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Objective: To examine the extent to which geometric parameters derived from dual-energy x-ray absorptiometry (DXA) scans in the UK Biobank study are related to hip osteoarthritis (HOA) independently of sex, age and body size., Design: Femoral neck width (FNW), diameter of the femoral head (DFH) and hip axis length (HAL) were derived automatically from left hip DXA scans in UK Biobank using outline points placed around the hip by a machine-learning program. Correlations were calculated between geometric parameters, age, height, and weight. Logistic regression was used to examine the relationship of geometric parameters with radiographic HOA, hospital diagnosed HOA (HESOA), and Cox proportional hazards model to evaluate the relationship with total hip replacement (THR). Analyses were adjusted for sex, age, height, weight, and geometric parameters., Results: The study consisted of 40,312 participants. In age and sex-adjusted analyses, FNW, HAL and DFH were related to increased risk of radiographic HOA. In a model adjusted for age, sex, height, weight and other geometric parameters, both FNW and HAL retained independent relationships with radiographic HOA [FNW: odds ratios 2.38 (2.18-2.59), HAL: 1.25 (1.15-1.36)], while DFH was now protective [0.55 (0.50-0.61)]. Only FNW was independently related to HESOA [2.20 (1.80-2.68)] and THR [hazard ratios 2.51 (1.89-3.32)]., Conclusion: Greater FNW and HAL were independently related to an increased risk of radiographic HOA, whereas greater DFH appeared to be protective. Greater FNW was independently associated with HESOA and THR. These results suggest that DXA-derived geometric parameters, particularly FNW, could help determine HOA and THR risk., Competing Interests: Declaration of Competing Interest TC & CL have a patent image processing apparatus and method for fitting a deformable shape model to an image using random forest regression voting. This is licensed with royalties to Optasia Medical. NH reports consultancy fees and honoraria from UCB, Amgen, Kyowa Kirin, Thornton Ross, Consilient., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aimed to cross-calibrate body composition measures from the GE Lunar Prodigy and GE Lunar iDXA in a cohort of young children. 28 children (mean age 3.4 years) were measured on the iDXA followed by the Prodigy. Prodigy scans were subsequently reanalysed using enCORE v17 enhanced analysis ("Prodigy enhanced"). Body composition parameters were compared across three evaluation methods (Prodigy, Prodigy enhanced, iDXA), and adjustment equations were developed. There were differences in the three evaluation methods for all body composition parameters. Body fat percentage (%BF) from the iDXA was approximately 1.5-fold greater than the Prodigy, whereas bone mineral density (BMD) was approximately 20% lower. Reanalysis of Prodigy scans with enhanced software attenuated these differences (%BF: - 5.2% [95% CI - 3.5, - 6.8]; and BMD: 1.0% [95% CI 0.0, 1.9]), although significant differences remained for all parameters except total body less head (TBLH) total mass and TBLH BMD, and some regional estimates. There were large differences between the Prodigy and iDXA, with these differences related both to scan resolution and software. Reanalysis of Prodigy scans with enhanced analysis resulted in body composition values much closer to those obtained on the iDXA, although differences remained. As manufacturers update models and software, researchers and clinicians need to be aware of the impact this may have on the longitudinal assessment of body composition, as results may not be comparable across devices and software versions., (© 2022. The Author(s).)

Aim: To investigate the associations between indices of bone health in childhood and corresponding parental measures., Methods: The Southampton Women's Survey characterised 12,583 non-pregnant women aged 20-34 years; 3158 subsequently had singleton live births. In a subset, dual-energy X-ray absorptiometry (DXA) measurements of bone area (BA), bone mineral content (BMC) and areal bone mineral density (aBMD) lumbar spine and total hip were obtained in the parent/offspring (aged 8-9 years) trios. Another subset of children (aged 6-7 years), and their parents, had peripheral quantitative computed tomography (pQCT; 4% and 38% tibia) measures. Using multivariable linear regression we examined relationships between mother/father and offspring, adjusting for parental age, habitual walking speed and education; offspring age and sex; and the corresponding bone measure in the other parent (β-coefficients (95%CI) unit/unit for each bone measure)., Results: Data were available for 260 trios with DXA and 99 with pQCT. There were positive associations for BA, BMC and aBMD between either parent and offspring. Mother-child associations were of greater magnitude than father-child; for example, mother-child aBMD (β = 0.26 g·cm -2 /g·cm -2 (0.21,0.32)) and father-child aBMD (β = 0.16 g·cm -2 /g·cm -2 (0.11,0.21)), P-difference in β = 0.007. In the subset with pQCT there was a positive association for mother-offspring 4% tibial total area (β = 0.33 mm 2 /mm 2 (0.17,0.48)), but little evidence of a father-offspring association (β = -0.06 mm 2 /mm 2 (-0.17,0.06)). In contrast offspring 38% cortical density was more strongly associated with this measure in fathers (β = 0.48 mg·cm -3 /mg·cm -3 (0.15,0.82)) than mothers (β = 0.27 mg·cm -3 /mg·cm -3 (-0.03,0.56)). In general mother-father differences were attenuated by adjustment for height., Conclusions: Whilst offspring bone measures are independently associated with those of either parent, the magnitude of the association is often greater for maternal than paternal relationships. These findings are consistent with an in utero influence on offspring growth but might also reflect genetic and/or epigenetic parent of origin effects., Summary: In an established parent-offspring cohort, associations between parent and offspring bone indices were generally greater in magnitude for mother-offspring than father-offspring relationships., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Osteoporosis is an age-associated disease characterised by low bone mineral density (BMD) and micro-architectural deterioration leading to enhanced fracture risk. Conventional dual-energy X-ray absorptiometry (DXA) analysis has facilitated our understanding of BMD reduction in specific regions of interest (ROIs) within the femur, but cannot resolve spatial BMD patterns nor reflect age-related changes in bone microarchitecture due to its inherent averaging of pixel BMD values into large ROIs. To address these limitations and develop a comprehensive model of involutional bone loss, this paper presents a fully automatic pipeline to build a spatio-temporal atlas of ageing bone in the proximal femur. A new technique, termed DXA region free analysis (DXA RFA), is proposed to eliminate morphological variation between DXA scans by warping each image into a reference template. To construct the atlas, we use unprocessed DXA data from Caucasian women aged 20-97 years participating in three cohort studies in Western Europe ( ,000). A novel calibration procedure, termed quantile matching regression, is proposed to integrate data from different DXA manufacturers. Pixel-wise BMD evolution with ageing was modelled using smooth quantile curves. This technique enables characterisation of spatially-complex BMD change patterns with ageing, visualised using heat-maps. Furthermore, quantile curves plotted at different pixel coordinates showed consistently different rates of bone loss at different regions within the femoral neck. Given the close relationship between spatio-temporal bone loss and osteoporotic fracture, improved understanding of the bone ageing process could lead to enhanced prognostic, preventive and therapeutic strategies for the disease.

