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Osteoarthritis (OA) is the commonest joint condition globally, affecting 18 % of women over the age of 60 years, although the prevalence varies according to the definition used. Although it may develop in any joint, it most commonly affects joints of the knee, hip, hand, spine and foot. Because OA often emerges in women in midlife, there has been longstanding interest in the association between hormonal status and the development and progression of OA. Researchers have variably suggested that estrogen exposure may be a risk factor for OA development, or that, conversely, it may be used as a therapy to treat OA. This review considers the historical development of this question, first described in the literature in 1805, and highlights the need for future research in this area. [ABSTRACT FROM AUTHOR]

Objectives To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), an area of high unmet clinical need. Methods The European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) organized a working group under the auspices of the International Osteoporosis Foundation (IOF) and the World Health Organization (WHO). Results This consensus guideline is intended to provide a reference tool for practice, and should allow for better standardization of the conduct of clinical trials in hand OA. Hand OA is a heterogeneous disease affecting different, and often multiple, joints of the thumb and fingers. It was recognized that the various phenotypes and limitations of diagnostic criteria may make the results of hand OA trials difficult to interpret. Nonetheless, practical recommendations for the conduct of clinical trials of both symptom and structure modifying drugs are outlined in this consensus statement, including guidance on study design, execution, and analysis. Conclusions While the working group acknowledges that the methodology for performing clinical trials in hand OA will evolve as knowledge of the disease increases, it is hoped that this guidance will support the development of new pharmacological treatments targeting hand OA. [ABSTRACT FROM AUTHOR]

Pain is a key symptom of osteoarthritis (OA) and has been linked to poor mental health. Pain fluctuates over time within individuals, but a paucity of studies have considered day-to-day fluctuations of joint pain in relation to affective symptoms in older persons with OA. This study investigated the relationship of pain severity as well as within-person pain variability with anxiety and depression symptoms in 832 older adults with OA who participated in the European Project on OSteoArthritis (EPOSA): a 6-country cohort study. Affective symptoms were examined with the Hospital Anxiety and Depression Scale, pain severity was assessed with the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand Osteoarthritis Index, and intraindividual pain variability was measured using pain calendars assessed at baseline, 6, and 12 to 18 months. Age-stratified multiple linear regression analyses adjusted for relevant confounders showed that more pain was associated with more affective symptoms in older-old participants (74.1–85 years). Moreover, older-old participants experienced fewer symptoms of anxiety (ratio = .85, 95% confidence interval [CI], .77–.94), depression (ratio = .90, 95% CI, .82–.98), and total affective symptoms (ratio = .87, 95% CI, .79–.94) if their pain fluctuated more. No such association was evident in younger-old participants (65–74.0 years). These findings imply that stable pain levels are more detrimental to mental health than fluctuating pain levels in older persons. Perspective This study showed that more severe and stable joint pain levels were associated with anxiety and depressive symptoms in older persons with OA. These findings emphasize the importance of measuring pain in OA at multiple time points, because joint pain fluctuations may be an indicator for the presence of affective symptoms. [ABSTRACT FROM AUTHOR]

Background: Studies in older adults and animals have suggested contrasting relations between bone health and different vitamin A compounds. To our knowledge, the associations between maternal vitamin A status and offspring bone development have not previously been elucidated. Objective: We examined the associations between maternal serum retinol and β-carotene concentrations during late pregnancy and offspring bone mineralization assessed at birth with the use of dual-energy X-ray absorptiometry. Design: In the Southampton Women’s Survey mother-offspring birth cohort, maternal health, lifestyle, and diet were assessed prepregnancy and at 11 and 34 wk of gestation. In late pregnancy, maternal serum retinol and β-carotene concentrations were measured. Offspring total body bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were measured within 2 wk after birth. Results: In total, 520 and 446 mother-offspring pairs had measurements of maternal serum retinol and β-carotene, respectively. Higher maternal serum retinol in late pregnancy was associated with lower offspring total body BMC (β = −0.10 SD/SD; 95% CI: −0.19, −0.02; P = 0.020) and BA (β = −0.12 SD/SD; 95% CI: −0.20, −0.03; P = 0.009) but not BMD. Conversely, higher maternal serum β-carotene concentrations in late pregnancy were associated with greater total body BMC (β = 0.12 SD/SD; 95% CI: 0.02, 0.21; P = 0.016) and BA (β = 0.12 SD/SD; 95% CI: 0.03, 0.22; P = 0.010) but not BMD. Conclusions: Maternal serum retinol and β-carotene concentrations had differing associations with offspring bone size and growth at birth: retinol was negatively associated with these measurements, whereas β-carotene was positively associated. These findings highlight the need for further investigation of the effects of maternal retinol and carotenoid status on offspring bone development. [ABSTRACT FROM AUTHOR]

