Abstract Abnormal development of bone or cartilage in children causes many alterations in anatomy and physiology. With over 400 distinct syndromes and subtypes, it is notable that there is an incidence of 15.7 per 100,000 live births of disproportionate shortening of limbs or trunks. Down syndrome is the most common genetic disorder, with other disorders, such as achondroplasia, Klippel-Feil syndrome, Marfan syndrome, osteogenesis imperfecta, and Morquio syndrome, also being relatively common. These syndromes can present anesthetic challenges, such as difficulty with intubation, proper positioning, and management of cardiopulmonary comorbidities. These issues should be anticipated when determining an anesthetic plan for these children.

• This is a pre-copyedited, author-produced version of an article accepted for publication in International Journal of Epidemiology following peer review. The version of record COLE, T.J. ... et al, 2016. Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life: the Medical Research Council (MRC) National Survey of Health and Development. International Journal of Epidemiology, 45(4), pp.1125-1134 is available online at: http://dx.doi.org/10.1093/ije/dyw134.

Background Osteoporotic fractures are a global concern due to associated patient mortality, morbidity and health service expenditure. Optimal care provided by non-physician health professionals, such as dieticians, nurses, occupational therapists, pharmacists and physiotherapists, to adults at high risk of primary or secondary osteoporotic fracture, is integral in the prevention and management of minimal trauma fracture, but may not be sufficiently realised in all European countries. To address this, a commissioned task force has developed the first collaborative EULAR points to consider/recommendations for non-physician health professionals in the prevention and management of osteoporotic fractures, underpinned by a systematic literature review (SLR). Objectives To identify and review the scientific literature to inform the development of evidence-based EULAR points to consider/recommendations for non-physician health professionals in the prevention and management of osteoporotic fracture. Methods A SLR for each of eight clinical questions that were previously formulated and consensually agreed by the task force members was undertaken by a research fellow (NW), with guidance from the task force convenors and the methodologist. Four electronic databases (Medline, Embase, Cinahl and PubMed) were searched over the period 13th - 31 st October 2017. The search strategies combined MeSH terms and keywords to identify studies related to two key concepts: (i) adults≥50 years of age at high risk of primary or secondary osteoporotic fracture and (ii) interventions delivered by non-physician health professionals to prevent, treat and manage osteoporotic fractures. Exclusion criteria included articles not in English and without online access. Evidence was categorised using the Oxford Centre for Evidence-based Medicine Levels of Evidence. For critical appraisal of systematic reviews, AMSTAR 2 was used. Risk of bias was assessed by the Cochrane Collaboration’s tool. Results The eight primary searches returned a total of 15 917 citations; duplicates were removed and the remaining 11 195 citations screened for relevance by title, abstract, design and year of publication (recently published reviews and/or RCTs were prioritised). Thirty-two studies were finally selected. Overall confidence in the findings of included systematic reviews (n=13) ranged from low to high. Risk of bias also varied across other included studies. Strongest evidence of benefit was found for exercise in the management of osteoporotic fracture [level 1a]. Conclusions There is a lack of high quality evidence for the role of health professionals in the prevention and management of adults at high risk of primary or secondary osteoporotic fracture. We recommend the instigation of an education and research agenda for non-physician health professionals. References [1] Shea B, Reeves B, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ2017;358:j4008. [2] Higgins J, Altman D, Gøtzsche P, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ2011;343:d5928. Acknowledgements We thank Vicky Fenerty, research engagement librarian at the University of Southampton for her advice. Disclosure of Interest None declared

Background Interventions delivered by non-physician health professionals, such as physiotherapists, occupational therapists and nurses play an important role in effective management of patients with osteopenia or osteoporosis. Objectives To establish EULAR Points to Consider/Recommendations for the prevention and management of osteoporotic fractures by non-physician health professionals. Methods Points to consider/recommendations were developed according to EULAR standard procedures1 using six stages: i) establishment of an international expert panel/task force including patients, rheumatologists, orthopaedic surgeons and health professionals; ii) a first Delphi-round to set up clinical questions; iii) a literature review; iv) a task force meeting to review the results of the literature search and to formulate points to consider/recommendations; v) development of consensus and assessment of the level of agreement with the points to consider/recommendations using second Delphi round; vi) a field test. Results Eight clinical questions and two overarching principles were formulated, subject to the literature search (the clinical questions only) and discussed and refined during the task force meeting. The two overarching principles focused on the importance of shared decision making between patients and professionals and the involvement of different health professionals. Two clinical questions were merged and the task force finally agreed on seven recommendations/points to consider: 1) Health professionals should start with fall risk evaluation in patients at risk of primary or secondary fracture. Patients with high risk should be evaluated by a health professional using multi-component screening, or referred to another health professional competent in multi-component screening. 2) Health professionals should ensure that after osteoporotic fracture, patients are given opportunities to participate in adequate exercise and are supported in adequate nutritional intake. Calcium and vitamin D intake should be discussed with the patients. 3) Smoking and overuse of alcohol should be discouraged. 4) Tailored multicomponent interventions including, for example: exercises, environmental adaptations, nutrition, life-style and education, should be offered to patients at high risk of primary osteoporotic fracture and/or high risk of falls. 5) Health professionals should be included in Fracture Liaison Services (FLS) and/or a coordinated, multidisciplinary post-fracture prevention program. Patients with fragility fractures should be referred to a FLS or an adequate, coordinated, multidisciplinary post-fracture prevention program. 6) Health professionals should address, monitor and support medication adherence in a structured follow up. 7) Health professionals should identify patients at risk of bone fragility, ensure they are offered opportunities for adequate treatment, and address bone fragility through patient education. Conclusions These points to consider/recommendations should be applied by health professionals in the prevention and management of osteoporotic fracture to ensure high quality care. Reference [1] van der Heijde D, Aletaha D, Carmona L, et al. 2014Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations. Ann Rheum Dis2015;74(1):8–13. Disclosure of Interest None declared