Using data from the Hertfordshire cohort study, this study examined the effect of breastfeeding and bottle feeding on adult lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD). The type of infant milk feeding was significantly associated with lumbar spine BMD in males., Introduction: Using data from the Hertfordshire cohort study (HCS), this study aims to examine the effect of infant milk feeding on bone health in later life by comparing the effect of breastfeeding and bottle feeding on lumbar spine and femoral neck BMC and BMD., Methods: Information about infant milk feeding, birth weight (kg) and weight at 1 (kg) was collected by health visitors between 1931 and 1939 in Hertfordshire. BMC and BMD measurements were taken by DXA scan between 1998 and 2004. Linear regression models adjusted for conditional weight at 1, age at DXA scan, sex, adult BMI, smoking behaviour, alcohol consumption, physical activity, dietary calcium, and prudent diet score., Results: Infant milk feeding was significantly associated with lumbar spine BMD (b = - 0.028; 95% CI, - 0.055; - 0.000; p value, 0.047) in males. On average, males who consumed breastmilk alternatives in infancy had lower lumbar spine BMD measurements than those who were fed only breastmilk. These associations remained significant in fully adjusted models. There were no significant associations between infant milk feeding and bone health for females., Conclusions: Significant associations between infant milk feeding and lumbar spine BMD in males indicate that breastmilk may be protective for the bone health of male babies. The evidence presented here underscores the potential lifelong benefits of breastfeeding and may highlight the differences between osteoporotic risk factors for males and females.

In the large community-based SCOOP trial, systematic fracture risk screening using FRAX ® led to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care., Introduction: In the SCreening of Older wOmen for Prevention of fracture (SCOOP) trial, we investigated the effect of the screening intervention on subsequent long-term self-reported adherence to anti-osteoporosis medications (AOM)., Methods: SCOOP was a primary care-based UK multicentre trial of screening for fracture risk. A total of 12,483 women (70-85 years) were randomised to either usual NHS care, or assessment using the FRAX ® tool ± dual-energy X-ray absorptiometry (DXA), with medication recommended for those found to be at high risk of hip fracture. Self-reported AOM use was obtained by postal questionnaires at 6, 12, 24, 36, 48 and 60 months. Analysis was limited to those who initiated AOM during follow-up. Logistic regression was used to explore baseline determinants of adherence (good ≥ 80%; poor < 80%)., Results: The mean (SD) age of participants was 75.6 (4.2) years, with 6233 randomised to screening and 6250 to the control group. Of those participants identified at high fracture risk in the screening group, 38.2% of those on treatment at 6 months were still treated at 60 months, whereas the corresponding figure for the control group was 21.6%. Older age was associated with poorer adherence (OR per year increase in age 0.96 [95% CI 0.93, 0.99], p = 0.01), whereas history of parental hip fracture was associated with greater rate adherence (OR 1.67 [95% CI 1.23, 2.26], p < 0.01)., Conclusions: Systematic fracture risk screening using FRAX ® leads to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care.

We compared bone outcomes in children with breech and cephalic presentation at delivery. Neonatal whole-body bone mineral content (BMC) and area were lower in children with breech presentation. At 4 years, no differences in whole-body or spine measures were found, but hip BMC and area were lower after breech presentation., Introduction: Breech presentation is associated with altered joint shape and hip dysplasias, but effects on bone mineral content (BMC), area (BA) and density (BMD) are unknown., Methods: In the prospective Southampton Women's Survey mother-offspring cohort, whole-body bone outcomes were measured using dual-energy X-ray absorptiometry (DXA) in 1430 offspring, as neonates (mean age 6 days, n = 965, 39 with a breech presentation at birth) and/or at age 4.1 years (n = 999, 39 breech). Hip and spine bone outcomes were also measured at age 4 years., Results: Neonates with breech presentation had 4.2 g lower whole-body BMC (95% CI -7.4 to - 0.9 g, P = 0.012) and 5.9 cm 2 lower BA (- 10.8 to - 1.0 cm 2 , P = 0.019), but BMD was similar between groups (mean difference - 0.007, - 0.016 to 0.002 g/cm 2 , P = 0.146) adjusting for sex, maternal smoking, gestational diabetes, mode of delivery, social class, parity, ethnicity, age at scan, birthweight, gestational age and crown-heel length. There were no associations between breech presentation and whole-body outcomes at age 4 years, but, in similarly adjusted models, regional DXA (not available in infants) showed that breech presentation was associated with lower hip BMC (- 0.51, - 0.98 to - 0.04 g, P = 0.034) and BA (- 0.67, - 1.28 to - 0.07 cm 2 , P = 0.03) but not with BMD (- 0.009, - 0.029 to 0.012 g, P = 0.408), or spine outcomes., Conclusions: These results suggest that breech presentation is associated with lower neonatal whole-body BMC and BA, which may relate to altered prenatal loading in babies occupying a breech position; these differences did not persist into later childhood. Modest differences in 4-year hip BMC and BA require further investigation.