Background: The role of maternal 25-hydroxyvitamin D [25(OH)D] in fetal development is uncertain, and findings of observational studies have been inconsistent. Most studies have assessed 25(OH)D only one time during pregnancy, but to our knowledge, the tracking of an individual's 25(OH)D during pregnancy has not been assessed previously. Objective: We determined the tracking of serum 25(OH)D from early to late pregnancy and factors that influence this. Design: The Southampton Women's Survey is a prospective mother-offspring birth-cohort study. Lifestyle, diet, and 25(OH)D status were assessed at 11 and 34 wk of gestation. A Fourier transformation was used to model the seasonal variation in 25(OH)D for early and late pregnancy separately, and the difference between the measured and seasonally modeled 25(OH)D was calculated to generate a season-corrected 25(OH)D. Tracking was assessed with the use of the Pearson correlation coefficient, and multivariate linear regression was used to determine factors associated with the change in season-corrected 25(OH)D. Results: A total of 1753 women had 25(OH)D measured in both early and late pregnancy. There was a moderate correlation between season-corrected 25(OH)D measurements at 11 and 34 wk of gestation (r = 0.53, P, 0.0001; n = 1753). Vitamin D supplementation was the strongest predictor of tracking; in comparison with women who never used supplements, the discontinuation of supplementation after 11 wk was associated with a reduction in season-corrected 25(OH)D (β = 27.3 nmol/L; P, 0.001), whereas the commencement (β = 12.6 nmol/L; P, 0.001) or continuation (β = 6.6 nmol/L; P, 0.001) of supplementation was associated with increases in season-corrected 25(OH)D. Higher pregnancy weight gain was associated with a reduction in season-corrected 25(OH)D (β = 20.4 nmol µ L-1 µ kg-1; P = 0.015), whereas greater physical activity (β = 0.4 nmol/L per h/wk; P = 0.011) was associated with increases. Conclusions: There is a moderate tracking of 25(OH)D status through pregnancy; factors such as vitamin D supplementation, weight gain, and physical activity are associated with changes in season-corrected 25(OH)D from early to late gestation. These findings have implications for study designs and analyses and approaches to intervention studies and clinical care. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Greater awareness of the relationship between co-morbidities and fracture risk may improve fracture-prediction algorithms such as FRAX. Materials and methods: We used a large, multinational cohort study (GLOW) to investigate the effect of co-morbidities on fracture risk. Women completed a baseline questionnaire detailing past medical history, including co-morbidity history and fracture. They were re-contacted annually to determine incident clinical fractures. A co-morbidity index, defined as number of baseline co-morbidities, was derived. The effect of adding the co-morbidity index to FRAX risk factors on fracture prevention was examined using chi-squared tests, the May–Hosmer test, c index and comparison of predicted versus observed fracture rates. Results: Of 52,960 women with follow-up data, enrolled between October 2006 and February 2008, 3224 (6.1%) sustained an incident fracture over 2years. All recorded co-morbidities were significantly associated with fracture, except for high cholesterol, hypertension, celiac disease, and cancer. The strongest association was seen with Parkinson''s disease (age-adjusted hazard ratio [HR]: 2.2; 95% CI: 1.6–3.1; P <0.001). Co-morbidities that contributed most to fracture prediction in a Cox regression model with FRAX risk factors as additional predictors were: Parkinson''s disease, multiple sclerosis, chronic obstructive pulmonary disease, osteoarthritis, and heart disease. Conclusion: Co-morbidities, as captured in a co-morbidity index, contributed significantly to fracture risk in this study population. Parkinson''s disease carried a particularly high risk of fracture; and increasing co-morbidity index was associated with increasing fracture risk. Addition of co-morbidity index to FRAX risk factors improved fracture prediction. [Copyright &y& Elsevier]

