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1.
J Orthop Res ; 38(12): 2740-2748, 2020 12.
Article in English | MEDLINE | ID: mdl-32162719

ABSTRACT

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


Subject(s)
Child Development , Spine/growth & development , Walking , Cohort Studies , Female , Humans , Infant , Male , Middle Aged , Spine/anatomy & histology
2.
J Bone Miner Res ; 34(3): 455-463, 2019 03.
Article in English | MEDLINE | ID: mdl-30496618

ABSTRACT

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements; accordingly, earlier walking is associated with greater bone strength. However, associations between early life loading and joint shape have not been explored. We therefore examined associations between walking age and hip shape at age 60 to 64 years in 1423 individuals (740 women) from the MRC National Survey of Health and Development, a nationally representative British birth cohort. Walking age in months was obtained from maternal interview at age 2 years. Ten modes of variation in hip shape (HM1 to HM10), described by statistical shape models, were ascertained from DXA images. In sex-adjusted analyses, earlier walking age was associated with higher HM1 and HM7 scores; these associations were maintained after further adjustment for height, body composition, and socioeconomic position. Earlier walking was also associated with lower HM2 scores in women only, and lower HM4 scores in men only. Taken together, this suggests that earlier walkers have proportionately larger (HM4) and flatter (HM1, HM4) femoral heads, wider (HM1, HM4, HM7) and flatter (HM1, HM7) femoral necks, a smaller neck-shaft angle (HM1, HM4), anteversion (HM2, HM7), and early development of osteophytes (HM1). These results suggest that age at onset of walking in infancy is associated with variations in hip shape in older age. Early walkers have a larger femoral head and neck and smaller neck-shaft angle; these features are associated with reduced hip fracture risk, but also represent an osteoarthritic-like phenotype. Unlike results of previous studies of walking age and bone mass, associations in this study were not affected by adjustment for lean mass, suggesting that associations may relate directly to skeletal loading in early life when joint shape changes rapidly. © 2018 American Society for Bone and Mineral Research.


Subject(s)
Bone Density , Femur Neck , Walking , Age Factors , Aged , Female , Femur Neck/metabolism , Femur Neck/physiology , Follow-Up Studies , Humans , Infant , Male , Middle Aged , United Kingdom
3.
J Bone Miner Res ; 34(2): 252-261, 2019 02.
Article in English | MEDLINE | ID: mdl-30347128

ABSTRACT

Leisure-time physical activity (LTPA) is widely recommended for the prevention of osteoporosis and fractures in older populations. However, whether the beneficial effects of LTPA on bone accumulate across life and are maintained even after reduction or cessation of regular PA in later life is unknown. We examined whether LTPA across adulthood was cumulatively associated with volumetric and areal bone mineral density (vBMD, aBMD) at ages 60 to 64 and whether associations were mediated by lean mass. Up to 1498 participants from the Medical Research Council National Survey of Health and Development were included in analyses. LTPA was self-reported at ages 36, 43, 53, and 60 to 64, and responses summed to generate a cumulative score (range 0 = inactive at all four ages to 8 = most active at all four ages). Total and trabecular vBMD were measured at the distal radius using pQCT and aBMD at the total hip and lumbar spine (L1 to L4) using DXA. Linear regression was used to test associations of the cumulative LTPA score with each bone outcome. After adjustment for height and weight, a 1-unit increase in LTPA score (95% CI) in men was associated with differences of 1.55% (0.78% to 2.31%) in radial trabecular vBMD, 0.83% (0.41% to 1.25%) in total hip aBMD, and 0.97% (0.44% to 1.49%) in spine aBMD. Among women, positive associations were seen for radial trabecular vBMD and total hip aBMD, but only among those of greater weight (LTPA × weight interaction p ≤ 0.01). In men, there was evidence to suggest that lean mass index may partly mediate these associations. These findings suggest that there are cumulative benefits of LTPA across adulthood on BMD in early old age, especially among men. The finding of weaker associations among women suggests that promotion of specific types of LTPA may be needed to benefit bone health in women. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.


