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Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from dual‐energy X‐ray absorptiometry scans in 1327 individuals (688 female) at 60 to 64 years in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two‐line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position, and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient, 0.023; 95% CI, 0.000‐0.047; P = .05) and direct angle measurement. Modest associations between walking age and less variation in anterior‐posterior vertebral size caudally (SSM6) were also observed (0.021; 95% CI, −0.002 to 0.044; P = .07). Sex interactions showed that later walking was associated with larger relative vertebral anterior‐posterior dimensions in men (SSM3; −0.043; 95% CI, −0.075 to 0.01; P = .01) but not women (0.018; 95% CI, −0.0007 to 0.043; P = .17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on the features of spine morphology with clinical significance.

Background Ageing is associated with sarcopenia, osteoporosis, and increased fall risk, all of which contribute to increased fracture risk. Mechanically, bone strength adapts in response to forces created by muscle contractions. Adaptations can be through changes in bone size, geometry, and bending strength. Muscle mass is often used as a surrogate for muscle force; however, force can be increased without changes in muscle mass. Increased fall risk with ageing has been associated with a decline in muscle power—which is a measure of mobility. The aims of this study were as follows: (i) to investigate the relationship between muscle parameters in the upper and lower limbs with age in UK men and the influence of ethnicity on these relationships; (ii) to examine the relationships between jump force/grip strength/cross-sectional muscle area (CSMA) with bone outcomes at the radius and tibia. Methods White European, Black Afro-Caribbean, and South Asian men aged 40–79 years were recruited from Manchester, UK. Cortical bone mineral content, cross-sectional area, cortical area, cross-sectional moment of inertia, and CSMA were measured at the diaphysis of the radius and tibia using peripheral quantitative computed tomography. Lower limb jump force and power were measured from a single two-legged jump performed on a ground-reaction force platform. Grip strength was measured using a dynamometer. Associations between muscle and bone outcomes was determined using linear regression with adjustments for age, height, weight, and ethnicity. Results Three hundred and one men were recruited. Jump force was negatively associated with age; for every 10 year increase in age, there was a 4% reduction in jump force (P

Background: Breast cancer diagnosis may be a teachable moment for lifestyle behaviour change and to prevent adjuvant therapy associated weight gain. We assessed the acceptability and effectiveness of two weight control programmes initiated soon after breast cancer diagnosis to reduce weight amongst overweight or obese women and prevent gains in normal-weight women.Methods: Overweight or obese (n = 243) and normal weight (n = 166) women were randomised to a three-month unsupervised home (home), a supervised community weight control programme (community) or to standard written advice (control). Primary end points were change in weight and body fat at 12 months. Secondary end points included change in insulin, cardiovascular risk markers, quality of life and cost-effectiveness of the programmes.Results: Forty-three percent of eligible women were recruited. Both programmes reduced weight and body fat: home vs. control mean (95% CI); weight −2.3 (−3.5, −1.0) kg, body fat −1.6 (−2.6, −0.7) kg, community vs. control; weight −2.4 (−3.6, −1.1) kg, body fat −1.4 (−2.4, −0.5) kg (all p Conclusions: The programmes were equally effective for weight control, but the community programme had additional benefits.

The increasing use of dual-energy X-ray absorptiometry (DXA) in children has led to the need for robust reference data for interpretation of scans in daily clinical practice. Such data need to be representative of the population being studied and be "future-proofed" to software and hardware upgrades. The aim was to combine all available pediatric DXA reference data from seven UK centers to create reference curves adjusted for age, sex, ethnicity, and body size to enable clinical application, using in vivo cross-calibration and making data back and forward compatible. Seven UK sites collected data on GE Lunar or Hologic Scanners between 1996 and 2012. Males and females aged 4 to 20 years were recruited (n = 3598). The split by ethnic group was white 2887; South Asian 385; black Afro-Caribbean 286; and mixed heritage 40. Scans of the total body and lumbar spine (L1 to L4 ) were obtained. The European Spine Phantom was used to cross-calibrate the 7 centers and 11 scanners. Reference curves were produced for L1 to L4 bone mineral apparent density (BMAD) and total body less head (TBLH) and L1 to L4 areal bone mineral density (aBMD) for GE Lunar Prodigy and iDXA (sex- and ethnic-specific) and for Hologic (sex-specific). Regression equations for TBLH BMC were produced using stepwise linear regression. Scans of 100 children were randomly selected to test backward and forward compatibility of software versions, up to version 15.0 for GE Lunar and Apex 4.1 for Hologic. For the first time, sex- and ethnic-specific reference curves for lumbar spine BMAD, aBMD, and TBLH aBMD are provided for both GE Lunar and Hologic scanners. These curves will facilitate interpretation of DXA data in children using methods recommended in ISCD guidelines. The databases have been created to allow future updates and analysis when more definitive evidence for the best method of fracture prediction in children is agreed. © 2016 American Society for Bone and Mineral Research.

