Objectives. The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity. Methods. A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings. Results. For the whole sample, BUA predicted 29% of the study population variance in whole body BMC and BMD, 23% to 24% of the study population variance in lumbar spine BMC and BMD, and 21% to 24% of the variance in femoral neck BMC and BMD (p < 0.001). BUA predictions were strongest for the most mature participants (pre-APHV R. 2. = 0.03 to 0.19; peri-APHV R. 2. = 0.05 to 0.17; post-APHV R. 2. = 0.18 to 0.28) and marginally stronger for girls (R. 2. = 0.25-0.32, p < 0.001) than for boys (R. 2. = 0.21-0.27, p < 0.001). Agreement in quartile rankings between QUS and DXA measures of bone mass was generally poor (27.3% to 38.2%). Conclusion. Calcaneal BUA has a weak to moderate relationship with DXA measurements of bone mass in children, and has a tendency to misclassify children on the basis of quartile rankings. Cite this article: B. K. Weeks, R. Hirsch, R. C. Nogueira, B. R. Beck. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Joint Res 2016;5:538–543. DOI: 10.1302/2046-3758.511.BJR-2016-0116.R1

Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women. Methods. RF signal and speed of sound (SOS) were obtained using an axial transmission QUS at one‐third distal radius for 246 postmenopausal women. Based on the involved RF signal, we conducted a MResNet, which combines multi-channel training with original ResNet, to classify the high risk of fragility fractures patients from all subjects. The bone mineral density (BMD) at lumber, hip and femoral neck acquired with DXA was recorded on the same day. The fracture history of all subjects in adulthood were collected. To assess the ability of the different methods in the discrimination of fragile fracture, the odds ratios (OR) calculated using binomial logistic regression analysis and the area under the receiver operator characteristic curves (AUC) were analyzed. Results. Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was discriminant for all fragile fractures (OR = 2.64; AUC = 0.74), for Vertebral fracture (OR = 3.02; AUC = 0.77), for non-vertebral fracture (OR = 2.01; AUC = 0.69). MResNet showed comparable performance to that of BMD of hip and lumbar with all types of fractures, and significantly better performance than SOS all types of fractures. Conclusions. the MResNet model based on the ultrasonic RF signal can significantly improve the ability of QUS device to recognize previous fragile fractures. Moreover, the performance of the proposed model modified by age, weight, and height is further optimized. These results open perspectives to evaluate the risk of fragile fracture applying a deep learning model to analyze ultrasonic RF signal

Introduction. Trabecular bone score (TBS) is a parameter of bone microarchitecture that is determined by the level analysis of DXA images. TBS is associated with fractures in the preliminary case-control and prospective studies. The aim of this study was to assess the TBS role in the traumatology and orthopedics. Materials and methods. We've examined 176 healthy women aged 40–79 years (mean age – 53.4±0.6 yrs) and 117 men aged 40–79 years (mean age – 59.8±0.9 yrs). Bone mineral density (BMD) of whole body, PA lumbar spine and proximal femur were measured by DXA method (Prodigy, GEHC Lunar, Madison, WI, USA) and PA spine TBS were assessed by TBS iNsight® software package installed on the available DXA machine (Med-Imaps, Pessac, France). Results. We have observed a significant decrease of TBS as a function of age (F=6.56; p=0.0003) whereas PA spine BMD was significantly increasing with age (F=4.04; p=0.008) in the examined women. This contradiction can be traced to the spinal osteoarthritis and degenerative diseases progressing with age in the elderly patients. TBS was significantly lower in women with duration of PMP over 4 yrs (p=0.003) in comparison with women without menopause; BMD of spine significantly decreased in women with duration of PMP over 7–9 yrs (p=0.02). So, the TBS can detect changes in the state of bone tissue at the earlier stage than BMD. We have observed a significant decrease of TBS in men with ageing (F=2.44; p=0.05). Overall TBS values in men are lower than the age matched TBS values in women. Conclusion. TBS is an independent parameter which has a potential diagnostic value of its own, without taking into account the BMD results. The study concerning patients with osteoporosis and fractures is underway