Abstract: Little is known about the potential effects of neighbourhood environment on positive mental health in older people. We examined cross-sectional associations between the index of multiple deprivation score of the census area of residence, perceptions of neighbourhood cohesion and neighbourhood problems and mental wellbeing, as measured by the Warwick–Edinburgh Mental Wellbeing Scale, in 1157 men and women aged 69–78 years from Hertfordshire, UK. We found no association between area-level deprivation and mental wellbeing. People who felt a stronger sense of cohesion within their neighbourhood and reported fewer neighbourhood problems had higher levels of mental wellbeing, independently of social class, income, presence of limiting illness or disability, mobility problems, and perceived social support. Adjustment for emotional stability attenuated the associations between mental wellbeing and both of these measures of perceived neighbourhood environment, particularly in the case of neighbourhood problems. How older people feel about their neighbourhood may be important for positive mental health in later life. [Copyright &y& Elsevier]

Abstract: Little is known about the impact of concomitant vitamin D deficiency on bone mineral density in hyperthyroidism. Therefore, we evaluated bone mineral measures in vitamin D–deficient and sufficient patients with hyperthyroidism. Thirty newly diagnosed consecutive patients with hyperthyroidism were included. Blood samples were used for measurement of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D [25(OH) D], and parathyroid hormone (PTH). Bone mineral density (BMD) was measured at the hip, spine, and forearm. The patients were divided into vitamin D–deficient (<25nmol/L) and vitamin D–sufficient groups (≥25nmol/L). Eight (26.6%) patients had 25(OH) D levels less than 25nmol/L, with mean±standard deviation (SD) level of 16.5±3.2 (vitamin D–deficient group 1), and the remainder had a mean±SD of 46.0±13.5nmol/L (vitamin D–sufficient group 2). Serum-intact PTH levels were significantly higher in group 1 compared with those in group 2 (31.2±16.3 vs 18.0±13.1pg/mL; p =0.041). In the vitamin D–deficient group, the mean BMD T-scores were in the osteoporotic range at hip and forearm (−2.65±1.13 and −3.04±1.3) and in the osteopenia range at lumbar spine (−1.83±1.71). However, in vitamin D–sufficient group, the mean BMD T-scores were in the osteopenia range (−1.64±1.0, −1.27±1.6, and −1.60±0.7) at hip, forearm, and lumbar spine, respectively. The mean BMD Z-scores were also significantly lower in vitamin D–deficient group compared with those in vitamin D–sufficient group. Finally, BMD values (gm/cm2) at the hip and forearm were significantly lower in the vitamin D–deficient group compared with those in the vitamin D–sufficient group. In conclusion, hyperthyroid patients with concomitant vitamin D deficiency had lower BMD compared with vitamin D–sufficient patients. [Copyright &y& Elsevier]

Background: Blood cholesterol responses to the manipulation of dietary fat vary widely between persons. Although epidemiologic evidence suggests that prenatal growth and nutrition influence adult cholesterol homeostasis, whether prenatal growth modifies the association between dietary fat intake and serum cholesterol concentration in adults is unknown. Objective: The aim was to examine the relation between fat intake and serum cholesterol concentrations in men and women whose birth weights were known. Design: We studied a cohort of men and women aged 59-71 y. Diet was assessed with a food-frequency questionnaire. Total, HDL-, and LDL-cholesterol concentrations and the ratio of HDL to LDL cholesterol were measured in fasting blood samples from 574 men and 562 women who did not have coronary heart disease. Results: Total and saturated fat intakes were not associated with serum cholesterol concentrations in men or women. However, subdivision by birth weight showed associations in men but not in women. High intakes of total and saturated fat were associated with reduced HDL-cholesterol concentrations in men with birth weights ⩽3.2 kg (7 lb) but not in men with higher birth weights. Similar effects on the HDL-to-LDL cholesterol ratio were observed (P for interaction = 0.02 for total fat and 0.01 for saturated fat). When 32 men taking cholesterol-lowering medication were excluded, the interactions were strengthened (P = 0.008 and 0.006, respectively). Conclusion: The adverse effects of high intakes of total and saturated fat on serum cholesterol concentrations in men may be confined to those with lower birth weights. [ABSTRACT FROM AUTHOR]