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 < 0.001). At their 2 year assessment, 5 DAILY and 10 INTERMITTENT boys were non-ambulant. DAILY boys had more VFs than INTERMITTENT boys (10 versus 2; chi(2) p = 0.008). BMAD SDS remained unchanged between groups. TBLH and radius BMD declined significantly but the rate of loss was not different. In conclusion, there was a trend for more boys on daily GCs to remain ambulant but at the cost of more VFs, greater adiposity and markedly diminished growth. In contrast, boys on intermittent GCs had fewer vertebral fractures but there was a trend for more boys to loose independent ambulation.

Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40–79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline.

This study explores the association between cognitive ability in childhood and midlife and bone health outcomes in early old age; and the relationships of these bone measures with contemporaneous and subsequent cognitive ability in the MRC National Survey of Health and Development (NSHD). This British birth cohort assessed areal and volumetric bone mineral density (aBMD and vBMD) at age 60-64, derived from peripheral quantitative computed tomography and dual-energy X-ray absorptiometry, and cognitive performance from childhood to age 69, among 866 women and 792 men. Cognitive performance at age 15 was assessed using tests of verbal and non-verbal ability, and mathematics; and memory and search speed tasks were administered at ages 53, 60-64, and 69. Covariates included body size, pubertal timing, smoking, leisure time physical activity, socioeconomic circumstances and menopause timing. Multiple linear regression analyses showed that higher childhood cognitive ability was associated with higher hip aBMD, in women, and greater cortical and trabecular vBMD, in men. For women, there were positive associations between hip aBMD and total vBMD, and contemporaneous cognitive ability with associations also extending to subsequent cognitive ability for total vBMD. For men, some associations with trabecular and total vBMD emerged at ages 60-64 and 69 but only after adjusting for education, occupational class and health behaviors. Our findings highlight that higher cognitive ability in childhood is associated with BMD in early old age and these associations might be explained by social and behavioral pathways. The results suggest that individuals with greater cognitive ability in early life are more likely to engage in healthy behaviors (e.g., leisure time physical activity) in adulthood, which in turn are associated with greater BMD later in life. Associations between bone health and cognitive performance should be considered within a life course framework; and the potential role of smoking and physical activity should be addressed when advising adults at high future risk of osteoporosis and fracture.

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: A10-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.

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.

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 40years 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<0.001). At the tibia and radius diaphysis, Black men had larger bones with thicker cortices and greater bending strength than the other groups. There were fewer differences between White and South Asian men. At the metaphysis, South Asian men had smaller bones (p=0.02) and lower trabecular vBMD at the tibia (p=0.003). At the diaphysis, after size-correction, South Asian men had similar sized bones but thinner cortices than White men; measures of strength were not broadly reduced in the South Asian men. Combining pQCT and DXA measurements has given insight into differences in bone phenotype in men from different ethnic backgrounds. Understanding such differences is important in understanding the aetiology of male osteoporosis.

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits.

