) with endosteal volumes unchanged. Before training, DXA and QUS measures were independent of limb dominance. However, the dominant femur had higher periosteal (25,991.49 vs. 2,5572 mm(3), P < 0.001), endosteal (6,063.33 vs. 5,983.12 mm(3), P = 0.001), and cortical volumes (19,928 vs. 19,589.56 mm(3), P = 0.001). Changes in DXA, QUS, and magnetic resonance imaging measures were independent of limb dominance. We show, for the first time, that short-term exercise training in young men is associated not only with a rise in human femoral BMD, but also in femoral bone volume, the latter largely through a periosteal response.     

Bone mineral density correlates with fracture load in experimental side impacts of the pelvis

Pelvic fractures resulting from automotive side impacts are associated with high mortality and morbidity, as well as substantial economic costs. Previous experimental studies have produced varying results regarding the tolerance of the pelvis to lateral force and compression. While bone mineral density (BMD) has been shown to correlate with fracture loads in the proximal femur, no such correlation has been established for the pelvis. Presently, we studied the relationships between total hip BMD and impact response parameters in lateral impacts of twelve isolated human pelves. The results indicated that total hip BMD significantly correlated with fracture force, Fmax, and maximum ring compression, Cmax, of the fractured pelves. These findings are evidence that BMD may be useful in assessing the risk of pelvic fracture in automotive side impacts. Poor correlation was observed between total hip BMD and maximum viscous response, (VC)max, energy at fracture, Epeak, and time to fracture, tpeak. Mean Fmax and calculated tolerances for Cmax and (VC)max were lower than those established in previous studies using full cadavers, likely a result of our removal of soft tissues from the pelves prior to impact.     

Parathyroid hormone gene with bone phenotypes in Chinese

Osteoporosis is a common disorder afflicting old people. The parathyroid hormone (PTH) gene is involved in bone remodeling and calcium homeostasis, and has been considered as an important candidate gene for osteoporosis. In this study, we simultaneously tested linkage and/or association of PTH gene with bone mineral density (BMD) and bone mineral content (BMC), two important risk factors for osteoporosis. A sample of 1263 subjects from 402 Chinese nuclear families was used. The families are composed of both parents and at least one healthy daughter aged from 20 to 45 years. All the subjects were genotyped at the polymorphic BstBI site inside the intron 2 of the PTH gene (a nucleotide substitution of G to A at the position +3244). BMD and BMC were measured at the lumbar spine and the hip region via dual-energy X-ray absorptiometry (DXA). Using QTDT (quantitative trait transmission disequilibrium test), we did not find significant results for association or linkage between the PTH gene and BMD or BMC variation at the spine or hip. Our data do not support the PTH gene as a quantitative trait locus (QTL) underlying the bone phenotypic variation in the Chinese population.     

Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment

Introduction

Osteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections.

Methods

Methods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD).

Results

AS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase.

Conclusions

Osteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.     

Evaluation of trabecular mechanical and microstructural properties in human calcaneal bone of advanced age using mechanical testing, microCT, and DXA

Early detection of fracture risk is important for initiating treatment and improving outcomes from both physiologic and pathologic causes of bone loss. While bone mineral density (a quantity measure) has traditionally been used for this purpose, alternative structural imaging parameters (quality measures) are proposed to better predict bone's true mechanical properties. To further elucidate this, trabecular bone from cadaveric human calcanei were used to evaluate the interrelationship of mechanical and structural parameters using mechanical testing, dual energy X-ray absorptiometry (DXA) scanning, and micro computed tomography (microCT) imaging. Directional specific structural properties were assessed in three-dimensional (3-D) and correlated to mechanical testing and DXA. The results demonstrated that microCT-derived indices of bone quality (i.e., volume fraction and structural model index) are better than DXA-derived bone mineral density for the prediction of the mechanical parameters of bone (i.e., elastic modulus, yield stress, and ultimate stress). Diagnostically, this implies that future work on the early prediction of fracture risk should focus as much on bone quality as on quantity. Furthermore, the results of this study show that a loss of bone primarily affects the connectedness and overall number of trabeculae. Ultimate stress, however, is better correlated with trabecular number than thickness. As such, primary prevention of osteoporosis may be more important than later countermeasures for bone loss.