Background: Size in early life is related to adult body mass index, and early environmental influences have been proposed to have lifelong consequences for obesity. However, body mass index also reflects fat-free mass, and few studies have examined the relation between size in early life and direct measures of body composition in older people. Objective: We investigated the associations of birth weight and weight at 1 y of age with body composition in older men. Design: We carried out a retrospective cohort study in Hertfordshire, United Kingdom. Men who were born between 1931 and 1939 and for whom there were records of birth weight and weight at 1 y of age (n = 737) participated in the study. The main outcome measures were adult body mass index, fat-free mass, and fat mass. Results: Birth weight was significantly and consistently positively associated with adult body mass index and fat-free mass but not with measures of adult fat mass. In contrast, weight at 1 y of age was associated with adult body mass index, fat-free mass, and fat mass. Conclusions: The consistently reported positive relation between birth weight and adult body mass index may reflect prenatal and maternal influences on fat-free mass rather than on fat mass in older people. The postnatal environment may be more influential than prenatal factors in the development of obesity in later life. [ABSTRACT FROM AUTHOR]

Abstract Purpose To evaluate the effects of different definitions of glucocorticoid (GC) exposure on the magnitude and pattern of fracture risk using the same dataset. Methods Data from patients with rheumatoid arthritis (RA) were extracted from the Clinical Practice Research Datalink, a primary care database with electronic health records in the United Kingdom. Patients exposed to oral GCs were matched to up to two unexposed patients by age, gender and location. The first osteoporotic fracture was identified and adjusted and unadjusted cox proportional hazard ratios (HR) and 95% confidence intervals (CI) produced for fracture risk following GC therapy using different models of risk attribution. These include models demonstrating the effect of dose, duration and recency of GC exposure. Results There were 16,507 patients included. Exposed patients were older and had more comorbidities. GC therapy was associated with an increased risk of fracture, with the effect size influenced by risk attribution model. The risk of fracture decreased with less recent exposure from HR (95% CI) 1.66 (1.27, 2.16) during the first month of stopping GCs to 1.11 (0.79, 1.57) for between 1 and 3 months. The risk of fracture increased with current daily dose, HR 1.44 (1.17, 1.77) for 5–9.9 mg prednisolone equivalent dose (PEQ) to 3.02 (1.77, 5.15) for 15–19.9 mg PEQ. Risk of fracture increased with cumulative dose, a function of dose and duration, from HR 1.22 (1.03, 1.44) for <1 g to 1.83 (1.35, 2.48) for 7.5–10 g. Conclusion GC exposure was associated with excess fracture risk, with effect size differing according to definition of exposure. This highlights the need to incorporate all exposure dimensions (dose, duration and recency) in these patient's fracture risk assessments. Highlights • We compared definitions of glucocorticoid exposure and their associated risk of fracture. • Dose, duration and recency of oral glucocorticoid exposure individually affect the risk of fracture. • Dose, duration and recency of glucocorticoid exposure is not yet incorporated into fracture risk calculators. • Clinicians should consider the combined effects of dose, duration and recency of exposure when assessing fracture risk. [ABSTRACT FROM AUTHOR]