Context: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross-sectional, or lacking gold standard bone technologies or information on hormone replacement therapy (HRT) or surgical treatment. Objective: The objective of the study was to investigate age at menopause, length of reproductive life, and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size, and strength in women aged 60–64 years. Design: This was a birth cohort study that followed up for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories. Setting: The study was conducted in England, Scotland, and Wales. Participants: Participants included 848 women with a known type of menopause and bone measures at 60–64 years. Main Outcome Measures: Peripheral quantitative computed tomography measurements of the distal radius total and trabecular vBMD were measured. Diaphyseal radius total and medullary cross-sectional area, cortical vBMD, and polar strength strain index (SSI); dual-energy x-ray absorptiometry measurements of aBMD at the lumbar spine and total hip were also measured. Results: A 10-year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% confidence interval [CI] 1.3%–15.1%, P = .02) greater trabecular vBMD and a 6.0% (95% CI 0.51%–11.5%, P = .03) greater total vBMD; findings were similar for length of reproductive life. A 10-year difference in HRT use was associated with a 6.0% (95% CI 2.6%–9.3%, P < .001) greater polar SSI and a 0.9% (95% CI 0.4%–1.5%, P = .001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for peripheral quantitative computed tomography. Conclusions: The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater radius cortical vBMD and polar SSI and aBMD., Later natural menopause and longer reproductive life, assessed prospectively, were associated with trabecular vBMD in early old age; HRT was associated with cortical vBMD, strength and spine aBMD.

Oral glucocorticoids (GC) preserve muscle strength and prolong walking in boys with Duchenne muscular dystrophy (DMD). Although vertebral fractures have been reported in boys taking GC, fracture rates for different GC regimes have not been investigated. The aim of this pragmatic longitudinal study was to compare growth, body mass, bone mineral density (BMD), vertebral fractures (VF) and ambulatory status in boys with DMD on daily (DAILY) or intermittent (INTERMITTENT), oral GC regimens. A convenience sample of 50 DMD boys from two centres was included in the study; 25 boys each were on the DAILY or INTERMITTENT regimen. Size adjusted lumbar spine BMD (LS BMAD), total body less head BMD (TBLH), by DXA and distal forearm bone densities by pQCT, GC exposure, VF assessment and ambulatory status were analysed at three time points; baseline, 1 and 2 years. At baseline, there were no differences in age, GC duration or any bone parameters. However, DAILY boys were shorter (height SDS DAILY = -1.4(0.9); INTERMITTENT = -0.8(1.0), p = 0.04) with higher BMI (BMI SDS DAILY = 1.5(0.9); INTERMITTENT = 0.8(1.0), p = 0.01). Over 2 years, DAILY boys got progressively shorter (delta height SDS DAILY = -0.9(1.1); INTERMITTENT = +0.1(0.6), p

Background: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the luteinizing hormone releasing hormone (LHRH) analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention. Methods: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone (C-Control) or screening in addition to monthly subcutaneous injections of 3.6 mg goserelin and continuous 60 mg raloxifene daily orally (T-Treated) for 2 years. The primary endpoint was therapy adherence. Secondary endpoints were toxicity/quality of life, change in bone density, and mammographic density. Results: A total of 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20 of 38 (52%) of women completed the 2-year period of study compared with the C-arm (27/37, 73.0%). Dropouts were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety, and less cancer worry. Lumbar spine bone density declined by 7.0% and visually assessed mammographic density by 4.7% over the 2-year treatment period. Conclusions: Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher dropout rates. Raloxifene may preserve bone density, but reduction in mammographic density reversed after treatment was completed. Impact: This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option. Cancer Epidemiol Biomarkers Prev; 27(1); 58–66. ©2017 AACR.

Osteoporotic vertebral fractures (VFs) are under-diagnosed, creating an opportunity for computer-aided, opportunistic fracture identification in clinical images. VF diagnosis and grading in clinical practice involves comparisons of vertebral body heights. However, machine vision systems can provide a high-resolution segmentation of the vertebrae and fully characterise their shape and appearance, potentially allowing improved diagnostic accuracy. We compare approaches based on vertebral heights to shape/appearance modelling combined with k-nearest neighbours and random forest (RF) classifiers, on both dual-energy X-ray absorptiometry images and computed tomography image volumes. We demonstrate that the combination of RF classifiers and appearance modelling, which is novel in this application, results in a significant (up to 60% reduction in false positive rate at 80% sensitivity) improvement in diagnostic accuracy.