Subject(s)
Body Height , Body Weight , Bone Density , Exercise , Lumbar Vertebrae , Osteoporosis , Radius , Adult , Female , Humans , Lumbar Vertebrae/metabolism , Lumbar Vertebrae/pathology , Lumbar Vertebrae/physiopathology , Male , Middle Aged , Osteoporosis/metabolism , Osteoporosis/pathology , Osteoporosis/physiopathology , Radius/metabolism , Radius/pathology , Radius/physiopathology , United Kingdom
4.
Sci Rep ; 8(1): 16309, 2018 11 05.
Article in English | MEDLINE | ID: mdl-30397263

ABSTRACT

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


Subject(s)
Back Pain/pathology , Spine/pathology , Adult , Back Pain/epidemiology , Cohort Studies , England/epidemiology , Female , Humans , Male , Middle Aged
5.
PLoS One ; 13(6): e0197570, 2018.
Article in English | MEDLINE | ID: mdl-29902185

ABSTRACT

This study investigated associations between measures of adiposity from age 36 and spine shape at 60-64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60-64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60-64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.


Subject(s)
Body Mass Index , Obesity/physiopathology , Overweight/physiopathology , Spine/physiopathology , Absorptiometry, Photon , Adipose Tissue/physiopathology , Adiposity , Adult , Body Composition/physiology , Female , Humans , Male , Middle Aged , Obesity/diagnostic imaging , Overweight/diagnostic imaging , Spine/diagnostic imaging , Waist Circumference/physiology
6.
Integr Cancer Ther ; 17(1): 131-137, 2018 03.
Article in English | MEDLINE | ID: mdl-28110564

ABSTRACT

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


Subject(s)
Breast Neoplasms/therapy , Diet, Healthy , Exercise , Patient Selection , Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Breast Neoplasms/mortality , Diet, Reducing , Female , Healthy Lifestyle , Humans , Life Style , Middle Aged , Overweight/complications , Overweight/therapy
7.
Bone ; 105: 115-121, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28842363

ABSTRACT

OBJECTIVE: To examine the associations of body mass index (BMI) across adulthood with hip shapes at age 60-64years. METHODS: Up to 1633 men and women from the MRC National Survey of Health and Development with repeat measures of BMI across adulthood and posterior-anterior dual-energy X-ray absorptiometry bone mineral density images of the proximal femur recorded at age 60-64 were included in analyses. Statistical shape modelling was applied to quantify independent variations in hip mode (HM), of which the first 6 were examined in relation to: i) BMI at each age of assessment; ii) BMI gain during different phases of adulthood; iii) age first overweight. RESULTS: Higher BMI at all ages (i.e. 15 to 60-64) and greater gains in BMI were associated with higher HM2 scores in both sexes (with positive HM2 values representing a shorter femoral neck and a wider and flatter femoral head). Similarly, younger age first overweight was associated with higher HM2 scores but only in men once current BMI was accounted for. In men, higher BMI at all ages was also associated with lower HM4 scores (with negative HM4 values representing a flatter femoral head, a wider neck and smaller neck shaft angle) but no associations with BMI gain or prolonged exposure to high BMI were found. Less consistent evidence of associations was found between BMI and the other four HMs. CONCLUSION: These results suggest that BMI across adulthood may be associated with specific variations in hip shapes in early old age.


Subject(s)
Body Mass Index , Hip/anatomy & histology , Parturition , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Young Adult
8.
J Anat ; 231(2): 248-259, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28561274

ABSTRACT

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


Subject(s)
Hip Joint/anatomy & histology , Lumbar Vertebrae/anatomy & histology , Absorptiometry, Photon , Bone Density , Cohort Studies , Female , Hip Joint/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Sex Characteristics , Surveys and Questionnaires
9.
J Cachexia Sarcopenia Muscle ; 8(4): 598-606, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28474432

