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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

We aimed to examine whether back pain across adulthood was associated with spine shape at age 60–64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60–64 years. Cumulative exposure to back pain was then derived by counting the number of ages at which back pain was reported. Statistical shape modelling was used to characterise thoracolumbar spine shape using lateral dual-energy x-ray absorptiometry images which were ascertained at age 60–64 years. Linear regression models were used to test associations of spine shape modes (SM) with: (1) cumulative exposure to back pain; (2) back pain reports during different periods of adulthood. After adjusting for sex, higher cumulative exposure to back pain across adulthood was associated with wedge-shaped L4-5 disc (lower SM4 scores) and smaller disc spaces (higher SM8 scores) in both sexes. In addition, reporting of back pain at ages 53 and/or 60–64 years was associated with smaller L4-5 disc space (lower SM6 scores) in men but not women. These findings suggest that back pain across adulthood may be associated with specific variations in spine shapes in early old age.

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.

The aim of this study was to determine whether bone turnover markers (BTMs) predict changes in areal bone mineral density (aBMD) in middle-aged and elderly European men. Older men with high bone turnover are at a higher risk of accelerated hip bone loss, but the clinical utility of BTMs in individuals is limited. Prospective studies on the value of BTMs to predict changes in aBMD in men are few and conflicting. The aim of this study was to determine whether BTMs predict changes in aBMD in middle-aged and elderly European men. In 487 men aged 40–79 years from the European Male Ageing Study (EMAS), BTMs were assessed at baseline and dual-energy X-ray absorptiometry (DXA) at the lumbar spine (LS), femoral neck (FN) and total hip (TH) was performed at baseline and after a mean follow-up of 4.3 years. The mean aBMD decreased by 0.32 %/year at FN and 0.22 %/year at TH and increased by 0.32 %/year at LS. Higher baseline levels of β C-terminal cross-linked telopeptide (β-CTX) and N-terminal propeptide of type I procollagen (PINP) were significantly associated with higher loss of hip aBMD in the whole cohort and men aged 60–79 years. These associations remained significant after adjustment for age, centre and body mass index (BMI). Men aged 60–79 years with β-CTX in the upper quintile were more likely of being in the upper quintile of annual percentage (%) aBMD loss at FN (OR = 4.27; 95% CI = 2.09–8.73) and TH (OR = 3.73; 95% CI = 1.84–7.57). The positive predictive value (PPV) was 46 % at both hip sites. Older men with high bone turnover have a higher risk of accelerated hip bone loss, but the PPV is low. BTMs are therefore unlikely to be of clinical utility in predicting accelerated hip bone loss in individual subjects.

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.

ObjectiveTo assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men.DesignA cross-sectional population-based survey.MethodsMen aged 40–79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β C-terminal cross-linked telopeptide (β-cTX)), total testosterone, total oestradiol (E2), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres.ResultsA total of 3120, mean age 59.9 years (s.d.=11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E2were negatively associated with β-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both β-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine.ConclusionsE2, SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues.

Objective GHD adults exhibit a number of adverse surrogate markers of vascular risk culminating in excess vascular morbidity and mortality. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of a number of vascular morbidities. Furthermore, serum levels decrease following GH replacement in GHD adults, though it remains unclear if levels are significantly elevated in untreated individuals. Design A cross-sectional case–control study. Methods We measured fasting serum VEGF, MMP2, and MMP9 in 27 patients with GHD, 24 with partial GHD (GHI), and 25 sex- and age-matched controls. Results GHD (483 ± 334 vs 326 ± 180 ng/l, P = 0.04), but not GHI (354 ± 192 vs 326 ± 180 ng/l, P = n/s) adults had significantly elevated VEGF levels compared with controls. Neither MMP2, nor MMP9 levels were elevated in the patient groups. Serum VEGF levels correlated positively with LDL-cholesterol (R = 0.34, P = 0.004) and serum MMP9 values (R = 0.36, P = 0.002), and negatively with IGF-I values, however, no correlation was observed with MMP2. Multiple regression analysis with VEGF levels as the dependent variable, and age, gender, % fat mass, LDL-C, insulin and IGF-I as independent variables revealed VEGF levels to be dependent on LDL-C alone (P = 0.003, R = 0.36). Conclusion GHD adults have elevated VEGF levels, which correlate with MMP9 levels. Both VEGF and MMP9 are associated with vascular pathologies and may provide insight in to the pathophysiological mechanisms underlying the increased vascular morbidity and mortality observed in GHD adults.