Objectives. To assess the sensitivity and specificity of self-reported osteoporosis compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis, and to describe medication use among participants with the condition. Methods. Data were obtained from a population-based longitudinal study and assessed for the prevalence of osteoporosis, falls, fractures and medication use. DXA scans were also undertaken. Results. Overall 3.8% (95% confidence interval (CI) 3.2 to 4.5) of respondents and 8.8% (95% CI 7.5 to 10.3) of those aged ≥ 50 years reported that they had been diagnosed with osteoporosis by a doctor. The sensitivity (those self-reporting osteoporosis and having low bone mineral density (BMD) on DXA) was low (22.7%), although the specificity was high (94.4%). Only 16.1% of those aged ≥ 50 years and with DXA-defined osteoporosis were taking bisphosphonates. Conclusions. The sensitivity of self-reporting to identify osteoporosis is low. Anti-osteoporotic medications are an important part of osteoporosis treatment but opportunities to use appropriate medications were missed and inappropriate medications were used

Introduction. Precision error (PE) in Dual Energy X-Ray Absorptiometry (DXA) is important for accurate monitoring of changes in Bone-Mineral-Density (BMD). It has been demonstrated that BMD PE increases with increasing BMI. In vivo PE for the Trabecular-Bone-Score (TBS) has not been reported. This study aimed to evaluate the short-term PE (STPE)) of BMD and TBS and to investigate the effect of obesity on DXA PE. Method. DXA lumbar spine scans (L1–L4) were performed using GE Lunar Prodigy. STPE was measured in 91 women (Group A) at a single visit by duplicating scans with repositioning in-between. PE was calculated as the percentage coefficient of variation (%CV). Group A was sub-divided into four groups based on BMI (A.1. <25kg/m2, A.2. 25–29.9kg/m2, A.3. 30–35kg/m2 and A.4. >35kg/m2) to assess the effect of obesity on STPE. Abnormally different vertebrae were excluded from the analysis in accordance with The International Society for Clinical Densitometry (ISCD) recommendations. Results. The Group A STPE was 1.26 % for BMD and 2.04% for TBS. Short-term PE for BMD and TBS respectively in the BMI subgroups was: A.1. 1.07% and 1.82%, A.2. 1.34% and 2.26%, A.3. 1.25% and 2.35%, A.4. 1.68% and 1.82%. Conclusion. The results show that STPE is higher for TBS than for BMD. Short-term PE for both BMD and TBS are adversely affected by increasing BMI but this effect is mitigated in the highest BMI category where use of the ‘thick’ scanning mode improves signal to noise ratio

Summary Statement. In a retrospective study, FE-based bone strength from CT data showed a greater ability than aBMD to discriminate proximal femur fractures versus controls. Introduction. Personalised Finite Element (FE) models from Computed Tomography (CT) data are superior to bone mineral density (BMD) in predicting proximal femoral strength in vitro [Cody, 1999]. However, results similar to BMD were obtained in vivo, in retrospective classification of generic prevalent fractures [Amin, 2011] and in prospective classification of femoral fractures [Orwoll, 2009]. The aim of this work is to test, in a case-control retrospective study, the ability of a different, validated FE modelling procedure [Schileo, 2008] to: (i) discriminate between groups of proximal femoral fractures and controls; (ii) individually classify fractures and controls. Patients & Methods. 55 women (22 incident low-trauma proximal femur fractures and 33 controls) were enrolled in 3 clinical centres in Emilia Romagna region, Italy. All received a full femoral CT and DXA exams (in acute conditions for fractured cases) with a standardised protocol. Femoral neck aBMD was measured from DXA. FE models were built from CT (right femur for controls, intact for fractured) [Schileo, 2008]. Differently from existing works, FE strength was calculated for a range of 12 physiological directions of hip joint reactions [Bergmann, 2001] and 10 fall directions [Grassi, 2012]. Bone strength (in stance and fall) was the minimum load inducing on the femoral neck surface an elastic principal strain value greater than the yield limit [Bayraktar, 2004]. Fracture classification was analysed through logistic regressions and AUC of ROC curves. Results. Mean FE strength and aBMD were significantly lower in the fractured than in the control group (33%, p<0.0001 for strength; 12% p=0.01 for aBMD). Logistic regression on single variables. All classifiers were significant (p<0.001, AUC=0.88 for both stance and fall FE strength, p=0.02, AUC=0.72 for aBMD). The statistical power of the logistic regressions [Vaeth, 2004] was >0.9 for FE strength, 0.86 for aBMD. Logistic regressions on multiple variables. Only FE strength was retained significant (p<0.001, AUC=0.88) when including aBMD in the regression. Adding age to the logistic regression, FE strength and age (but not aBMD) remained significant, with AUC=0.95. Discussion. FE strength could discriminate the fractured group better than aBMD and than [Keyak, 2011]. FE strength was a better fracture classifier than aBMD, and obtained AUC values slightly higher than [Amin, 2011; Orwoll, 2009]. The high statistical power mildens the small sample numerosity. Cases and controls were not age matched, but FE strength and age were found to be independent classifiers. In conclusion the proposed FE method was superior to aBMD in the classification of proximal femoral fractures