Ethnic differences in bone mineral density (BMD) and fracture risk are well-described; the aim of this study was to investigate whether central adiposity or inflammatory status contribute to these ethnic differences in BMD in later life. The Southall and Brent Revisited study (SABRE) is a UK-based tri-ethnic cohort of men and women of European, South Asian or African Caribbean origin. At the most recent SABRE follow-up (2014–2018), in addition to measures of cardiometabolic phenotype, participants had dual-energy X-ray absorptiometry (DXA) bone and body composition scans. Multiple linear regression was used to determine whether markers of body composition, central adiposity or inflammatory status contributed to ethnic differences in BMD. In men and women, age- and height-adjusted BMD at all sites was higher in African Caribbeans compared to Europeans (femoral neck: standardised β (95% confidence interval): men: 1.00SD (0.75, 1.25); women: 0.77SD (0.56, 0.99)). South Asian men had higher BMD than European men at the hip (femoral neck: 0.34SD (95%CI: 0.15, 0.54)). Although adjustment for body mass index (BMI) or lean mass index (LMI) at the lumbar spine reduced the size of the difference in BMD between African Caribbean and European men (age and height adjusted difference: 0.35SD (0.08, 0.62); age and BMI adjusted difference: 0.25SD (−0.02, 0.51)), in both men and women ethnic differences remained after adjustment for measures of central adiposity (estimated visceral adipose tissue mass (VAT mass) and android to gynoid ratio) and inflammation (interleukin-6 (logIL-6) and C-reactive protein (logCRP)). Furthermore, in women, we observed ethnic differences in the relationship between BMI (overall interaction: p = 0.04), LMI (p = 0.04) or VAT mass (p = 0.009) and standardised lumbar spine BMD. In this tri-ethnic cohort, ethnic differences in BMD at the femoral neck, total hip or lumbar spine were not explained by BMI, central adiposity or inflammatory status. Given ethnic differences in fracture incidence, it is important to further investigate why ethnic differences in BMD exist. • Ethnic differences in BMD in a UK tri-ethnic cohort of men and women exist. • In women associations between adiposity and spine BMD differed across ethnic groups. • Ethnic differences in BMD were not explained by BMI, adiposity or inflammation. [ABSTRACT FROM AUTHOR]

This study explores the relationship between musculoskeletal conditions of ageing and life-space mobility (LSM) in 1110 community-dwelling older adults from the Hertfordshire Cohort Study. LSM is a novel measure which captures ability to mobilise within the home, locally and more widely. Among men, older age, care receipt, not driving a car, lower wellbeing, and reduced physical function were associated with lower LSM, while in women only driving status and physical function were associated with LSM. Osteoporosis, arthritis, and fractures had no significant associations with LSM in either gender. These findings provide support for sex-specificity in the determinants of LSM and inform novel approaches to improving mobility and health in older age. • Life-space mobility (LSM) is essential for engagement in activities and maintaining independence. • Mobility declines with age and is associated with adverse health outcomes. • This study investigates gender differences in the relationships between musculoskeletal factors and LSM among older adults. • Musculoskeletal conditions and fractures were not associated with LSM. • Age, receipt of care, falls wellbeing, and physical function were associated with LSM in men; only physical function was associated with LSM in women. [ABSTRACT FROM AUTHOR]

This study examined whether the association of quality of life (QoL) with perceived neighbourhood problems is stronger in older adults with osteoarthritis (OA) than in those without OA. Of all 294 participants, 23.8% had OA. More perceived neighbourhood problems were associated with a stronger decrease in QoL over time in participants with OA (B=-0.018; p=0.02) than in those without OA (B=-0.004; p=0.39). Physical activity did not mediate this relationship. Older adults with OA may be less able to deal with more challenging environments. [ABSTRACT FROM AUTHOR]