Objective Randomized trials in men with testosterone deficiency have provided evidence of short-term effects of testosterone therapy on muscle and fat mass but it is unclear whether this persists over a longer period or how testosterone affects women. We examined whether the midlife decline in testosterone relates to fat and lean mass in both sexes. Methods Data were collected from 440 men and 560 women participating in the 1946 British birth cohort study with testosterone measured at 53 and/or 60-64 years. Fat and appendicular lean mass were measured at 60-64 years using dual-energy X-ray absorptiometry. Results Mean free testosterone concentrations were lower at 60-64 than 53 years, by 26% in both sexes. At both ages testosterone was negatively associated with fat mass in men and positively associated in women. A larger decline in free testosterone was associated with higher fat mass in men but with lower fat mass among women. In contrast, declines in testosterone were not associated with lean mass in either sex. Conclusions Our findings suggest sex-divergent relationships between testosterone and fat mass and their distribution but do not support the hypothesis that midlife declines in testosterone lead to lower lean mass.

Background In men, the long-term consequences of low serum levels of sex steroids, vitamin D metabolites, and insulin-like growth factor 1 (IGF-1) on the evolution of muscle mass, muscle strength, or physical performance are unclear. Moreover, there are no data about the relationship between these hormones and incident sarcopenia defined as low muscle mass and function. The aim of this study was to determine whether the baseline levels of sex hormones, vitamin D metabolites, and IGF-1 predict changes in muscle mass, muscle strength, physical performance, and incident sarcopenia. Methods In 518 men aged 40–79 years, recruited for participation in the European Male Ageing Study, total, free, and bioavailable testosterone (T), oestradiol (E), sex hormone-binding globulin, IGF-1, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone were assessed at baseline. Appendicular lean mass (aLM), gait speed, and grip strength were measured at baseline and after a mean follow-up of 4.3 years. Sarcopenia was defined by the definition of Baumgartner (relative aLM ≤7.26 kg/m2), the International Working Group on Sarcopenia (IWGS), and the European Working Group on Sarcopenia in Older People (EWGSOP). Results aLM significantly decreased from age 50 years, while gait speed and grip strength significantly decreased from age 70 years. The incidence of sarcopenia by the definitions of Baumgartner, IWGS, and EWGSOP was 8.1%, 3.0%, and 1.6%, respectively. After adjustment for age, centre, body mass index, smoking, and number of comorbidities at baseline, baseline levels of T and vitamin D metabolites were not associated with change in aLM, gait speed, and/or grip strength, while a high baseline level of total E2 was associated with a greater decrease in aLM. In men aged ≥70 years, low IGF-1 was associated with a greater decrease in gait speed. Baseline endocrine variables were not independently associated with an increased risk of incident sarcopenia by any definition. Conclusions Low levels of T and 25OHD do not predict loss of muscle mass, gait speed, or grip strength in middle-aged and elderly community-dwelling European men. Low IGF-1 predicts change in gait speed in men aged ≥70 years.

This work addresses the problem of automatic estimation of bone age in children and young adults. Bone age assessment is important for diagnosing and monitoring growth and endocrine disorders. We have constructed a system which uses Statistical Models of Shape and Appearance to locate bones in a radiograph and to predict bone age. By analyzing the performance on a data-set of about 600 digitized radiograph of normal children we show how Random Forest Regression voting in a Contrained Local models framework (RFRV — CLM) are sufficient to initialize an automatic registration algorithm. We built global models of whole hand and local models of individual bones. We used the same RFRV — CLM models to locate salient bones of the hand. We improved our age estimation results by using multiple local age group models and multiple local age predictors. We obtained an accuracy of mean point-to-point errors of 0.87mm on sparse points placement for initialization of automatic registrations. Our Bone age assessment methodology achieved an accuracy of mean absolute error of 0.41±0.02 years and 0.47 ± 0.03 years for female and male respectively.

Excess weight at breast cancer diagnosis and weight gain during treatment are linked to increased breast cancer specific and all-cause mortality. The Breast—Activity and Healthy Eating After Diagnosis (B-AHEAD) trial tested 2 weight loss diet and exercise programmes versus a control receiving standard written advice during adjuvant treatment. This article identifies differences in characteristics between patients recruited from the main trial site to those of the whole population from that site during the recruitment period and identifies barriers to recruitment. A total of 409 patients with operable breast cancer were recruited within 12 weeks of surgery. We compared demographic and treatment factors between women recruited from the main trial coordinating site (n = 300) to the whole breast cancer population in the center (n = 532). Uptake at the coordinating site was 42%, comparable to treatment trials in the unit (47%). Women recruited were younger (55.9 vs 61.2 years, P < .001), more likely to live in least deprived postcode areas (41.7% vs 31.6%, P = .004), and more likely to have screen-detected cancers (55.3% vs 48.7%, P = .026) than the whole breast cancer population. The good uptake highlights the interest in lifestyle change around the time of diagnosis, a challenging time in the patient pathway, and shows that recruitment at this time is feasible. Barriers to uptake among older women and women with a lower socioeconomic status should be understood and overcome in order to improve recruitment to future lifestyle intervention programs.