Objective: To assess whether different trajectories of weight gain since birth influence bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age., Study Design: We studied a subsample of 1889 children from the Generation XXI birth cohort who underwent whole-body dual-energy radiograph absorptiometry. Weight trajectories identified through normal mixture modeling for model-based clustering and labeled "normal weight gain," "weight gain during infancy," "weight gain during childhood," and "persistent weight gain" were used. Differences in subtotal BMC, aBMD, and size-corrected BMC (scBMC) at age 7 years according to weight trajectories were estimated through analysis of covariance., Results: Compared with the "normal weight gain" trajectory, children in the remaining trajectories had significantly greater BMC, aBMD, and scBMC at age 7 years, with the strongest associations for "persistent weight gain" (girls [BMC: 674.0 vs 559.8 g, aBMD: 0.677 vs 0.588 g/cm 2 , scBMC: 640.7 vs 577.4 g], boys [BMC: 689.4 vs 580.8 g, aBMD: 0.682 vs 0.611 g/cm 2 , scBMC: 633.0 vs 595.6 g]). After adjustment for current weight, and alternatively for fat and lean mass, children with a "weight gain during childhood" trajectory had greater BMC and aBMD than those with a "normal weight gain" trajectory, although significant differences were restricted to girls (BMC: 601.4 vs 589.2 g, aBMD: 0.618 vs 0.609 g/cm 2 )., Conclusion: Overall, children following a trajectory of persistent weight gain since birth had clearly increased bone mass at 7 years, but weight gain seemed slightly more beneficial when it occurred later rather than on a normal trajectory during the first 7 years of life., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We studied a prospective UK cohort of women aged 20 to 80 years, assessed by dual-energy X-ray absorptiometry (DXA) at baseline. Bone mineral content (BMC) and areal bone mineral density (aBMD), but not bone area (BA), at femoral neck, lumbar spine and the whole body sites were similarly predictive of incident fractures., Background: Low aBMD, measured by DXA, is a well-established risk factor for future fracture, but little is known about the performance characteristics of other DXA measures such as BA and BMC in fracture prediction. We therefore investigated the predictive value of BA, BMC and aBMD for incident fracture in a prospective cohort of UK women., Methods: In this study, 674 women aged 20-80 years, recruited from four GP practices in Southampton, underwent DXA assessment (proximal femur, lumbar spine, total body) between 1991 and 1993. All women were contacted in 1998-1999 with a validated postal questionnaire to collect information on incident fractures and potential confounding factors including medication use. Four hundred forty-three women responded, and all fractures were confirmed by the assessment of images and radiology reports by a research nurse. Cox proportional hazard models were used to explore the risk of incident fracture, and the results are expressed as hazard ratio (HR) per 1 SD decrease in the predictor and 95% CI. Associations were adjusted for age, BMI, alcohol consumption, smoking, HRT, medications and history of fracture., Results: Fifty-five women (12%) reported a fracture. In fully adjusted models, femoral neck BMC and aBMD were similarly predictive of incident fracture. Femoral neck BMC: HR/SD = 1.64 (95%CI: 1.19, 2.26; p = 0.002); femoral neck aBMD: HR/SD = 1.76 (95%CI: 1.19, 2.60; p = 0.005). In contrast, femoral neck BA was not associated with incident fracture, HR/SD = 1.15 (95%CI: 0.88, 1.50; p = 0.32). Similar results were found with bone indices at the lumbar spine and the whole body., Conclusions: In conclusion, BMC and aBMD appear to predict incident fracture with similar HR/SD, even after adjustment for body size. In contrast, BA only weakly predicted the future fracture. These findings support the use of DXA aBMD in fracture risk assessment, but also suggest that factors which specifically influence BMC will have a relevance to the risk of the incident fracture., Competing Interests: EM Curtis, NC Harvey, S D’Angelo, CS Cooper, KA Ward, P Taylor, G Pearson, C Cooper declare no conflicts of interest in relation to this paper.

Summary: A healthy diet positively influences childhood bone health, but how the food environment relates to bone development is unknown. Greater neighbourhood access to fast-food outlets was associated with lower bone mass among infants, while greater access to healthy speciality stores was associated with higher bone mass at 4 years., Introduction: Identifying factors that contribute to optimal childhood bone development could help pinpoint strategies to improve long-term bone health. A healthy diet positively influences bone health from before birth and during childhood. This study addressed a gap in the literature by examining the relationship between residential neighbourhood food environment and bone mass in infants and children., Methods: One thousand one hundred and seven children participating in the Southampton Women's Survey, UK, underwent measurement of bone mineral density (BMD) and bone mineral content (BMC) at birth and 4 and/or 6 years by dual-energy X-ray absorptiometry (DXA). Cross-sectional observational data describing food outlets within the boundary of each participant's neighbourhood were used to derive three measures of the food environment: the counts of fast-food outlets, healthy speciality stores and supermarkets., Results: Neighbourhood exposure to fast-food outlets was associated with lower BMD in infancy (β = -0.23 (z-score): 95% CI -0.38, -0.08) and lower BMC after adjustment for bone area and confounding variables (β = -0.17 (z-score): 95% CI -0.32, -0.02). Increasing neighbourhood exposure to healthy speciality stores was associated with higher BMD at 4 and 6 years (β = 0.16(z-score): 95% CI 0.00, 0.32 and β = 0.13(z-score): 95% CI -0.01, 0.26 respectively). The relationship with BMC after adjustment for bone area and confounding variables was statistically significant at 4 years, but not at 6 years., Conclusions: The neighbourhood food environment that pregnant mothers and young children are exposed may affect bone development during early childhood. If confirmed in future studies, action to reduce access to fast-food outlets could have benefits for childhood development and long-term bone health.

Unlabelled: In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate geometric, volumetric and microstructural parameters at the distal radius and at the distal tibia in participants with ischaemic heart disease. We found that, compared with participants without ischaemic heart disease, they had substantially lower cortical volumetric bone mineral density (BMD) at the distal radius., Introduction: HR-pQCT captures novel aspects of bone geometry and volumetric bone mineral density (vBMD) and offers the ability to measure bone microarchitecture, but data relating measures obtained from this technique in patients with ischemic heart disease (IHD) are lacking., Methods: Here, we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between measures obtained from HR-pQCT of distal radius and distal tibia in 350 participants (184 men and 166 women) aged 71.5-80.5 years with or without IHD (e.g. heart attack, angina or heart failure; n = 75 and n = 275, respectively)., Results: Analyses for all participants (men and women together) revealed that cortical vBMD (Ct.vBMD) was lower (p < 0.001) and cortical thickness (Ct.th) was not different (p = 0.519), whereas cortical porosity (Ct.Po) was higher (p = 0.016) in participants with IHD at the distal radius. Moreover, trabecular microarchitectural parameters were not significantly different in patients with IHD (p > 0.05 for all). Adjustment for a priori confounders (age, gender, body mass index, smoking status, alcohol consumption, high blood pressure and diabetes mellitus) did not materially affect the relationship described for Ct.vBMD (p = 0.002), but differences in Ct.Po were attenuated. Analyses in men alone revealed that only Ct.vBMD was lower at the distal radius in participants with IHD with and without adjustment for a priori confounders (p = 0.0002 and p = 0.004, respectively), whereas no statistical differences were found in women, although patterns of differences were similar in both sexes. Moreover, no association was found between IHD and bone parameters at the distal tibia either in men or women., Conclusions: We have demonstrated that IHD is associated with lower Ct.vBMD of the distal radius.