Traditional analysis of High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) images results in a multitude of cortical and trabecular parameters which would be potentially cumbersome to interpret for clinicians compared to user-friendly tools utilising clinical parameters. A computer vision approach (by which the entire scan is 'read' by a computer algorithm) to ascertain fracture risk, would be far simpler. We therefore investigated whether a computer vision and machine learning technique could improve upon selected clinical parameters in assessing fracture risk. Participants of the Hertfordshire Cohort Study (HCS) attended research visits at which height and weight were measured; fracture history was determined via self-report and vertebral fracture assessment. Bone microarchitecture was assessed via HR-pQCT scans of the non-dominant distal tibia (Scanco XtremeCT), and bone mineral density measurement and lateral vertebral assessment were performed using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Images were cropped, pre-processed and texture analysis was performed using a three-dimensional local binary pattern method. These image data, together with age, sex, height, weight, BMI, dietary calcium and femoral neck BMD, were used in a random-forest classification algorithm. Receiver operating characteristic (ROC) analysis was used to compare fracture risk identification methods. Overall, 180 males and 165 females were included in this study with a mean age of approximately 76 years and 97 (28 %) participants had sustained a previous fracture. Using clinical risk factors alone resulted in an area under the curve (AUC) of 0.70 (95 % CI: 0.56–0.84), which improved to 0.71 (0.57–0.85) with the addition of DXA-measured BMD. The addition of HR-pQCT image data to the machine learning classifier with clinical risk factors and DXA-measured BMD as inputs led to an improved AUC of 0.90 (0.83–0.96) with a sensitivity of 0.83 and specificity of 0.74. These results suggest that using a three-dimensional computer vision method to HR-pQCT scanning may enhance the identification of those at risk of fracture beyond that afforded by clinical risk factors and DXA-measured BMD. This approach has the potential to make the information offered by HR-pQCT more accessible (and therefore) applicable to healthcare professionals in the clinic if the technology becomes more widely available. • HR-pQCT scans produce many parameters, which may be unwieldy in clinical practice. • Computer vision was applied to HR-pQCT scans to discriminate previous fractures. • This improved fracture discrimination compared to using BMD and clinical factors. [ABSTRACT FROM AUTHOR]

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72–81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p < 0.01), cortical thickness (p < 0.05) and trabecular number (p < 0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p < 0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations. [ABSTRACT FROM AUTHOR]

The age-related loss of skeletal muscle mass and strength is associated with adverse health outcomes. However, to date, peripheral quantitative computed tomography (pQCT)-derived muscle density has been little studied. We used a well characterised cohort of older adults to identify lifestyle and anthropometric determinants of pQCT-derived muscle density measured 11 years later, and to report relationships between pQCT-derived muscle density with history of falls and prevalent fractures. A lifestyle questionnaire was administered to 197 men and 178 women, aged 59–70 at baseline. After a median of 11.5 (IQR 10.9, 12.3) years, pQCT (Stratec XCT2000) of the radius and tibia was performed to measure forearm muscle density (FMD) and calf muscle density (CMD). Presence of falls and fractures since the age of 45 were determined through participant recall; vertebral fractures were also ascertained through vertebral fracture assessment using iDXA. Total hip BMD (TH aBMD) was assessed using DXA. Baseline characteristics in relation to muscle density at follow-up were examined using linear regression; associations between muscle density and prior falls and fractures were investigated using logistic regression. All analyses were adjusted for sex and age. Mean (SD) age at muscle density measurement was 76.3 (2.6) years. Mean (SD) FMD was 79.9 (3.1) and 77.2 (3.2) among males and females, respectively; CMD was 80.7 (2.6) and 78.5 (2.6) among males and females, respectively. Significant sex-differences in muscle density were observed at each site (p < 0.001). Female sex, lower weight, and lower body mass index were associated (p < 0.05) with both lower FMD and CMD. Additional correlates of lower CMD included older age and shorter stature. Lifestyle measures were not associated with muscle density in this cohort. Lower FMD was related to increased risk of previous fracture (odds ratio (95 % CI) per SD lower FMD: 1.42 (1.07, 1.89), p = 0.015) but not after adjustment for TH aBMD (p > 0.08). No significant relationships were seen between muscle density and falls. Female sex, older age, and lower BMI were associated with subsequent lower muscle density in older community-dwelling adults. Lower FMD was related to increased risk of previous fracture. Changes in muscle density over time might precede adverse outcomes such as falls and fractures and may be a long-term predictor of frailty. It could be also suggested that muscle density could be a more clinically meaningful surrogate of functional decline and disability than muscle size or mass, but more studies are needed to support this notion. • Muscle density was measured in the arm and calf using pQCT techniques • Baseline correlates of both lower arm and calf muscle density included female sex, lower weight, and lower body mass index • Lifestyle factors were not associated with muscle density in this cohort of community-dwelling older adults • Muscle density in upper limbs was associated with previous fracture rather than falls • Older age and shorter stature were correlated with lower calf muscle density only [ABSTRACT FROM AUTHOR]