Objectives To investigate the effect of pubertal timing, assessed in adolescence, on bone size, strength and density in men and women in early old age. Design A British birth cohort study with prospective indicators of pubertal timing based on age at menarche, clinical assessment of pubertal stage, and growth tempo from serial height measures, and bone measures derived from peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) at 60-64 years of age among 866 women and 792 men. Methods A first set of regression models investigated the relationships between pubertal timing and bone size, strength and density, adjusting for current height and weight, smoking and adult socioeconomic position. To make an equivalent comparison between men and women, the percentage difference in bone outcomes was calculated for a 5-year difference in age at menarche, and in men a comparison between those who were fully mature or pre-adolescent at 14.5 years. A second set of models investigated the percentage difference in bone outcomes for a 5-year difference in timing of peak height velocity (height tempo) derived from longitudinal growth modelling (Superimposition by Translation and Rotation model; SITAR). Results After adjustment for current height and weight, a 5-year increase in age at menarche was associated with an 8% [95% confidence interval (CI) -17%, 0.5%,P¼0.07) lower trabecular volumetric bone mineral density (vBMD); men who were pre-adolescent at 14.5 years had a 9%, (95% CI -14%, -4%;P¼0.001) lower trabecular vBMD compared with those who had been fully mature. Other confounders did not attenuate these estimates further. Patterns of association were similar but somewhat weaker for lumbar spine and total hip areal BMD. Age at peak height velocity was associated with even larger differences in BMD in men and women, and was negatively associated with bone size and strength. Conclusions The association between later puberty and lower BMD persists into early old age. The 9-10% lower trabecular vBMD in later compared with earlier maturers could be clinically important given a rate of bone loss from midlife of 1-2% a year and the negative association between BMD and fracture.

The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition statistics to describe and quantify such shapes from images; it uses principal components analysis to generate modes of variation describing each image in terms of a set of numerical scores after removing global size variation. We used SSM to quantify the shapes of the hip and the lumbar spine in dual‐energy x‐ray absorptiometry (DXA) images from 1511 individuals in the MRC National Survey of Health and Development at ages 60–64 years. We compared shapes of both joints in men and women and hypothesised that hip and spine shape would be strongly correlated. We also investigated associations with height, weight, body mass index (BMI) and local (hip or lumber spine) bone mineral density. In the hip, all except one of the first 10 modes differed between men and women. Men had a wider femoral neck, smaller neck‐shaft angle, increased presence of osteophytes and a loss of the femoral head/neck curvature compared with women. Women presented with a flattening of the femoral head and greater acetabular coverage of the femoral head. Greater weight was associated with a shorter, wider femoral neck and larger greater and lesser trochanters. Taller height was accompanied by a flattening of the curve between superior head and neck and a larger lesser trochanter. Four of the first eight modes describing lumbar spine shape differed between men and women. Women tended to have a more lordotic spine than men with relatively smaller but caudally increasing anterior‐posterior (a‐p) vertebral diameters. Men were more likely to have a straighter spine with larger vertebral a‐p diameters relative to vertebral height than women, increasing cranially. A weak correlation was found between body weight and a‐p vertebral diameter. No correlations were found between shape modes and height in men, whereas in women there was a weak positive correlation between height and evenness of spinal curvature. Linear relationships between hip and spine shapes were weak and inconsistent in both sexes, thereby offering little support for our hypothesis. In conclusion, men and women entering their seventh decade have small but statistically significant differences in the shapes of their hips and their spines. Associations with height, weight, BMI and BMD are small and correspond to subtle variations whose anatomical significance is not yet clear. Correlations between hip and spine shapes are small.

Later age at onset of independent walking is associated with lower leg bone strength in childhood and adolescence. However, it is unknown whether these associations persist into older age or whether they are evident at axial (central) or upper limb sites. Therefore, we examined walking age obtained at age 2 years and bone outcomes obtained by dual‐energy X‐ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at ages 60 to 64 years in a nationally representative cohort study of British people, the MRC National Survey of Health and Development. It was hypothesized that later walking age would be associated with lower bone strength at all sites. Later independent walking age was associated with lower height‐adjusted hip (standardized regression coefficients with 95% confidence interval [CI] –0.179 [–0.251 to –0.107]), spine (–0.157 [–0.232 to –0.082]), and distal radius (–0.159 [–0.245 to –0.073]) bone mineral content (BMC, indicating bone compressive strength) in men (all p