Background This ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial sub-study examined the effects of anastrozole and tamoxifen on bone mineral density (BMD) following 5 years of treatment. Patients and methods Lumbar spine and total hip BMD were assessed at years 6 and 7 in a total of 71 eligible patients. In total, 50 patients had evaluable data. Results Following anastrozole treatment, the lumbar spine median BMD increased by 2.35% (P = 0.04) and 4.02% (P = 0.0004) at years 6 and 7, while total hip median BMD increased by 0.71% (P = 0.3) and 0.5% (P = 0.8). After tamoxifen treatment, lumbar spine median BMD decreased by 0.79% (P = 0.2) and 0.30% (P = 0.9) at years 6 and 7, while total hip median BMD decreased by 2.09% (P = 0.0003) and 2.52% (P = 0.0002). Patients with a normal BMD or who were osteopenic at 5 years did not become osteoporotic. Conclusions Anastrozole treatment-related bone loss did not continue into the off-treatment follow-up period. The recovery in lumbar spine BMD and absence of further loss at the hip is consistent with the reduction in the annual rate of fracture observed after treatment cessation in the main ATAC trial.

Objectives. To determine the influence of disease-related variables on hand cortical bone loss in women with early inflammatory arthritis (IA), and whether hand cortical bone mass predicts subsequent joint damage. Method. Adults aged >/=16 years with recent onset of IA were recruited to the Norfolk Arthritis Register between 1990 and 1998, and followed prospectively. At baseline, patients had their joints examined for swelling and tenderness and had CRP and disease activity 28-joint assessment score (DAS-28) measured. Radiographs of the hands were performed in a subgroup of patients at Year 1 and at follow-up, which were assessed using digital X-ray radiogrammetry (DXR). They were also evaluated for the presence of erosions using Larsen's method. Linear mixed models were used to investigate whether disease-related factors predicted change in DXR-areal bone mineral density (BMD(a)). We also evaluated whether DXR-BMD(a) predicted the subsequent occurrence of erosive disease. Results. Two hundred and four women, mean (s.d.) age 55.1 (14.0) years, were included. Median follow-up between radiographs was 4 years. The mean within-subject change in BMD(a) was 0.024 g/cm(2) equivalent to 1% decline per year. After adjustment for age, height and weight, compared with those within the lower tertile for CRP, those in the upper tertile had greater subsequent loss of bone. This was true also for DAS-28 and Larsen score. Among those without erosions on the initial radiograph (121), DXR-BMD(a) at baseline did not predict the new occurrence of erosions. Conclusion. Increased disease activity and severity are associated with accelerated bone loss. However, lower BMD(a) did not predict the new occurrence of erosive disease

Metacarpal morphometry and radiogrammetry are the oldest methods for quantitative assessment of the skeleton. The historical aspects of these measurements are reviewed. Although they were inexpensive and widely available and provided useful research and epidemiologic information, they were labor intensive and imprecise. They were replaced with the current established methods of bone mineral densitometry. With the application of modern computer vision techniques, metacarpal morphometric analysis has been rejuvenated, with improvement in precision and evidence that the method can be applied to studies in adults and children. Evidence for limited normal reference data and the ability to predict future fractures in osteoporosis and reflect activity and predict outcomes in rheumatoid arthritis are presented.

The influence of sex steroids on calcaneal quantitative ultrasound (QUS) parameters was assessed in a population sample of middle-aged and elderly European men. Higher free and total E(2) though not testosterone, were independently associated with higher QUS parameters.The aim of this study was to investigate the association between QUS parameters and sex steroids in middle-aged and elderly European men.Three thousand one hundred forty-one men aged between 40 and 79 years were recruited from eight European centres for participation in a study of male ageing: the European Male Ageing Study. Subjects were invited by letter to attend for an interviewer-administered questionnaire, blood sample and QUS of the calcaneus (Hologic-SAHARA). Blood was assessed for sex steroids including oestradiol (E(2)), testosterone (T), free and bio-available E(2) and T and sex hormone binding globulin (SHBG).Serum total T was not associated with any of the QUS parameters. Free T and both free and total E(2) were positively related to all QUS readings, while SHBG concentrations were negatively associated. These relationships were observed in both older and younger (60 years) men. In a multivariate model, after adjustment for age, centre, height, weight, physical activity levels and smoking, free E(2) and SHBG, though not free T, remained independently associated with the QUS parameters. After further adjustment for IGF-1, however, the association with SHBG became non-significant.Higher free and total E(2) are associated with bone health not only among the elderly but also middle-aged European men.

Quantitative computed tomography (QCT) was introduced in the mid 1970s. The technique is most commonly applied to 2D slices in the lumbar spine to measure trabecular bone mineral density (BMD; mg/cm(3)). Although not as widely utilized as dual-energy X-ray absortiometry (DXA) QCT has some advantages when studying the skeleton (separate measures of cortical and trabecular BMD; measurement of volumetric, as opposed to 'areal' DXA-BMDa, so not size dependent; geometric and structural parameters obtained which contribute to bone strength). A limitation is that the World Health Organisation (WHO) definition of osteoporosis in terms of bone densitometry (T score -2.5 or below using DXA) is not applicable. QCT can be performed on conventional body CT scanners, or at peripheral sites (radius, tibia) using smaller, less expensive dedicated peripheral CT scanners (pQCT). Although the ionising radiation dose of spinal QCT is higher than for DXA, the dose compares favorably with those of other radiographic procedures (spinal radiographs) performed in patients suspected of having osteoporosis. The radiation dose from peripheral QCT scanners is negligible. Technical developments in CT (spiral multi-detector CT; improved spatial resolution) allow rapid acquisition of 3D volume images which enable QCT to be applied to the clinically important site of the proximal femur, more sophisticated analysis of cortical and trabecular bone, the imaging of trabecular structure and the application of finite element analysis (FEA). Such research studies contribute importantly to the understanding of bone growth and development, the effect of disease and treatment on the skeleton and the biomechanics of bone strength and fracture.