During growth, severe vitamin D deficiency in childhood can result in symptomatic hypocalcaemia and rickets. Despite the suggestion from some studies of a secular increase in the incidence of rickets, this observation may be driven more by changes in population demographics than a true alteration to age, sex and ethnicity-specific incidence rates; indeed, rickets remains uncommon overall and is rarely seen in fair-skinned children. Additionally, the impact of less severe vitamin D deficiency and insufficiency has received much interest in recent years, and in this review, we consider the evidence relating vitamin D status to fracture risk and bone mineral density (BMD) in childhood and adolescence. We conclude that there is insufficient evidence to support the suggestion that low serum 25-hydroxyvitamin D [25(OH)D] increases childhood fracture risk. Overall, the relationship between 25(OH)D and BMD is inconsistent across studies and across skeletal sites within the same study; however, there is evidence to suggest that vitamin D supplementation in children with the lowest levels of 25(OH)D might improve BMD. High-quality randomised trials are now required to confirm this benefit.

The FRAX(tr) algorithm uses clinical risk factors (CRF) and bone mineral density (BMD) to predict fracture risk but does not include falls history in the calculation. Using results from the Hertfordshire Cohort Study, we examined the relative contributions of CRFs, BMD and falls history to fracture prediction. We studied 2299 participants at a baseline clinic that included completion of a health questionnaire and anthropometric data. A mean of 5.5years later (range 2.9-8.8years) subjects completed a postal questionnaire detailing fall and fracture history. In a subset of 368 men and 407 women, bone densitometry was performed using a Hologic QDR 4500 instrument. There was a significantly increased risk of fracture in men and women with a previous fracture. A one standard deviation drop in femoral neck BMD was associated with a hazards ratio (HR) of incident fracture (adjusted for CRFs) of 1.92 (1.04-3.54) and 1.77 (1.16-2.71) in men and women respectively. A history of any fall since the age of 45years resulted in an unadjusted HR of fracture of 7.31 (3.78-14.14) and 8.56 (4.85-15.13) in men and women respectively. In a ROC curve analysis, the predictive capacity progressively increased as BMD and previous falls were added into an initial model using CRFs alone. Falls history is a further independent risk factor for fracture. Falls risk should be taken into consideration when assessing whether or not to commence medication for osteoporosis and should also alert the physician to the opportunity to target falls risk directly., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Context: Vitamin D deficiency during pregnancy may be associated with suboptimal fetal growth, but direct evidence is lacking., Objectives: The aim of the study was to validate a method for fetal femur volume (FV) measurement using three-dimensional ultrasound and to detect correlations between FV and maternal vitamin D concentration., Design, Setting, and Participants: A novel method for assessing FV consists of three ultrasound measurements-femur length, proximal metaphyseal diameter (PMD), and midshaft diameter-and a volume equation; this was validated by comparing ultrasound to computed tomography measurements in six pregnancies after mid-trimester termination. This method was then applied in a cohort of healthy pregnant women participating in the Southampton Women Survey. Fetal three-dimensional ultrasound and maternal 25-hydroxyvitamin D [25(OH)D] levels were performed at 34 wk; dual-energy x-ray absorptiometry of the newborn was performed shortly after birth. Univariate and multiple linear regression analyses were performed between maternal characteristics and fetal outcomes., Main Outcome Measures: We performed ultrasound measurements of the fetal femur., Results: In 357 pregnant participants, serum 25(OH)D correlated significantly with FV (P = 0.006; r = 0.147) and PMD (P = 0.001; r = 0.176); FV also demonstrated positive univariate correlations with maternal height (P < 0.001; r = 0.246), weight (P = 0.003; r = 0.160), triceps skinfold thickness (P = 0.013; r = 0.134), and a borderline negative effect from smoking (P = 0.061). On multiple regression, independent predictors of FV were the maternal height and triceps skinfold thickness; the effect of 25(OH)D on FV was attenuated, but it remained significant for PMD., Conclusion: Using a novel method for assessing FV, independent predictors of femoral size were maternal height, adiposity, and serum vitamin D. Future trials should establish whether pregnancy supplementation with vitamin D is beneficial for the fetal skeleton, using FV and PMD as fetal outcome measures.

Unlabelled: In this large, population-based, prospective, mother-offspring cohort study, maternal long chain polyunsaturated fatty acid (LCPUFA) status during pregnancy was found to be positively associated with bone mass in the offspring at age 4 years. The findings suggest that variation in intrauterine exposure to n-3 and n-6 LCPUFAs may have potential consequences for skeletal development., Introduction: Maternal diet in pregnancy has been linked to childhood bone mass, but the mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship between maternal fatty acid status and bone mass in the offspring remains unknown., Methods: We evaluated the association between maternal LCPUFA status in late pregnancy (34 weeks gestation) and bone density in their children at age 4 years within 727 mother-child pairs taking part in the Southampton Women's Survey., Results: Concentrations of the n-3 LCPUFA component of maternal plasma phosphatidylcholine were positively associated with a number of bone mineral measures at the age of 4 years; these associations persisted after adjustment for maternal body build, walking speed and infant feeding. Relationships were most evident for eicosapentaenoic acid (r = 0.09, p = 0.02 for whole body areal bone mineral density [aBMD] and r = 0.1, p = 0.008 for lumbar spine aBMD) and for docosapentaenoic acid (r = 0.09, p = 0.02 for whole body aBMD and r = 0.12, p = 0.002 for lumbar spine aBMD)., Conclusions: These findings suggest that variation in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone development and that the effects appear to persist into early childhood.

Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired. We recruited 530 children at 6 years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany). Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=-14.6 mg/mm(3) per sd, p=0.003; β=-7.7 mg/mm(3) per sd, p=0.02 respectively). These results suggest that fat mass is negatively associated with volumetric bone density at 6 years old, independent of lean mass, despite positive associations with bone size., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unlabelled: In a free-living cohort of 4-year old children, mean daily time in moderate-vigorous physical activity and daily calcium intake at 3 years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966 mg/day)., Introduction: We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density., Methods: Children aged 4 years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days., Results: Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R(2) = 3%, p < 0.001), BMC (R(2) = 4%, p < 0.001), aBMD (R (2) = 3%, p = 0.001) and estimated vBMD (R(2) = 2%, p = 0.01), but not height (r (s) = 0.04, p = 0.42) or weight (r(s) = 0.01, p = 0.76). Mean daily calcium intake (assessed at 3 years old) positively predicted bone indices in those with a calcium intake below the median (966 mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (p = 0.1) and above median was 6% (p = 0.001)., Conclusions: These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.