Recent studies have shown that bone mineral distribution is more heterogeneous in bone tissue from an animal model of osteoporosis and osteoporotic human vertebral trabeculae. These tissue alterations may play a role in bone fragility seen in osteoporosis, albeit that they are not detectable by current diagnostic techniques (dual-energy X-ray absorptiometry, DXA). Type II Diabetes Mellitus (T2DM) also increases a patient's fracture risk beyond what can be explained or diagnosed by DXA, and is associated with impaired bone cell function, compromised collagen structure and reduced mechanical properties. However, it is not currently known whether osteoporosis or T2DM leads to an increased mineral heterogeneity in the femoral head of humans, a common osteoporotic fracture site. In this study, we examine bone microarchitecture, mineralisation and mechanical properties of trabecular bone from osteoarthritic, diabetic and osteoporotic patients. We report that while osteoporotic trabecular bone has significantly deteriorated mechanical properties and microarchitecture compared to the other groups, there is also a significant increase in mean mineral content. Moreover, the heterogeneity of the mineral content in osteoporotic bone is significantly higher than osteoarthritic (+35%) and diabetic (+13%) groups. We propose that the compromised architecture following bone loss at the onset of osteoporosis alters the mechanical environment, which initiates compensatory changes in mineral content. We show for the first time that trabecular bone mineralisation is significantly more heterogeneous (+20%) in T2DM compared to osteoarthritic controls. Interestingly, bone microarchitecture and mechanical properties are not significantly different between diabetic and osteoarthritic groups despite this increase in mineral heterogeneity

Ageing is associated with a gradual and progressive bone loss, which predisposes to osteoporosis. Given the close relationship between the involutional bone loss and the underlying mechanism of osteoporosis, improving the understanding of the bone ageing process can lead to enhanced preventive and therapeutic strategies for osteoporosis. To facilitate this understanding, we develop a spatio-temporal atlas of ageing bone in the femur. We applied our method to a cohort of 11,576 Caucasian women (20–97 years). We amalgamated data from three different studies: 5095 women from the UK Biobank study, 1609 women from the OPUS study, and 5112 women from the MRC-Hip study. The scans are collected using either a Hologic QDR 4500A (Waltham, MA), a Lunar GE iDXA (Madison, WI), or a Lunar GE Prodigy (Madison, WI). Pixel BMD maps were exported using APEX v3.2 and Encore v16 for scans collected on Hologic Inc. and Lunar Corp., respectively. The method utilises a thin plate spline (TPS) registration to warp each scan to a reference mean shape. This image warping, termed Region Free Analysis (RFA), aims to eliminate morphological variation and establish a correspondence between pixel coordinates. At each pixel coordinate, the BMD evolution with ageing was modelled using smooth quantile curves. We deployed the R-package ‘VGAM’ to fit the smooth quantile curves. Cortical thinning was observed consistently with ageing around the shaft from the 60th onwards. A widespread bone loss was also observed in the trochanteric area. Quantile regression curves demonstrated different rates of bone loss at different anatomic locations. For example, bone loss was observed consistently in the mid-femoral neck, while bone mass was preserved the most in the inferior cortex. The developed atlas provides new insights into the spatial bone loss patterns, for which the conventional DXA analysis is insensitive

Osteocytes direct bone adaptation to mechanical loading (e.g., exercise), but the ways in which osteocytes detect loading remain unclear. We recently showed that osteocytes develop repairable plasma membrane disruptions (PMD) in response to treadmill-running exercise, and that these PMD initiate mechanotransduction. As treadmill running is a non-voluntary activity for rodents, our current goal was to determine whether osteocytes develop PMD with voluntary wheel running as a better model of physiological exercise. Male and female Hsd:ICR mice from lines selectively bred (>75 generations) to demonstrate high voluntary wheel running (“High Runners”) or non-selected control lines (“Control”) were studied (n=9 to 12 mice per sex per line, 4 lines each). At 12 weeks of age, half of the animals within each group were provided access to running wheels for 6 days while remaining mice had no wheel access. Tibias were collected at sacrifice and bone mineral density was analyzed by DXA. Osteocyte PMD were quantified by immunochemistry for intracellular albumin. Groups were compared with 3-factor ANOVA. Voluntary exercise (wheel access) significantly increased osteocyte PMD (+16.4%, p=0.013). PMD-labelled osteocytes did not differ between sexes (p=0.415). Male mice had significantly greater BMD (p=0.0007) and BMC (<0.0001) than females. Interestingly, mice with wheel access had significantly lower BMD and BMC compared to mice without wheel access (p<0.004), and high runner lines had significantly lower BMD (p=0.001) and BMC (p<0.0001) than control lines. This may reflect new bone formation in the exercising mice, as newly formed bone is less mineralized than older bone. Data from this experiment support the idea that loading-induced disruptions develop in the osteocyte plasma membrane during both voluntary (wheel running) and forced (treadmill, shown previously) physical activity. These studies support the role of plasma membrane disruptions as a mechanosensation mechanism in osteocytes