Context: There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied. Objective: Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force. Design: This was a cross-sectional study. Setting: The study was community based in a secondary school. Participants: A total of 99 post-menarchal 12- to 14-yr-old females was included in the study. Main Outcome Measures: Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured. Results: Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5–88.5) and PTH 3.7 pmol/liter (range 0.47–26.2). Afte...

Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle-aged and elderly European men. Men 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging Study (EMAS). Polymorphisms were genotyped in AR, ESR1, ESR2, CYP19A1, CYP17A1, SHBG, SRD5A2, LHB, and LHCGR. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 +/- 11.1 (SD) yr were included in the analysis. Their mean BUA was 80.0 +/- 18.9 dB/Mhz, SOS was 1550.2 +/- 34.1 m/s, and BMD was 0.542 +/- 0.141 g/cm(2). Significant associations were observed between multiple SNPs in a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (beta =-0.016, p = -0.005) and homozygotes (beta = -0.029, p = 0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in AR and SNPs in CYP17A1, LHCGR, and ESR1. Our data confirm evidence of association between bone QUS parameters and polymorphisms in CYP19A1, as well as modest associations with polymorphisms in CYP17A1, ESR1, LHCGR, and AR in a population sample of European men; this supports a role for genetically determined sex hormone actions in influencing male bone health.

The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive.The aim was to investigate the relationships between health status, various reproductive hormones, and the AR CAG repeat length.We conducted a multinational prospective cohort observational study with cross-sectional baseline data.This was a population survey of community-dwelling men.Men (40-79 yr old; n = 3369) were randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2878 men.We measured the correlations of the CAG repeat length with selected endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action.Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free, and bioavailable levels of testosterone (T) and estradiol. FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions.The AR CAG repeat length correlates significantly with serum T and estradiol of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or nearly totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions after aromatization of the higher T levels.

Purpose The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (median follow-up, 68 months) has shown that adjuvant anastrozole has superior efficacy and better tolerability than tamoxifen. However, anastrozole reduces circulating estrogen, and low estradiol levels are associated with decreased bone mineral density (BMD) and increased fracture risk. It is therefore important to understand the effects of long-term aromatase inhibitor therapy on BMD. Patients and Methods This prospective substudy of the ATAC trial assessed BMD changes in postmenopausal women with invasive primary breast cancer receiving anastrozole (1 mg/d) or tamoxifen (20 mg/d) as adjuvant therapy for 5 years. Lumbar spine and total hip BMD were assessed at baseline and after 1, 2, and 5 years. Results One hundred ninety-seven women from the monotherapy arms of the ATAC trial were recruited onto the bone substudy, and 108 were included in the primary analysis. Among anastrozole-treated patients, there was a decrease in median BMD from baseline to 5 years in lumbar spine (−6.08%) and total hip (−7.24%) compared with the tamoxifen group (lumbar spine, +2.77%; total hip, +0.74%). No patients with normal BMD at baseline became osteoporotic at 5 years. Conclusion Anastrozole is associated with accelerated bone loss over the 5-year treatment period. However, although patients with pre-existing osteopenia are likely to require monitoring and bone-protection strategies, patients with normal BMD would not appear to require monitoring beyond the recommendation for healthy postmenopausal women. The effect of anastrozole on bone should be weighed against its superior efficacy and better tolerability profile versus tamoxifen in the main ATAC trial.

Objectives: To determine the diagnostic accuracy of mandibular and maxillary bone densityin detecting osteoporosis using receiver operating characteristic (ROC) analysis.Methods: 671 women between 45 years and 70 years of age underwent dual energy X-rayabsorptiometry (DXA) of the hip and lumbar spine. This was the gold standard for diagnosing osteoporosis. Intraoral radiography of the upper and lower right premolar regionwas performed, using an aluminium wedge as a densitometric reference. Jaw bone densitywas determined using dedicated software. Observer differences and ROC curves wereanalysed.Results: For detecting osteoporosis using jaw bone density, the area under the ROC curve(Az) was 0.705. For separate analysis of mandibular and maxillary films, sensitivity variedfrom 33.9% to 38.7% and specificity from 83.5% to 85.3% when using a threshold of 4.3 mm Al equivalent.Conclusions: Density of the premolar region reaches a fair diagnostic accuracy, which might improve when including additional factors in the analysis and refining the densitometric tool.