Alterations in expression of the imprinted gene PHLDA2 are linked to low birth weight in both humans and the mouse. However birth weight is a summary measure of fetal growth and provides little information on the growth rate of the fetus in early and late pregnancy. To examine the relation of PHLDA2 expression with rates of fetal growth and explore associations with the infant's body composition in early childhood, we measured PHLDA2 mRNA levels in the term placenta of 102 infants whose mothers were participating in the Southampton Women's Survey (SWS). Higher PHLDA2 expression was associated with a lower fetal femur growth velocity between 19 and 34 weeks gestation. In addition, higher placental PHLDA2 gene expression was associated with a lower child's bone mineral content at four years of age, measured using dual-energy X-ray absorptiometry. The results suggest that placental PHLDA2 may provide a biomarker for suboptimal skeletal growth in pregnancies uncomplicated by overt fetal growth restriction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Summary: This systematic review and meta-analysis assessed the strength and magnitude of the association between birthweight and adult bone mass. Higher birthweight was associated with higher bone mineral content of the spine and hip in adult men and women at ages between 18 and 80 years across a range of settings., Introduction: The aim of this review was to assess the strength and magnitude of the association between early size and adult bone mass., Methods: Systematic review and meta-analysis of studies that assessed the association between birthweight or weight at 1 year, and bone mineral content (BMC) or bone mineral density (BMD) in adulthood., Results: Fourteen studies met inclusion criteria. Nine assessed the relationship between birthweight and lumbar spine BMC, most showing that higher birthweight was associated with greater adult BMC. Meta-analysis demonstrated that a 1 kg increase in birthweight was associated with a 1.49 g increase in lumbar spine BMC (95% CI 0.77-2.21). Birthweight was not associated with lumbar spine BMD in 11 studies. In six studies, considering the relationship between birthweight and hip BMC, most found that higher birthweight was associated with greater BMC. Meta-analysis demonstrated that a 1 kg increase in birthweight was associated with a 1.41 g increase in hip BMC (95% CI 0.91-1.91). Seven studies considered the relationship between birthweight and hip BMD and, in most, birthweight was not a significant predictor of hip BMD. Three studies assessing the relationship between weight at 1 year and adult bone mass all reported that higher weight at one was associated with greater BMC of the lumbar spine and hip., Conclusions: Higher birthweight is associated with greater BMC of the lumbar spine and hip in adulthood. The consistency of these associations, across a range of settings, provides compelling evidence for the intrauterine programming of skeletal development and tracking of skeletal size from infancy to adulthood.

Background: We have previously demonstrated that maternal body build and lifestyle factors predict neonatal bone mineral accrual. However, the paternal determinants of neonatal bone mass are not known. In this study we explored the relationship between a father's bone mass and that of his offspring., Methods: A total of 278 pregnancies (142 male and 136 female neonates) were recruited from the Southampton Women's Survey, a unique, well-established cohort of women, aged 20-34 yr, who had been assessed before and during pregnancy. The neonates and their fathers underwent whole body dual-x-ray absorptiometry (DXA) within 2 wk of birth using a Lunar DPX (General Electric Corp., Madison, WI) and Hologic Discovery instrument (Hologic Inc., Bedford, MA), respectively; correlation and regression methods were used to explore the parental determinants of neonatal bone mass., Results: After adjusting the paternal DXA indices for father's age and the neonatal for baby's gestational age and age at DXA scan, there were highly significant positive associations between baby's whole body bone area, bone mineral content, and bone mineral density and the corresponding indices in the father (P = 0.003, 0.0002, 0.046, respectively) among female infants. These relationships were independent of maternal height and fat stores. The associations for male infants with paternal DXA indices did not achieve statistical significance., Conclusions: The father's skeletal size predicts skeletal size more strongly in female than male offspring, independently of the mother's body build. These data point toward the importance of considering paternal genotype in studies exploring the developmental origins of osteoporotic fracture and raise intriguing mechanistic questions about the gender specificity of influences on intrauterine bone mineral accrual.

Evidence is accruing that environmental exposures during critical periods of early development induce persisting changes in skeletal growth, and alter fracture risk in later life. We have previously demonstrated that placental calcium transport, partly determined by maternal 25-(OH) vitamin D status, may underlie this phenomenon. However, the precise relationship between expression of calcium transport proteins in the human placenta, and neonatal bone mineral accrual in the offspring, remains unknown. Tissue samples from 70 human placentae were fast frozen in liquid nitrogen and stored at -70 degrees C. A quantitative real time reverse transcriptase polymerase chain reaction was used to measure the mRNA expression of PMCA isoforms 1-4, using beta-actin as a control gene. Neonatal whole body bone area, mineral content and areal density (BA, BMC, BMD) were measured within 2 weeks of birth using DXA. PMCA3 mRNA expression predicted BA (r=0.28, p=0.02), BMC (r=0.25, p=0.04), placental weight (r=0.26, p=0.04) and birth weight (r=0.33, p=0.006) of the neonate. In a multivariate model, the relationship between placental PMCA3 expression and neonatal BMC was independent of maternal height, pre-pregnant fat stores, parity, physical activity, smoking, and calcium intake (p<0.05). Expression of the placental calcium transporter PMCA3 mRNA predicts neonatal whole body bone mineral content. This association may explain, in part, the mechanism whereby a mother's 25(OH)-vitamin D stores influence her offspring's bone mass.

Background: Vitamin D insufficiency is common in women of childbearing age and increasing evidence suggests that the risk of osteoporotic fracture in adulthood could be determined partly by environmental factors during intrauterine and early postnatal life. We investigated the effect of maternal vitamin D status during pregnancy on childhood skeletal growth., Methods: In a longitudinal study, we studied 198 children born in 1991-92 in a hospital in Southampton, UK; the body build, nutrition, and vitamin D status of their mothers had been characterised during pregnancy. The children were followed up at age 9 years to relate these maternal characteristics to their body size and bone mass., Findings: 49 (31%) mothers had insufficient and 28 (18%) had deficient circulating concentrations of 25(OH)-vitamin D during late pregnancy. Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body (r=0.21, p=0.0088) and lumbar-spine (r=0.17, p=0.03) bone-mineral content in children at age 9 years. Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p<0.0001 and p=0.0110, respectively) and childhood bone mass (p=0.0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p=0.0286)., Interpretation: Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium. Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.