Introduction Although it has been suggested that overweight and obese children have an increased risk of fracture, recent studies in post-menopausal women have shown that the relationship between obesity and fracture risk varies by fracture site. We therefore assessed whether adiposity and overweight/obesity prevalence differed by upper limb fracture site in children. Methods Height, weight, BMI, triceps and subscapular skinfold thickness (SFT) were measured in children aged 3–18 years with an acute upper limb fracture. Data was compared across three fracture sites (hand, forearm and upper arm/shoulder [UA]), and to published reference data. Results 401 children (67.1% male, median age 11.71 years, range 3.54–17.27 years) participated. 34.2%, 50.6% and 15.2% had fractures of the hand, forearm and UA, respectively. Children with forearm fractures had higher weight, BMI, subscapular SFT and fat percentage z-scores than those with UA fractures (p < 0.05 for all). SFT and fat percentage z-scores were also higher in children with forearm fractures compared to hand fractures, but children with hand and UA fractures did not differ. Overweight and obesity prevalence was higher in children with forearm fractures (37.6%) than those with UA fractures (19.0%, p = 0.009). This prevalence was also higher than the published United Kingdom population prevalence (27.9%, p = 0.003), whereas that of children with either UA (p = 0.13) or hand fractures (29.1%, p = 0.76) did not differ. These differences in anthropometry and overweight/obesity prevalence by fracture site were evident in boys, but not present in girls. Conclusion Measurements of adiposity and the prevalence of overweight/obesity differ by fracture site in children, and in particular boys, with upper limb fractures. [ABSTRACT FROM AUTHOR]

Background Studies in childhood suggest that both body composition and early postnatal growth are associated with bone mineral density (BMD). However, little is known of the relationships between longitudinal changes in fat (FM) and lean mass (LM) and bone development in pre-pubertal children. We therefore investigated these associations in a population-based mother-offspring cohort, the Southampton Women's Survey. Methods Total FM and LM were assessed at birth and 6–7 years of age by dual-energy x-ray absorptiometry (DXA). At 6–7 years, total cross-sectional area (CSA) and trabecular volumetric BMD (vBMD) at the 4% site (metaphysis) of the tibia was assessed using peripheral quantitative computed tomography [pQCT (Stratec XCT-2000)]. Total CSA, cortical CSA, cortical vBMD and strength–strain index (SSI) were measured at the 38% site (diaphysis). FM, LM and bone parameters were adjusted for age and sex and standardised to create within-cohort z-scores. Change in LM (ΔLM) or FM (ΔFM) was represented by change in z -score from birth to 7 years old and conditioned on the birth measurement. Linear regression was used to explore the associations between ΔLM or ΔFM and standardised pQCT outcomes, before and after mutual adjustment and for linear growth. The β -coefficient represents SD change in outcome per unit SD change in predictor. Results DXA at birth, in addition to both DXA and pQCT scans at 6–7 years, were available for 200 children (48.5% male). ΔLM adjusted for ΔFM was positively associated with tibial total CSA at both the 4% ( β = 0.57SD/SD, p < 0.001) and 38% sites ( β = 0.53SD/SD, p < 0.001), cortical CSA ( β = 0.48SD/SD, p < 0.001) and trabecular vBMD ( β = 0.30SD/SD, p < 0.001), but not with cortical vBMD. These relationships persisted after adjustment for linear growth. In contrast, ΔFM adjusted for ΔLM was only associated with 38% total and cortical CSA, which became non-significant after adjustment for linear growth. Conclusion In this study, gain in childhood LM was positively associated with bone size and trabecular vBMD at 6–7 years of age. In contrast, no relationships between change in FM and bone were observed, suggesting that muscle growth, rather than accrual of fat mass, may be a more important determinant of childhood bone development. [ABSTRACT FROM AUTHOR]