Introduction. DXA areal-bone-mineral-density (aBMD) is used clinically as a surrogate for true volumetric-BMD to assess bone fragility. Trabecular-Bone-Score (TBS) provides an assessment of bone quality based on the DXA-derived two-dimensional images. Calculated from bone area (BA), aBMD may under- or overestimate true BMD in individuals with relatively low and high BA respectively. This study investigated relationships between BA at the lumbar-spine (L1–L4) and measurements of BMD and TBS. Method. Lumbar spine scans were performed (GE Lunar Prodigy) on 114 women (mean 53 yrs). The study population was divided by L1–L4 BA using the 20th and 80th centiles, and BMD v TBS correlations calculated for the subgroups. BMD and TBS, converted to Z-scores, were correlated with BA. Results. For the whole group, r = 0.23 for BMD v BA, whereas r = −0.12 for TBS v. BA: the correlation between BMD and TBS was r=0.38. Correlations between BMD and TBS for BA subgroups were r = 0.23, r=0.44 and r=0.59 for the >20th, 20th −80th and >80th centile groups respectively. Conclusion. Low correlation between BMD and TBS for the entire group indicates that TBS reflects some bone quality properties unrelated to BMD. The correlation of BMD with BA suggests that it incorrectly estimates true BMD at BA extremes. Correlation for BMD v TBS in the lowest area-subgroup was substantially lower than for the middle and highest area subgroups suggesting that TBS may afford valuable complementary information on bone fragility at the lowest extreme of BA where distortions in BMD measurement potentially occur

Summary Statement. It is now possible to diagnose osteoporosis using incidental CT scans; this approach has been used to objectively demonstrate the role of osteoporosis in fracture in ankylosing spondylitis patients. Background. In advanced disease, Ankylosing Spondylitis (AS) is frequently associated with a reduction in bone mineral density (BMD), this contributes to pain and predisposes to fractures. Quantifying this reduction in BMD is complicated by the simultaneous processes occurring, in which there is both an overgrowth of bone (syndesmophytes) and a concurrent loss of trabecular bone. Traditional methods such as dual-energy X-ray absorptiometry (DXA) struggle to generate accurate estimates for BMD in these patients. It has recently become possible to diagnose osteoporosis, with a high sensitivity and specificity, using incidental CT scans of the L1 vertebra. The purpose of this study was to evaluate the use of opportunistic CT screening in the diagnosis of osteoporosis in patients with AS who had sustained vertebral fractures. Patients & Methods. Following Institutional review board approval, patients with AS who presented, with acute fractures of the spine, to our facility between 2004 and 2013 were reviewed to assess whether or not they had a Computed Tomography (CT) scan of the abdomen on admission or in the 6 months before or after injury. In addition, patients were also required to have signs of advanced AS such as the presence of syndesmophytes and syndesmophyte bridging; patients with fractures through L1 were excluded. Of those fitting the criteria, a region of Interest (ROI) was generated over the body of L1, Hounsfield unit (HU) were then measured. Results. Of the 42 patients reviewed, a total of 17 AS patients fit the above criteria. 15 were male and 2 were female, mean age of the whole cohort was 69.9years (range 22–85; SD 15.9). Using a threshold balanced for sensitivity and specificity (<135 HU) which differentiates between osteopenia and osteporosis, 14 (82%) patients were found to have a BMD less than 135HU; a higher threshold (<160 HU) with 90 % sensitivity for differentiating osteoporosis from osteopenia was applied to the group, and 15 patients (88%) were found to be osteoporotic. Of note all the females in the study were osteoporotic. Discussion and Conclusion. This study demonstrates, for the first time, using opportunistic CT screening, that a high proportion of AS patients who sustain fractures have osteoporosis; this overcomes the difficulties that have been encountered with the use of DXA in this unique group of patients. This simple and accessible method saves on excess cost and exposure to radiation. With a high sensitivity, patients identified using this method can then be managed more proactively. We believe these data have the potential to significantly impact the day to day management of patients with spondyloarthropathies