ABSTRACT

BACKGROUND: Ageing is associated with sarcopenia, osteoporosis, and increased fall risk, all of which contribute to increased fracture risk. Mechanically, bone strength adapts in response to forces created by muscle contractions. Adaptations can be through changes in bone size, geometry, and bending strength. Muscle mass is often used as a surrogate for muscle force; however, force can be increased without changes in muscle mass. Increased fall risk with ageing has been associated with a decline in muscle power-which is a measure of mobility. The aims of this study were as follows: (i) to investigate the relationship between muscle parameters in the upper and lower limbs with age in UK men and the influence of ethnicity on these relationships; (ii) to examine the relationships between jump force/grip strength/cross-sectional muscle area (CSMA) with bone outcomes at the radius and tibia. METHODS: White European, Black Afro-Caribbean, and South Asian men aged 40-79 years were recruited from Manchester, UK. Cortical bone mineral content, cross-sectional area, cortical area, cross-sectional moment of inertia, and CSMA were measured at the diaphysis of the radius and tibia using peripheral quantitative computed tomography. Lower limb jump force and power were measured from a single two-legged jump performed on a ground-reaction force platform. Grip strength was measured using a dynamometer. Associations between muscle and bone outcomes was determined using linear regression with adjustments for age, height, weight, and ethnicity. RESULTS: Three hundred and one men were recruited. Jump force was negatively associated with age; for every 10 year increase in age, there was a 4% reduction in jump force (P < 0.0001). There was a significant age-ethnicity interaction for jump power (P = 0.039); after adjustments, this was attenuated (P = 0.088). For every 10 year increase in age, grip strength decreased by 11%. Jump force was positively associated with tibial bone outcomes: a 1 standard deviation greater jump force was associated with significantly higher cortical bone mineral content 3.1%, cross-sectional area 4.2%, cortical area 3.4%, and cross-sectional moment of inertia 6.8% (all P < 0.001). Cross-sectional muscle area of the lower leg was not associated with tibial bone outcomes. Both grip strength and CSMA of the arm were positively associated, to a similar extent, with radius diaphyseal bone outcomes. CONCLUSIONS: Jump force and power are negatively associated with age in UK men. In the lower limb, the measurement of jump force is more strongly related to bone outcomes than CSMA. It is important to consider jump force and power when understanding the aetiology of bone loss and mobility in ageing men.


Subject(s)
Bone and Bones/anatomy & histology , Hand Strength/physiology , Muscle Strength/physiology , Muscles/anatomy & histology , Adult , Aged , Anatomy, Cross-Sectional , Bone Density/physiology , Ethnicity , Exercise/physiology , Humans , Male , Middle Aged , Tibia/anatomy & histology , United Kingdom/epidemiology
10.
J Bone Miner Res ; 32(6): 1209-1217, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28181695

ABSTRACT

Later age at onset of independent walking is associated with lower leg bone strength in childhood and adolescence. However, it is unknown whether these associations persist into older age or whether they are evident at axial (central) or upper limb sites. Therefore, we examined walking age obtained at age 2 years and bone outcomes obtained by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at ages 60 to 64 years in a nationally representative cohort study of British people, the MRC National Survey of Health and Development. It was hypothesized that later walking age would be associated with lower bone strength at all sites. Later independent walking age was associated with lower height-adjusted hip (standardized regression coefficients with 95% confidence interval [CI] -0.179 [-0.251 to -0.107]), spine (-0.157 [-0.232 to -0.082]), and distal radius (-0.159 [-0.245 to -0.073]) bone mineral content (BMC, indicating bone compressive strength) in men (all p < 0.001). Adjustment for covariates partially attenuated these associations, primarily because of lower lean mass and adolescent sporting ability in later walkers. These associations were also evident for a number of hip geometric parameters (including cross-sectional moment of inertia [CSMI], indicating bone bending/torsional strength) assessed by hip structural analysis (HSA) from DXA scans. Similar height-adjusted associations were also observed in women for several hip, spine, and upper limb outcomes, although adjustment for fat or lean mass led to complete attenuation for most outcomes, with the exception of femoral shaft CSMI and spine bone area (BA). In conclusion, later independent walking age appears to have a lifelong association with bone strength across multiple skeletal sites in men. These effects may result from direct effects of early life loading on bone growth and mediation by adult body composition. Results suggest that late walking age may represent a novel risk factor for subsequent low bone strength. Existing interventions effective in hastening walking age may have positive effects on bone across life. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.