UnlabelledThe Committee of Scientific Advisors of International Osteoporosis Foundation (IOF) recommends that papers describing the descriptive epidemiology of osteoporosis using bone mineral density (BMD) at the femoral neck include T-scores derived from an international reference standard.IntroductionThe prevalence of osteoporosis as defined by the T-score is inconsistently reported in the literature which makes comparisons between studies problematic.MethodsThe Epidemiology and Quality of Life Working Group of IOF convened to make its recommendations and endorsement sought thereafter from the Committee of Scientific Advisors of IOF.ResultsThe Committee of Scientific Advisors of IOF recommends that papers describing the descriptive epidemiology of osteoporosis using BMD at the femoral neck include T-scores derived from the National Health and Nutrition Examination Survey III reference database for femoral neck measurements in Caucasian women aged 20-29 years.ConclusionsIt is expected that the use of the reference standard will help resolve difficulties in the comparison of results between studies and the comparative assessment of new technologies.

Summary: Vertebral fracture (VF) is a strong predictor of subsequent fracture. In this study of older women, VF, identified by dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA), were associated with an increased risk of incident fractures and had a substantial impact on fracture probability, supporting the utility of VFA in clinical practice. Purpose: Clinical and occult VF can be identified using VFA with dual-energy X-ray absorptiometry (DXA). The aim of this study was to investigate to what extent VFA-identified VF improve fracture risk prediction, independently of bone mineral density (BMD) and clinical risk factors used in FRAX. Methods: A total of 2852 women, 75–80 years old, from the prospective population-based study SUPERB cohort, were included in this study. At baseline, BMD was measured by DXA, VF diagnosed by VFA, and questionnaires used to collect data on risk factors for fractures. Incident fractures were captured by X-ray records or by diagnosis codes. An extension of Poisson regression was used to estimate the association between VFA-identified VF and the risk of fracture and the 5- and 10-year probability of major osteoporotic fracture (MOF) was calculated from the hazard functions for fracture and death. Results: During a median follow-up of 5.15 years (IQR 4.3–5.9 years), the number of women who died or suffered a MOF, clinical VF, or hip fracture was 229, 422, 160, and 124, respectively. A VFA-identified VF was associated with an increased risk of incident MOF (hazard ratio [HR] = 1.78; 95% confidence interval [CI] 1.46–2.18), clinical VF (HR = 2.88; 95% [CI] 2.11–3.93), and hip fracture (HR = 1.67; 95% [CI] 1.15–2.42), adjusted for age, height, and weight. For women at age 75 years, a VFA-identified VF was associated with 1.2–1.4-fold greater 10-year MOF probability compared with not taking VFA into account, depending on BMD. Conclusion: Identifying an occult VF using VFA has a substantial impact on fracture probability, indicating that VFA is an efficient method to improve fracture prediction in older women. [ABSTRACT FROM AUTHOR]

Blood pressure and bone metabolism appear to share commonalities in their physiologic regulation. Specific antihypertensive drug classes may also influence bone mineral density. However, current evidence from existing observational studies and randomised trials is insufficient to establish causal associations for blood pressure and use of blood pressure–lowering drugs with bone health outcomes, particularly with the risks of osteoporosis and fractures. The availability and access to relevant large-scale biomedical data sources as well as developments in study designs and analytical approaches provide opportunities to examine the nature of the association between blood pressure and bone health more reliably and in greater detail than has ever been possible. It is unlikely that a single source of data or study design can provide a definitive answer. However, with appropriate considerations of the strengths and limitations of the different data sources and analytical techniques, we should be able to advance our understanding of the role of raised blood pressure and its drug treatment on the risks of low bone mineral density and fractures. As elevated blood pressure is highly prevalent and blood pressure–lowering drugs are widely prescribed, even small effects of these exposures on bone health outcomes could be important at a population level. [ABSTRACT FROM AUTHOR]

The introduction of the FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well-validated risk factors for fracture with or without the use of bone mineral density. Since age-specific rates of fracture and death differ across the world, FRAX models are calibrated with regard to the epidemiology of hip fracture (preferably from national sources) and mortality (usually United Nations sources). Models are currently available for 73 nations or territories covering more than 80% of the world population. FRAX has been incorporated into more than 80 guidelines worldwide, although the nature of this application has been heterogeneous. The limitations of FRAX have been extensively reviewed. Arithmetic procedures have been proposed in order to address some of these limitations, which can be applied to conventional FRAX estimates to accommodate knowledge of dose exposure to glucocorticoids, concurrent data on lumbar spine bone mineral density, information on trabecular bone score, hip axis length, falls history, type 2 diabetes, immigration status and recency of prior fracture. [ABSTRACT FROM AUTHOR]

Osteoporosis is a disease characterized by impaired bone microarchitecture and reduced bone mineral density (BMD) resulting in bone fragility and increased risk of fracture. In western societies, one in three women and one in five men will sustain an osteoporotic fracture in their remaining lifetime from the age of 50 years. Fragility fractures, especially of the spine and hip, commonly give rise to increased morbidity and mortality. In the five largest European countries and Sweden, fragility fractures were the cause of 2.6 million disability-adjusted life years in 2016 and the fracture-related costs increased from €29.6 billion in 2010 to €37.5 billion in 2017. In the European Union and the USA, only a small proportion of women eligible for pharmacological treatment are being prescribed osteoporosis medication. Secondary fracture prevention, using Fracture Liaison Services, can be used to increase the rates of fracture risk assessment, BMD testing and use of osteoporosis medication in order to reduce fracture numbers. Additionally, established primary prevention strategies, based on case-finding methods utilizing fracture prediction tools, such as FRAX, to identify women without fracture but with elevated risk, are recommended in order to further reduce fracture numbers. [ABSTRACT FROM AUTHOR]

Summary: In women of ages 75–80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction: Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods: The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75–80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results: During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49–6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34–1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26–2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). Conclusion: A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women. [ABSTRACT FROM AUTHOR]