Abstract: High bone mass (HBM), detected in 0.2% of DXA scans, is characterised by a mild skeletal dysplasia largely unexplained by known genetic mutations. We conducted the first systematic assessment of the skeletal phenotype in unexplained HBM using pQCT in our unique HBM population identified from screening routine UK NHS DXA scans. pQCT measurements from the mid and distal tibia and radius in 98 HBM cases were compared with (i) 65 family controls (constituting unaffected relatives and spouses), and (ii) 692 general population controls. HBM cases had substantially greater trabecular density at the distal tibia (340 [320, 359] mg/cm3), compared to both family (294 [276, 312]) and population controls (290 [281, 299]) (p <0.001 for both, adjusted for age, gender, weight, height, alcohol, smoking, malignancy, menopause, steroid and estrogen replacement use). Similar results were obtained at the distal radius. Greater cortical bone mineral density (cBMD) was observed in HBM cases, both at the midtibia and radius (adjusted p <0.001). Total bone area (TBA) was higher in HBM cases, at the distal and mid tibia and radius (adjusted p <0.05 versus family controls), suggesting greater periosteal apposition. Cortical thickness was increased at the mid tibia and radius (adjusted p <0.001), implying reduced endosteal expansion. Together, these changes resulted in greater predicted cortical strength (strength strain index [SSI]) in both tibia and radius (p <0.001). We then examined relationships with age; tibial cBMD remained constant with increasing age amongst HBM cases (adjusted β −0.01 [−0.02, 0.01], p =0.41), but declined in family controls (−0.05 [−0.03, −0.07], p <0.001) interaction p =0.002; age-related changes in tibial trabecular BMD, CBA and SSI were also divergent. In contrast, at the radius HBM cases and controls showed parallel age-related declines in cBMD and trabecular BMD. HBM is characterised by increased trabecular BMD and by alterations in cortical bone density and structure, leading to substantial increments in predicted cortical bone strength. In contrast to the radius, neither trabecular nor cortical BMD declined with age in the tibia of HBM cases, suggesting attenuation of age-related bone loss in weight-bearing limbs contributes to the observed bone phenotype. [Copyright &y& Elsevier]

Abstract: Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength. We studied 313 men and 318 women born in Hertfordshire between 1931 and 1939 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500). Birthweight and conditional weight at 1 year were strongly related to radial and tibial length in both sexes (p <0.001) and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use, and menopausal status in women. Among men, BMI was strongly positively associated with radial (r =0.46, p =0.001) and tibial (r =0.24, p =0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p =0.0002; tibia: p =0.08) and trabecular BMD (radius: p =0.08; tibia: p =0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p =0.0002; tibia: p =0.001) and trabecular (radius: p =0.008; tibia: p =0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p =0.006; fracture load X: p =0.005; fracture load Y: p =0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p =0.0001), cortical (p <0.005) and trabecular (p =0.0002) BMD, poorer forearm bone strength [polar SSI (p =0.006), fracture load X and Y (p =0.02)], and lower tibial total (p <0.001), cortical (p =0.008), and trabecular (p =0.0001) BMD. We have shown that growth in early life is associated with bone size and strength in a UK population aged 65–73 years. Lifestyle factors were associated with volumetric bone density in this population. [Copyright &y& Elsevier]

Osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci. 115 males and 99 females (aged 72–81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011–2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011–2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age. Previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05). Baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS). [Display omitted] • Data from participants of the Hertfordshire Cohort Study (aged 72–81) were analysed. • Bone parameters were examined in relation to previous fracture and BMD loci. • Previous fracture was related to baseline values of several HR-pQCT parameters. • Previous fracture was only related to changes in trabecular BMD. • Relationships between BMD loci and HR-pQCT parameters were weak. [ABSTRACT FROM AUTHOR]