Purpose: Spine shape varies widely between individuals and is important for load bearing, yet associations with markers of health and disease have not been explored. The purpose of this pilot study was to characterise thoracolumbar spine shape in a sample of early old-age adults from the Medical Research Council National Survey of Health and Development (NSHD) and explore how it varies with anthropometric measures, bone mineral density (BMD) and sex. Methods: Using a pilot sample of 200 individuals in the NSHD birth cohort, all born in a single week in 1946, data included height, weight, body mass index (BMI), and spine bone mineral density (BMD) acquired at 60–64 years. Sagittal spine shape between the tenth thoracic and fifth lumbar vertebrae was described using an 89 point statistical shape model (SSM) on lateral dual-energy x-ray absorptiometry (DXA) images. Points entered into the SSM identified the average spine shape and independent modes of variation in shape, using principal components analysis. Mode scores quantified deviations from the mean shape. The first 10 modes explained 88% of variation in shape and were chosen for further analysis. Modes scores were tested for normality using the Shapiro-Wilk test and the Mann-Whitney test was used to compare the median difference between men and women. Associations between potential predictive factors and shape modes were tested using Spearman’s rank correlation. Results: The sample consisted of 110 men and 90 women with a median (interquartile range) age of 63.6 (62.8–64.2) years and BMI of 27 kg/m2 (24.5–30.5). Men were significantly taller and heavier (14 cm, 13 kg, respectively) compared with women. Similar to previous studies the first two modes described the total amount (M1) and distribution (M2) of spine curvature while M3 accounted for vertebral width. Sex differences existed in 5/10 modes (P<0.01). Women were more likely to have a snaking curvature (-M2) whilst men had an evenly distributed curvature (+M2) (P<0.001) and wider vertebral bodies (-M3, P<0.0001). Women had caudally increasing vertebral width and narrower L4/L5 disc space (+M6, P<0.0001) and men had narrower thoracic vertebrae (+M8, P<0.01) with a flatter curve (+M9, P<0.01). Correlations with height, weight and BMI varied by sex. Modes 2 and 6 (Fig. 1) were positively correlated with BMD in men alone (r=0.29 and 0.26, respectively). In women only, modes 4 and 5 negatively correlated with BMD (r=−0.28 and −0.20, respectively) while M3 correlated positively with height (r=0.27) and negatively with BMI (r=−0.21, Fig. 1). Scores for M9 increased with increasing weight (r=0.32) and BMI in men (r=0.31) but decreased with greater BMD in women (r=−0.24). Conclusions: In this sample of early old-age adults, sex-differences were observed in the distribution of spinal curvature and vertebral width rather than overall curvature. Furthermore, associations between spine shape, BMD and body size varied by sex. Greater BMD was related to snakier curvatures with distinct thoracic kyphosis and lumbar lordosis in women but an even overall curvature in men. These sex differences have not been explored in detail before but may be related to morphologic variations in other joints, which requires further investigation. These data will enable prospective studies of associations between spinal morphology and incident osteoarthritis.

Purpose: Hip shape has been shown to vary in osteoarthritis and osteoporosis but there is little evidence for associations with other markers of health and disease. The purpose of this pilot study was to characterise hip shape in a sample of early old-age adults from the Medical Research Council National Survey of Health and Development (NSHD) and explore how it varies with anthropometric measures, bone mineral density (BMD) and sex. Methods: Using a pilot sample of 200 individuals in the NSHD birth cohort, all born in a single week in 1946, data included height, weight, body mass index (BMI), and hip bone mineral density (BMD) acquired at 60–64 years. Hip shape was described using a 68 point template on dual energy absorptiometry (DXA) images. Points were entered into a statistical shape model using the Shape software (University of Aberdeen), which identified the mean hip shape and independent modes of variation in the shape, using principal components analysis. Modes scores quantified as the deviation from the mean shape (mean = 0). The first 15 modes (M1-M15) described 86.8% of the total variation of shape within the model, in decreasing order. Modes 1–15 were included in further analysis. Modes scores were tested for normality using the Shapiro-Wilk test and the Mann-Whitney test was used to compare the median difference between males and females. Spearman's rank correlation was used to investigate the association between potential predictive factors and shape modes. Results: The sample consisted of 90 males and 110 females with a median age of 63.6 (62.8–64.2) years and median BMI of 27.3 (24.5–30.5) kg/m2. Males were significantly taller and heavier than women. In this sample there were significant differences between the sexes in 6 of the 15 analysed modes. Comparisons of hip shape between males and females revealed a significant difference with males having a higher M1 (P=0.017) and M4 (P=0.004) scores, both of which were associated with flattening of the femoral head and presence of osteophytes, and lower M9 scores reflecting flattening of the femoral head and neck (P<0.0001; Fig. 1). M11 scores were associated with increased acetabular coverage and higher in females (P=0.0137). Associations between shape and height, weight, BMI and BMD varied greatly between men and women. In the hip, M1 was negatively correlated with height and BMD in women, but not men, whilst M9 was positively correlated with height and BMD in men, but not women. Modes 15 was correlated with weight and BMI in men. The only mode which showed significant correlations in both sexes was M5, though this was positively correlated with weight and BMI in women and Total hip BMD in men. Modes 9, 11 and 12 were all correlated with BMD in men. Conclusions: In this sample of adults entering early old-age, sex differences were observed in the width of the femoral neck, femoral neck/head curvature and migration of the femoral head. Correlations between hip shape, BMD and body size varied by sex. Greater BMD was associated with a more compact hip shape in women and being a taller man was associated with changes in the curvature of the femoral head and neck.

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. (c) 2015 Elsevier Ltd. All rights reserved.