Subject(s)
Bone and Bones/physiopathology , Fractures, Bone/physiopathology , Walking/physiology , Absorptiometry, Photon , Adolescent , Age of Onset , Aged , Biochemical Phenomena , Bone and Bones/diagnostic imaging , Child , Child, Preschool , Female , Fractures, Bone/diagnostic imaging , Humans , Male , Middle Aged , Tomography, X-Ray Computed
11.
J Bone Miner Res ; 32(1): 172-180, 2017 01.
Article in English | MEDLINE | ID: mdl-27490028

ABSTRACT

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


Subject(s)
Body Size , Bone and Bones/anatomy & histology , Densitometry , Absorptiometry, Photon , Adolescent , Anthropometry , Bone Density , Child , Child, Preschool , Female , Humans , Lumbar Vertebrae/physiology , Male , Phantoms, Imaging , Reference Values , Young Adult
12.
Age Ageing ; 46(4): 635-641, 2017 07 01.
Article in English | MEDLINE | ID: mdl-27852598

ABSTRACT

Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health. Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre. Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05). Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.


Subject(s)
Bone Density , Bone and Bones/physiopathology , Frailty/physiopathology , Men's Health , Absorptiometry, Photon , Accidental Falls , Adult , Aged , Bone and Bones/diagnostic imaging , Europe , Fractures, Bone/etiology , Fractures, Bone/physiopathology , Fractures, Bone/prevention & control , Frailty/complications , Frailty/diagnostic imaging , Geriatric Assessment , Health Surveys , Humans , Linear Models , Male , Middle Aged , Risk Factors , Ultrasonography
13.
Nat Rev Clin Oncol ; 14(3): 169-186, 2017 03.
Article in English | MEDLINE | ID: mdl-27725679

ABSTRACT

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


Subject(s)
Biomarkers, Tumor , Neoplasms/diagnosis , Clinical Decision-Making , Cost-Benefit Analysis , Fluorodeoxyglucose F18 , Folic Acid/analogs & derivatives , Humans , Neoplasms/economics , Organotechnetium Compounds , Positron-Emission Tomography/methods , Prognosis , Radiopharmaceuticals , Reproducibility of Results , Research Design/standards , Selection Bias
14.
Semin Musculoskelet Radiol ; 20(3): 254-268, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27741541

ABSTRACT

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


Subject(s)
Bone Density , Bone Diseases/diagnostic imaging , Diagnostic Imaging/methods , Absorptiometry, Photon , Adolescent , Bone and Bones/diagnostic imaging , Child , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Ultrasonography
15.
Int J Epidemiol ; 45(4): 1113-1124, 2016 08.
Article in English | MEDLINE | ID: mdl-27401728

ABSTRACT

OBJECTIVES: To investigate the effect of pubertal timing, assessed in adolescence, on bone size, strength and density in men and women in early old age. DESIGN: A British birth cohort study with prospective indicators of pubertal timing based on age at menarche, clinical assessment of pubertal stage, and growth tempo from serial height measures, and bone measures derived from peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) at 60-64 years of age among 866 women and 792 men. METHODS: A first set of regression models investigated the relationships between pubertal timing and bone size, strength and density, adjusting for current height and weight, smoking and adult socioeconomic position. To make an equivalent comparison between men and women, the percentage difference in bone outcomes was calculated for a 5-year difference in age at menarche, and in men a comparison between those who were fully mature or pre-adolescent at 14.5 years. A second set of models investigated the percentage difference in bone outcomes for a 5-year difference in timing of peak height velocity (height tempo) derived from longitudinal growth modelling (Superimposition by Translation and Rotation model; SITAR). RESULTS: After adjustment for current height and weight, a 5-year increase in age at menarche was associated with an 8% [95% confidence interval (CI) -17%, 0.5%, P = 0.07) lower trabecular volumetric bone mineral density (vBMD); men who were pre-adolescent at 14.5 years had a 9%, (95% CI -14%, -4%; P = 0.001) lower trabecular vBMD compared with those who had been fully mature. Other confounders did not attenuate these estimates further. Patterns of association were similar but somewhat weaker for lumbar spine and total hip areal BMD. Age at peak height velocity was associated with even larger differences in BMD in men and women, and was negatively associated with bone size and strength. CONCLUSIONS: The association between later puberty and lower BMD persists into early old age. The 9-10% lower trabecular vBMD in later compared with earlier maturers could be clinically important given a rate of bone loss from midlife of 1-2% a year and the negative association between BMD and fracture.