Summary Statement. Using abdominal CT scans to evaluate bone mineral density following acute fractures of the thoracic and lumbar spine demonstrates significant levels of osteoporosis in older patients; this approach may help save on time and resources, and reduce unnecessary radiation exposure. Introduction. While a reduction in bone mineral density (BMD) is associated with aging, relatively few patients have formal dual-energy X-ray absorptiometry (DXA) to quantify the magnitude of bone loss, as they age. This loss of bone may predispose to fractures. Recent data, which correlates mean Hounsfield units (HU) in an area of the L1 vertebra with BMD, now makes it possible to screen for osteoporosis using incidental abdominal Computed Tomography (CT) scans to measure bone density. This innovation has the potential to reduce both cost and radiation exposure, and also make it easier to identify patients who may be at risk. The aims of this study were to evaluate the utility of this approach in patients with acute thoracic and lumbar spine fractures and to evaluate the impact of aging on BMD, using CT screening. Patients & Methods. Following institutional review board approval, we performed a retrospective study of patients who presented to a level I trauma center with acute fractures of the thoracic and lumbar spine between 2010 and 2013; patients also had to have had an abdominal (or L1) CT scan either during the admission or in the 6 months before or after their injury. Using a picture archiving and communication (PACS) system, we generated regions of interest (ROI) of similar size in the body of L1 (excluding the cortex) and computed mean values for HU. Values derived were compared against threshold values which differentiate between osteoporosis and osteopenia - for specificity of 90%, a threshold of 110 was set; for balanced sensitivity and specificity, a threshold of <135 HU was set and for 90% sensitivity a threshold of <160 HU was set. A student's t test was used to compare the age stratified mean HU (younger than 65yrs; 65yrs and older), while Fisher's exact test was used to perform aged stratified comparisons between the proportions of patients above and below the thresholds outlined (in each of the three threshold groups). Results. A total of 124 patients were evaluated, with 74 having thoracic and 50 having lumbar fractures. Among those with thoracic fractures, there were 33patients in the younger cohort, who also had a mean BMD of 196.51HU and 41 in the older cohort, who had mean BMD of 105.90HU (p<0.001). In patients with lumbar fractures, 27 patients were in the younger cohort, with mean BMD of 192.26HU and 23 patients in the older cohort with mean BMD of 114.31HU (p<0.001). At the threshold of 110 HU, set for specificity, the magnitude of difference between the age stratified cohorts was greater in the thoracic spine (p<0.001 vs. p=0.003). At the other thresholds: 135HU (balanced for sensitivity and specificity) and 160 HU (90% sensitivity), age of 65 years or older was significantly associated with reduction in CT derived measure of BMD (p<0.001 in all cases). Discussion. This study demonstrates the relative frequency of osteoporosis in acute fractures of the thoracic and lumbar spine, and how this changes with age; it is also the first study to do this using opportunistic CT scans. There seems to be a strong association between a reduction in bone mineral density and advanced age, in patients presenting with acute fractures of the spine. This approach may save on the extra cost and additional radiation exposure that may be associated with DXA scanning; in addition, it may help provide clinicians and patients with an approach to monitor developing problems with BMD before it becomes clinically apparent, especially in younger patients

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Hydroxyapatite-coated standard anatomical and customised femoral stems are designed to transmit load to the metaphyseal part of the proximal femur in order to avoid stress shielding and to reduce resorption of bone. In a randomised in vitro study, we compared the changes in the pattern of cortical strain after the insertion of hydroxyapatite-coated standard anatomical and customised stems in 12 pairs of human cadaver femora. A hip simulator reproduced the physiological loads on the proximal femur in single-leg stance and stair-climbing. The cortical strains were measured before and after the insertion of the stems.

Significantly higher strain shielding was seen in Gruen zones 7, 6, 5, 3 and 2 after the insertion of the anatomical stem compared with the customised stem. For the anatomical stem, the hoop strains on the femur also indicated that the load was transferred to the cortical bone at the lower metaphyseal or upper diaphyseal part of the proximal femur.

The customised stem induced a strain pattern more similar to that of the intact femur than the standard, anatomical stem.

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.