Summary: In a simulated population of older women, we demonstrate that an upward shift in the population distribution of BMD by approximately 0.3SD may decrease the risk of incident fractures to the same extent as an intervention targeted to those with T-score less than −2.5. Introduction: To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. Methods: We used a simulated cohort of 49,242 women with age and body mass index distribution from the UK, and prevalence of other clinical risk factors based on European FRAX® cohorts. Using FRAX probabilities of major osteoporotic fracture (MOF: hip, clinical vertebral, distal forearm, proximal humerus) and hip fracture, calculated with femoral neck BMD, we determined the expected number of fractures over 10 years, stratified by 10-year age band from 50 years. We then investigated the effect of (i) uplifting all individuals with T-score below −2.5 to be exactly −2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). Results: Overall, the high-risk strategy prevented 573 MOF including 465 hip fractures. Moving the BMD T-score distribution upward by 0.27SD gave an equivalent reduction in numbers of MOF; for hip fractures prevented, this was 0.35SD. A global upward 0.25SD BMD shift prevented 524 MOF including 354 hip fractures, with corresponding figures for an increase of 0.5SD being 973 MOF prevented and 640 hip fractures prevented. The ratio of hip fracture to MOF prevented differed by the two approaches, such that for the high-risk strategy, the ratio was 0.81, and for the population strategy was 0.68 (0.25SD BMD uplift) and 0.66 (0.5SD BMD uplift). The numbers of fractures prevented by the high-risk strategy increased with age. In contrast, the age-related increase in numbers of fractures prevented with the population strategy rose with age, but peaked in the 70–79-year age band and declined thereafter. Conclusions: Both strategies reduced the numbers of expected incident fractures, with contrasting relative impacts by age and fracture site. Whilst the current analysis used UK/European anthropometric/risk factor distributions, further analyses calibrated to the distributions in other settings globally may be readily undertaken. Overall, these findings support the investigation of both population level interventions and those targeted at high fracture risk groups. [ABSTRACT FROM AUTHOR]

Summary: The effects of COVID-19 have the potential to impact on the management of chronic diseases including osteoporosis. A global survey has demonstrated that these impacts include an increase in telemedicine consultations, delays in DXA scanning, interruptions in the supply of medications and reductions in parenteral medication delivery. Introduction: The COVID-19 pandemic has had profound effects on the health of the global population both directly, via the sequelae of the infection, and indirectly, including the relative neglect of chronic disease management. Together the International Osteoporosis Foundation and National Osteoporosis Foundation sought to ascertain the impact on osteoporosis management. Methods: Questionnaires were electronically circulated to a sample of members of both learned bodies and included information regarding the location and specialty of respondents, current extent of face to face consultations, alterations in osteoporosis risk assessment, telemedicine experience, alterations to medication ascertainment and delivery and electronic health record (EHR) utilisation. Responses were collected, quantitative data analysed, and qualitative data assessed for recurring themes. Results: Responses were received from 209 healthcare workers from 53 countries, including 28% from Europe, 24% from North America, 19% from the Asia Pacific region, 17% from the Middle East and 12% from Latin America. Most respondents were physicians (85%) with physician assistants, physical therapists and nurses/nurse practitioners represented in the sample. The main three specialties represented included rheumatology (40%), endocrinology (22%) and orthopaedics (15%). In terms of the type of patient contact, 33% of respondents conducted telephone consultations and 21% video consultations. Bone mineral density assessment by dual-energy X-ray absorptiometry (DXA) usage was affected with only 29% able to obtain a scan as recommended. The majority of clinicians (60%) had systems in place to identify patients receiving parenteral medication, and 43% of clinicians reported difficulty in arranging appropriate osteoporosis medications during the COVID-19 crisis. Conclusions: To conclude through surveying a global sample of osteoporosis healthcare professionals, we have observed an increase in telemedicine consultations, delays in DXA scanning, interrupted supply of medications and reductions in parenteral medication delivery. [ABSTRACT FROM AUTHOR]

Summary: Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. Summary points: • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events. [ABSTRACT FROM AUTHOR]

Summary: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. Introduction: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. Methods: A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75–80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. Results: Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80–3.18] and hip fracture 2.96 [1.62–5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5–1.9 in a 75-year-old woman with slow TUG (> 12 s). Conclusion: The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women. [ABSTRACT FROM AUTHOR]

Summary: Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma. Introduction: Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Methods: Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. Results: The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8 years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08–1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47–1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. Conclusions: High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk. [ABSTRACT FROM AUTHOR]

Summary: Lumbar spine trabecular bone score (TBS) can be used to modify the output from the fracture risk assessment tool, FRAX, to enhance fracture prediction. An alternative approach for using TBS in clinical practice, based upon an adjustment to the bone mineral density (BMD) T-score, may be helpful in regions where intervention guidelines and/or reimbursement are primarily based on BMD T-score.Introduction: The aim of this study is to develop an approach for using TBS in clinical practice based upon a “risk-equivalent” adjustment to the BMD T-score.Methods: We identified 45,185 women age 40 years and older with baseline spine and hip DXA, TBS, and FRAX probabilities including femoral neck BMD. Incident major osteoporotic fractures (MOF, n = 3925) were identified from population-based health services data (mean follow-up 7.4 years comprising 335,910 person-years). Cox proportional hazards models adjusted for age and BMI were first used to estimate the risk for MOF from BMD T-score alone, then after including TBS and a multiplicative age interaction term. From the parameter estimates, we developed a TBS offset to the BMD T-score based upon change in TBS that would give the same risk as a unit change in BMD T-score for the femoral neck, total hip, and lumbar spine.Results: All BMD measurements, TBS, and the age interaction term independently predicted MOF (p < 0.001). Measures of risk stratification and model fit were improved for the TBS-adjusted BMD T-score versus the unadjusted BMD T-score (p < 0.001). There was a high level of agreement between MOF probability estimated from TBS-adjusted MOF FRAX probability and FRAX probability using the “risk-equivalent” femoral BMD T-score: MOF probability r2 = 0.98, slope = 1.02, intercept = − 0.3; hip probability r2 = 0.95, slope = 1.07, intercept = 0.0.Conclusions: The BMD-independent effect of lumbar spine TBS on fracture risk can be estimated as a simple offset to the BMD T-score. [ABSTRACT FROM AUTHOR]

A correction to the article "Elevated blood pressure, antihypertensive medications and bone health in the population: revisiting old hypotheses and exploring future research directions" is presented which appeared in the previous issue of the periodical.