Maximizing peak bone mass in childhood is relevant to optimizing bone health in later life, so the study of the skeleton in children in health and disease is important. Dual-energy X-ray absorptiometry (DXA) is the most widely used clinical tool for the assessment of bone status in children. Technological developments in DXA enable vertebral fracture assessment at much lower ionizing radiation doses than spinal radiographs. Quantitative computed tomography remains predominantly a research tool but has some advantages over DXA in not being size dependent. High-resolution peripheral computed tomography measures trabecular and cortical bone microstructure but is technically challenging, particularly in children, and not widely available, so it is unlikely to be used in clinical practice. Other quantitative techniques (quantitative magnetic resonance imaging, digital X-ray absorptiometry, quantitative ultrasound) have been applied in children but remain research applications, and they are only covered briefly in this review.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Background Ageing is associated with sarcopenia, osteoporosis, and increased fall risk, all of which contribute to increased fracture risk. Mechanically, bone strength adapts in response to forces created by muscle contractions. Adaptations can be through changes in bone size, geometry, and bending strength. Muscle mass is often used as a surrogate for muscle force; however, force can be increased without changes in muscle mass. Increased fall risk with ageing has been associated with a decline in muscle power—which is a measure of mobility. The aims of this study were as follows: (i) to investigate the relationship between muscle parameters in the upper and lower limbs with age in UK men and the influence of ethnicity on these relationships; (ii) to examine the relationships between jump force/grip strength/cross‐sectional muscle area (CSMA) with bone outcomes at the radius and tibia. Methods White European, Black Afro‐Caribbean, and South Asian men aged 40–79 years were recruited from Manchester, UK. Cortical bone mineral content, cross‐sectional area, cortical area, cross‐sectional moment of inertia, and CSMA were measured at the diaphysis of the radius and tibia using peripheral quantitative computed tomography. Lower limb jump force and power were measured from a single two‐legged jump performed on a ground‐reaction force platform. Grip strength was measured using a dynamometer. Associations between muscle and bone outcomes was determined using linear regression with adjustments for age, height, weight, and ethnicity. Results Three hundred and one men were recruited. Jump force was negatively associated with age; for every 10 year increase in age, there was a 4% reduction in jump force (P

Background: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2–26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5–20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) bone health outcomes at 60–64 years.Methods: NSHD data were analysed using Super-Imposition by Translation And Rotation (SITAR) growth curve analysis, either alone or jointly with ALSPAC data. Improved estimation of pubertal growth parameters of size, tempo and velocity was assessed by changes in model fit and correlations with contemporary measures of pubertal timing. Bone outcomes of radius [trabecular volumetric bone mineral density (vBMD) and diaphysis cross-sectional area (CSA)] were regressed on the SITAR parameters, adjusted for current body size.Results: The NSHD SITAR parameters were better estimated in conjunction with ALSPAC, i.e. more strongly correlated with pubertal timing. Trabecular vBMD was associated with early height tempo, whereas diaphysis CSA was related to weight size, early tempo and slow velocity, the bone outcomes being around 15% higher for the better vs worse growth pattern.Conclusions: By pooling NSHD and ALSPAC data, SITAR more accurately summarized pubertal growth and weight gain in NSHD, and in turn demonstrated notable associations between pubertal timing and later bone outcomes. These associations give insight into the importance of the pubertal period for future skeletal health and osteoporosis risk.

A semi-anthropomorphic 'distal radius like' phantom, developed by Kalender and Ruegsegger for use in peripheral bone densitometry using single photon (DPA) dual X-ray (DXA) and quantitative computed tomography (QCT) machines, has been studied with a view to cross-calibrating different types and brands of densitometers in current use. In the context of an EU 'Concerted Action' (second Framework Programme) the phantom was repeatedly measured on six SPA machines, three DXA machines and nine QCT machines (545 measurements). Linear regression equations were derived, individual to each machine, which allowed the derivation of 'standardized densities'. In this way we converted measurements made by machines of the same modality to a common scale of measurements. Two machines (one DXA, one SPA) showed statistically significant instability over time emphasising the need for rigorous quality control in the application of densitometry. In other respects these results provide an encouraging basis for the derivation of standardized normative ranges and the more effective use of peripheral densitometry in future clinical and epidemiological studies.

Context: Vitamin D is essential for bone health in adolescence, when there is rapid bone mineral content accrual. Because cutaneous sun exposure provides Vitamin D, there is no recommended oral intake for UK adolescents. Objective: Our objective was to assess seasonal Vitamin D status and its contributors in white Caucasian adolescents and examine bone health in those found deficient. Design: Prospective cohort study was undertaken. Setting: Six schools in Greater Manchester, UK, were included. Participants: Participants were 131 adolescents between 12 and 15 years of age. Intervention(s): Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sun exposure, and dietary Vitamin D. Adolescents deficient (25OHD

We describe a system for fully automatic vertebra localisation and segmentation in 3D CT volumes containing arbitrary regions of the spine, with the aim of detecting osteoporotic fractures. To avoid the difficulties of high-resolution manual annotation on overlapping structures in 3D, the system consists of several 2D operations. First, a Random Forest regressor is used to localise the spinal midplane in a coronal maximum intensity projection. A 2D sagittal image showing the midplane is then produced. A second set of regressors are used to localise each vertebral body in this image. Finally, a Random Forest Regression Voting Constrained Local Model is used to segment each detected vertebra.