Summary: Falls and fractures share several common risk factors. Although past falls is not included as an input variable in the FRAX calculator, we demonstrate that FRAX probability predicts risk of incident falls in the MrOs Sweden cohort. Introduction: Although not included in the FRAX® algorithm, it is possible that increased falls risk is partly dependent on other risk factors that are incorporated into FRAX. The aim of the present study was to determine whether fracture probability generated by FRAX might also predict risk of incident falls and the extent that a falls history would add value to FRAX. Methods: We studied the relationship between FRAX probabilities and risk of falls in 1836 elderly men recruited to the MrOS study, a population-based prospective cohort of men from Sweden. Baseline data included falls history, clinical risk factors, bone mineral density (BMD) at femoral neck, and calculated FRAX probabilities. Incident falls were captured during an average of 1.8 years of follow-up. An extension of Poisson regression was used to investigate the relationship between FRAX, other risk variables, and the time-to-event hazard function of falls. All associations were adjusted for age and time since baseline. Results: At enrolment, 15.5 % of the men had fallen during the preceding 12 months (past falls) and 39 % experienced one or more falls during follow-up (incident falls). The risk of incident falls increased with increasing FRAX probabilities at baseline (hazard ratio (HR) per standard deviation (SD), 1.16; 95 % confidence interval (95%CI), 1.06 to 1.26). The association between incident falls and FRAX probability remained after adjustment for past falls (HR per SD, 1.12; 95%CI, 1.03 to 1.22). High compared with low baseline FRAX score (>15 vs <15 % probability of major osteoporotic fracture) was strongly predictive of increased falls risk (HR, 1.64; 95%CI, 1.36 to 1.97) and remained stable with time. Whereas past falls were a significant predictor of incident falls (HR, 2.75; 95%CI, 2.32 to 3.25), even after adjustment for FRAX, the hazard ratio decreased markedly with increasing follow-up time. Conclusions: Although falls are not included as an input variable, FRAX captures a component of risk for future falls and outperforms falls history with an extended follow-up time. [ABSTRACT FROM AUTHOR]

The major application of FRAX in osteoporosis is to direct pharmacological interventions to those at high risk of fracture. Whereas the efficacy of osteoporosis treatment, with the possible exception of alendronate, is largely independent of baseline bone mineral density (BMD), it remains a widely held perception that osteoporosis therapies are only effective in the presence of low BMD. Thus, the use of FRAX in the absence of BMD to identify individuals requiring therapy remains the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high evidence-based validity to identify a risk responsive to intervention. The selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD and thus identifies a risk that is responsive to pharmacological intervention. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where facilities for BMD testing are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Thus concerns surrounding the use of FRAX in clinical practice without information on BMD are largely misplaced. [ABSTRACT FROM PUBLISHER]

Summary: Under current guidelines, based on prior fracture probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold (a fixed threshold from the age of 70 years) reduces this disparity, increases treatment access and decreases the need for bone densitometry. Introduction: Several international guidelines set age-specific intervention thresholds at the 10-year probability of fracture equivalent to a woman of average BMI with a prior fracture. At older ages (≥70 years), women with prior fracture selected for treatment are at lower average absolute risk than those selected for treatment in the absence of prior fracture, prompting consideration of alternative thresholds in this age group. Methods: Using a simulated population of 50,633 women aged 50-90 years in the UK, with a distribution of risk factors similar to that in the European FRAX derivation cohorts and a UK-matched age distribution, the current NOGG intervention and assessment thresholds were compared to one where the thresholds remained constant from 70 years upwards. Results: Under current thresholds, 45.1 % of women aged ≥70 years would be eligible for therapy, comprising 37.5 % with prior fracture, 2.2 % with high risk but no prior fracture and 5.4 % selected for treatment after bone mineral density (BMD) measurement. Mean hip fracture probability was 11.3, 23.3 and 17.6 %, respectively, in these groups. Under the alternative thresholds, the overall proportion of women treated increased from 45.1 to 52.9 %, with 8.4 % at high risk but no prior fracture and 7.0 % selected for treatment after BMD measurement. In the latter group, the mean probability of hip fracture was identical to that observed in women with prior fracture (11.3 %). The alternative threshold also reduced the need for BMD measurement, particularly at older ages (>80 years). Conclusions: The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages. [ABSTRACT FROM AUTHOR]

Summary: The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time. Introduction: The aim of this meta-analysis was to investigate the association between parameters of QUS and risk of fracture. Methods: In an individual-level analysis, we studied participants in nine prospective cohorts from Asia, Europe and North America. Heel broadband ultrasonic attenuation (BUA dB/MHz) and speed of sound (SOS m/s) were measured at baseline. Fractures during follow-up were collected by self-report and in some cohorts confirmed by radiography. An extension of Poisson regression was used to examine the gradient of risk (GR, hazard ratio per 1 SD decrease) between QUS and fracture risk adjusted for age and time since baseline in each cohort. Interactions between QUS and age and time since baseline were explored. Results: Baseline measurements were available in 46,124 men and women, mean age 70 years (range 20-100). Three thousand and eighteen osteoporotic fractures (787 hip fractures) occurred during follow-up of 214,000 person-years. The summary GR for osteoporotic fracture was similar for both BUA (1.45, 95 % confidence intervals (CI) 1.40-1.51) and SOS (1.42, 95 % CI 1.36-1.47). For hip fracture, the respective GRs were 1.69 (95 % CI, 1.56-1.82) and 1.60 (95 % CI, 1.48-1.72). However, the GR was significantly higher for both fracture outcomes at lower baseline BUA and SOS ( p < 0.001). The predictive value of QUS was the same for men and women and for all ages ( p > 0.20), but the predictive value of both BUA and SOS for osteoporotic fracture decreased with time ( p = 0.018 and p = 0.010, respectively). For example, the GR of BUA for osteoporotic fracture, adjusted for age, was 1.51 (95 % CI 1.42-1.61) at 1 year after baseline, but at 5 years, it was 1.36 (95 % CI 1.27-1.46). Conclusions: Our results confirm that quantitative ultrasound is an independent predictor of fracture for men and women particularly at low QUS values. [ABSTRACT FROM AUTHOR]

Osteoporosis is a major public health problem due to consequent fragility fractures; data from the UK suggest that up to 50% of women and 20% men aged 50 years will have an osteoporosis-related fracture in their remaining lifetime. Skeletal size and density increase from early embryogenesis through intrauterine, infant, childhood and adult life to reach a peak in the third to fourth decade. The peak bone mass achieved is a strong predictor of later osteoporosis risk. Epidemiological studies have demonstrated a positive relationship between early growth and later bone mass, both at peak and in later life, and also with reduced risk of hip fracture. Mother-offspring cohorts have allowed the elucidation of some of the specific factors in early life, such as maternal body build, lifestyle and 25(OH)-vitamin D status, which might be important. Most recently, the phenomenon of developmental plasticity, whereby a single genotype may give rise to different phenotypes depending on the prevailing environment, and the science of epigenetics have presented novel molecular mechanisms which may underlie previous observations. This review will give an overview of these latter developments in the context of the burden of osteoporosis and the wider data supporting the link between the early environment and bone health in later life. [ABSTRACT FROM AUTHOR]