This chapter provides an overview of the current densitometry techniques that are used in children. The strengths and limitations of each of the techniques are discussed. Dualenergy x-ray absorptiometry (DXA) is discussed only briefly, as the remainder of this book concentrates on this technique in detail. Table 1 provides a technical overview of costs, uses, precision, and radiation exposure associated with densitometry methods. Radiation doses associated with other imaging modalities and with natural background sources are provided for comparison in Table 2.

Relatively little is known about the bone health of ethnic groups within the UK and data are largely restricted to women. The aim of this study was to investigate ethnic differences in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), bone geometry and strength in UK men. White European, Black Afro-Caribbean and South Asian men aged over 40 years were recruited from Greater Manchester, UK. aBMD at the spine, hip, femoral neck and whole body were measured by DXA. Bone geometry, strength and vBMD were measured at the radius and tibia using pQCT at the metaphysis (4%) and diaphysis (50% radius; 38% tibia) sites. Adjustments were made for age, weight and height. Black men had higher aBMD at the whole body, total hip and femoral neck compared to White and South Asian men independent of body size adjustments, with no differences between the latter two groups. White men had longer hip axis lengths than both Black and South Asian men. There were fewer differences in vBMD but White men had significantly lower cortical vBMD at the tibial diaphysis than Black and South Asian men (p, Highlights • Ethnic differences in bone health were investigated in UK men using DXA and pQCT • Areal BMD was highest in Black Afro-Caribbean compared to White and South Asian men • Black Afro-Caribbean men had the most advantageous geometry and bone distribution • No differences in areal BMD between South Asian and White men • At the tibia, South Asians had thinner cortices and lower strength than White men

Purpose To evaluate the performance of three imaging methods (radiography, dual-energy x-ray absorptiometry [DXA], and quantitative computed tomography [CT]) and that of a numerical analysis with finite element modeling (FEM) in the prediction of failure load of the proximal femur and to identify the best densitometric or geometric predictors of hip failure load. Materials and Methods Institutional review board approval was obtained. A total of 40 pairs of excised cadaver femurs (mean patient age at time of death, 82 years ± 12 [standard deviation]) were examined with (a) radiography to measure geometric parameters (lengths, angles, and cortical thicknesses), (b) DXA (reference standard) to determine areal bone mineral densities (BMDs), and (c) quantitative CT with dedicated three-dimensional analysis software to determine volumetric BMDs and geometric parameters (neck axis length, cortical thicknesses, volumes, and moments of inertia), and (d) quantitative CT-based FEM to calculate a numerical value of failure load. The 80 femurs were fractured via mechanical testing, with random assignment of one femur from each pair to the single-limb stance configuration (hereafter, stance configuration) and assignment of the paired femur to the sideways fall configuration (hereafter, side configuration). Descriptive statistics, univariate correlations, and stepwise regression models were obtained for each imaging method and for FEM to enable us to predict failure load in both configurations. Results Statistics reported are for stance and side configurations, respectively. For radiography, the strongest correlation with mechanical failure load was obtained by using a geometric parameter combined with a cortical thickness (r(2) = 0.66, P < .001; r(2) = 0.65, P < .001). For DXA, the strongest correlation with mechanical failure load was obtained by using total BMD (r(2) = 0.73, P < .001) and trochanteric BMD (r(2) = 0.80, P < .001). For quantitative CT, in both configurations, the best model combined volumetric BMD and a moment of inertia (r(2) = 0.78, P < .001; r(2) = 0.85, P < .001). FEM explained 87% (P < .001) and 83% (P < .001) of bone strength, respectively. By combining (a) radiography and DXA and (b) quantitative CT and DXA, correlations with mechanical failure load increased to 0.82 (P < .001) and 0.84 (P < .001), respectively, for radiography and DXA and to 0.80 (P < .001) and 0.86 (P < .001) , respectively, for quantitative CT and DXA. Conclusion Quantitative CT-based FEM was the best method with which to predict the experimental failure load; however, combining quantitative CT and DXA yielded a performance as good as that attained with FEM. The quantitative CT DXA combination may be easier to use in fracture prediction, provided standardized software is developed. These findings also highlight the major influence on femoral failure load, particularly in the trochanteric region, of a densitometric parameter combined with a geometric parameter. (©) RSNA, 2016 Online supplemental material is available for this article.

We describe a method for automatic detection and localisation of vertebrae in clinical images that was designed to avoid making a priori assumptions of how many vertebrae are visible. Multiple random forest regressors were trained to identify vertebral end-plates, providing estimates of both the location and pose of the vertebrae. The highest-weighted responses from each model were combined using a Hough-style voting array. A graphical approach was then used to extract contiguous sets of detections representing neighbouring vertebrae, by finding a path linking modes of high weight, subject to pose constraints. The method was evaluated on 320 lateral dual-energy X-ray absorptiometry spinal images with a high prevalence of osteoporotic vertebral fractures, and detected 92 % of the vertebrae between T7 and L4 with a mean localisation error of 2.36 mm. When used to initialise a constrained local model segmentation of the vertebrae, the method increased the incidence of fit failures from 1.5 to 2.1 % compared to manual initialisation, and produced no difference in fracture classification using a simple classifier.

Evidence for the contribution of individual foods and nutrients to bone health is weak. Few studies have considered hypothesis‐based dietary patterns and bone health. We investigated whether a protein‐calcium‐potassium–rich (PrCaK‐rich) dietary pattern over the adult life course, was positively associated with bone outcomes at 60 to 64 years of age. Diet diaries were collected at ages 36, 46, 53, and 60 to 64 years in 1263 participants (661 women) from the MRC National Survey of Health and Development. DXA and pQCT measurements were obtained at age 60 to 64 years, including size‐adjusted bone mineral content (SA‐BMC) and volumetric bone mineral density (vBMD). A food‐based dietary pattern best explaining dietary calcium, potassium, and protein intakes (g/1000 kcal) was identified using reduced rank regression. Dietary pattern Z‐scores were calculated for each individual, at each time point. Individual trajectories in dietary pattern Z‐scores were modeled to summarize changes in Z‐scores over the study period. Regression models examined associations between these trajectories and bone outcomes at age 60 to 64 years, adjusting for baseline dietary pattern Z‐score and other confounders. A consistent PrCaK‐rich dietary pattern was identified within the population, over time. Mean ± SD dietary pattern Z‐scores at age 36 years and age 60 to 64 years were –0.32 ± 0.97 and 2.2 ± 1.5 (women) and –0.35 ± 0.98 and 1.7 ± 1.6 (men), respectively. Mean trajectory in dietary pattern Z‐scores ± SD was 0.07 ± 0.02 units/year. Among women, a 0.02‐SD unit/year higher trajectory in dietary pattern Z‐score over time was associated with higher SA‐BMC (spine 1.40% [95% CI, 0.30 to 2.51]; hip 1.35% [95% CI, 0.48 to 2.23]), and vBMD (radius 1.81% [95% CI, 0.13 to 3.50]) at age 60 to 64 years. No statistically significant associations were found in men. During adulthood, an increasing score for a dietary pattern rich in protein, calcium, and potassium was associated with greater SA‐BMC at fracture‐prone sites in women. This study emphasizes the importance of these nutrients, within the context of the whole diet, to bone health. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

Non-destructive assessment of wrapped mummified animal remains from ancient Egypt using imaging techniques is the most ethically viable manner by which to investigate bundle contents. Bundles studied to date revealed complete and incomplete animal skeletons, multiple individuals (or parts thereof) wrapped together in one bundle, non-skeletal material, organic matter and anomalies of unknown origin. The identification of animal species using imaging alone can be fraught with difficulty, especially in cases in which the skeleton is incomplete and diagnostic elements are lost or significantly damaged. This paper describes the radiographic investigation of a mummy bundle wrapped in the form of a canid, a species closely associated with ancient Egyptian embalming deities. Computed tomography (CT) was performed, and the bundle contents were computer modelled, leading to the production of a laser sintered 3D replica. Imaging identified three skeletal fragments carefully positioned to act as structural support for the bundle; however, radiographic data proved inadequate to enable definitive identification of these elements. 3D printing enabled direct comparison with skeletal reference collections and confirmed that the bones were of human origin. This paper demonstrates that imaging of wrapped animal mummy bundles and 3D printing of unidentified elements or non-skeletal anomalies will assist in their accurate identification in a non-destructive manner.

Vertebral fractures are powerful predictors of future fracture, so, their identification is important to ensure that patients are commenced on appropriate bone protective or bone-enhancing therapy. Risk factors (e.g., low bone mineral density and increasing age) and symptoms (back pain, loss of height) may herald the presence of vertebral fractures, which are usually confirmed by performing spinal radiographs or, increasingly, using vertebral fracture assessment with dual-energy X-ray absorptiometry scanners. However, a large number (30% or more) of vertebral fractures are asymptomatic and do not come to clinical attention. There is, therefore, scope for opportunistic (fortuitous) identification of vertebral fractures from various imaging modalities (radiographs, computed tomography, magnetic resonance imaging, and radionuclide scans) performed for other clinical indications and which include the spine in the field of view, with midline sagittal reformatted images from computed tomography having the greatest potential for such opportunistic detection. Numerous studies confirm this potential for identification but consistently find underreporting of vertebral fractures. So, a valuable opportunity to improve the management of patients at increased risk of future fracture is being squandered. Educational training programs for all clinicians and constant reiteration, stressing the importance of the accurate and clear reporting of vertebral fractures ("you only see what you look for"), can improve the situation, and automated computer-aided diagnostic tools also show promise to solve the problem of this underreporting of vertebral fractures.

We report clinical findings, bone mineral density (BMD) and bone biopsy data in ten children with features of classic idiopathic juvenile osteoporosis (IJO). We also screened the patients for mutations in LRP5 and LRP6. We found low BMD in the lumbar spine, the hip and distal radius. In the spine and distal radius, the reduction in BMD was more marked in the trabecular compartment. Biopsy confirmed that the trabecular compartment is more severely involved with reduction in bone formation and increase in bone resorption. No mutations in LRP5 and LRP6 could be identified. IJO is likely to be a heterogeneous bone disorder, and next-generation genomic sequencing studies may help reveal causative genes.

For quantitative computed tomography (QCT), most relevant variables to discriminate hip fractures were determined. A multivariate analysis showed that trabecular bone mineral density (BMD) of the trochanter with “cortical” thickness of the neck provided better fracture discrimination than total hip integral BMD. A slice-by-slice analysis of the neck or the inclusion of strength-based parameters did not improve fracture discrimination. For QCT of the proximal femur, a large variety of analysis parameters describing bone mineral density, geometry, or strength has been considered. However, in each given study, generally just a small subset was used. The aim of this study was to start with a comprehensive set and then select a best subset of QCT parameters for discrimination of subjects with and without acute osteoporotic hip fractures. The analysis was performed using the population of the European Femur Fracture (EFFECT) study (Bousson et al. J Bone Min Res: Off J Am Soc Bone Min Res 26:881-893, 2011). Fifty-six female control subjects (age 73.2 ± 9.3 years) were compared with 46 female patients (age 80.9 ± 11.1 years) with acute hip fractures. The QCT analysis software MIAF-Femur was used to virtually dissect the proximal femur and analyze more than 1000 parameters, predominantly in the femoral neck. A multivariate best-subset analysis was used to extract the parameters best discriminating hip fractures. All results were adjusted for age, height, and weight differences between the two groups. For the discrimination of all proximal hip fractures as well as for cervical fractures alone, the measurement of neck parameters suffices (area under the curve (AUC) = 0.84). Parameters characterizing bone strength are discriminators of hip fractures; however, in multivariate models, only “cortical” cross-sectional area in the neck center remained as a significant contributor. The combination of one BMD parameter, trabecular BMD of the trochanter, and one geometry parameter, “cortical” thickness of the neck discriminated hip fracture with an AUC value of 0.83 which was significantly better than 0.77 for total femur BMD alone. A comprehensive slice-based analysis of the neck along its axis did not significantly improve hip fracture discrimination. If QCT of the hip is performed, the analysis should include neck and trochanter. In particular, for fractures of any type, a comprehensive slice-based analysis of the neck along its axis did not significantly improve hip fracture discrimination nor did the inclusion of strength-related parameters other than “cortical” area or thickness. One BMD and one geometry parameter, in this study, the combination of trabecular BMD of the trochanter and of “cortical” thickness of the neck resulted in significant hip fracture discrimination.

Background Fractures are associated with mortality and disability and low bone mineral density (BMD) is a known predictor of fracture risk. Research has found an association between cognitive impairment and increased risk of fracture and one possible mechanism is via low BMD. Existing studies have examined BMD as a predictor of cognitive performance. However, it has been suggested that this association might operate in the reverse direction. The MRC National Survey of Health and Development provides a unique opportunity to investigate the associations of cognitive function in adolescence and midlife with bone health at age 60–64. Methods The sample consisted of 658 men and 697 women with pQCT derived measures of trabecular, cortical and total vBMD, distal cross-sectional area (CSA), CSA of the diaphysis and the medullary cavity (medullary CSA), and polar strength strain index (SSI). Cognitive performance was measured using an overall score of general cognitive ability at age 15, and memory and reading ability tasks at age 53. A series of hierarchical multiple regression analyses were performed for each pQCT measure which were adjusted for body size, smoking and socio-economic position. Results For men, when cognition at age 15 and 53 were independently entered in unadjusted and body size adjusted models, both were found to be negatively associated with diaphysis, medullary and distal CSA and SSI, and positively associated with cortical, trabecular and total vBMD. When cognition at age 15 and 53 were mutually adjusted, only cognition at age 15 remained associated with most of the bone outcomes. For example, after adjusting for body size and cognition at 53, 1 point increase in cognition at age 15 was associated with a 4.3% (95% CI −8.3%, −0.3%; p = 0.03) lower Medullary CSA and a 3.8% (95% CI 1.1%, 6.5%; p = 0.006) greater trabecular vBMD. For women, although there was some evidence of associations in unadjusted models, these were fully attenuated once body size was adjusted for. Discussion The associations of cognition in adolescence and midlife with bone health at 60–64 are different for men and women. For men, lower cognitive performance at age 15 and 53 is associated with greater bone size and strength and less bone density at 60–64. For women, it appears that other variables may have a key role in this association. Cognitive performance in early life is associated with bone health in later life and further studies should explore the different underlying mechanisms for men and women.