Subject(s)
Bone Density , Osteoporosis/diagnostic imaging , Puberty/physiology , Absorptiometry, Photon , Adolescent , Body Weight , Female , Fractures, Bone/etiology , Humans , Male , Middle Aged , Phenotype , Prospective Studies , Regression Analysis , Risk Assessment , Social Class , Tomography, X-Ray Computed , United Kingdom
16.
J Clin Endocrinol Metab ; 101(8): 3105-13, 2016 08.
Article in English | MEDLINE | ID: mdl-27228370

ABSTRACT

CONTEXT: Vitamin D is essential for bone health in adolescence, when there is rapid bone mineral content accrual. Because cutaneous sun exposure provides vitamin D, there is no recommended oral intake for UK adolescents. OBJECTIVE: Our objective was to assess seasonal vitamin D status and its contributors in white Caucasian adolescents and examine bone health in those found deficient. DESIGN: Prospective cohort study was undertaken. SETTING: Six schools in Greater Manchester, UK, were included. PARTICIPANTS: Participants were 131 adolescents between 12 and 15 years of age. INTERVENTION(S): Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sun exposure, and dietary vitamin D. Adolescents deficient (25OHD <10 ng/ml/25 nmol/liter) in at least one season underwent dual-energy X-ray absorptiometry (lumbar spine, femoral neck), with bone mineral apparent density correction for size, and peripheral quantitative computed tomography (distal radius) for volumetric bone mineral density (BMD). MAIN OUTCOME MEASURE: Serum 25OHD and BMD measurements. RESULTS: Mean 25OHD was highest in September: 24.1 (SD, 6.9) ng/ml and lowest in January: 15.5 (5.9) ng/ml. Over the year, 16% were deficient in ≥ one season and 79% insufficient (25OHD <20 ng/ml/50 nmol/liter) including 28% in September. Dietary vitamin D was low year-round, whereas personal sun exposure was seasonal and predominantly across the school week. Holidays accounted for 17% variation in peak 25OHD (P < .001). Nineteen adolescents underwent bone assessment, which showed low femoral neck bone mineral apparent density vs matched reference data (P = .0002), three with Z less than or equal to -2.0 distal radius trabecular volumetric BMD. CONCLUSIONS: Sun exposure levels failed to provide adequate vitamin D, with approximately one-quarter of adolescents insufficient even at summer peak. Seasonal vitamin D deficiency was prevalent and those affected had low BMD. Recommendations on vitamin D acquisition are indicated in this age-group.


Subject(s)
Bone Density , Health Behavior , Occupational Exposure/statistics & numerical data , Seasons , Sunlight , Vitamin D Deficiency/epidemiology , Adolescent , Adolescent Behavior , Child , Female , Humans , Male , Nutritional Status/physiology , United Kingdom/epidemiology , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood
17.
J Bone Miner Res ; 31(6): 1167-76, 2016 06.
Article in English | MEDLINE | ID: mdl-26817442

ABSTRACT

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


Subject(s)
Aging/metabolism , Bone Density , Diet, Western , Adult , Aging/pathology , Female , Humans , Male , Middle Aged , Sex Factors , United Kingdom
18.
J Clin Densitom ; 19(1): 54-62, 2016.
Article in English | MEDLINE | ID: mdl-26412139

ABSTRACT

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


Subject(s)
Spinal Fractures/diagnosis , Absorptiometry, Photon , Humans , Magnetic Resonance Imaging , Radionuclide Imaging , Tomography, X-Ray Computed
19.
Radiographics ; 35(7): 2108-20, 2015.
Article in English | MEDLINE | ID: mdl-26562240

ABSTRACT

Human mummies have long been studied by using imaging as a primary investigative method. Mummified animal remains from ancient Egypt are less well researched, yet much can be learned about species diversity and the methods of preservation. Noninvasive imaging methods enable mummy bundles to remain intact, with no detrimental physical effects, thus ensuring protection of a valuable archaeological resource. This article is based on the research experience gathered during 13 years (2000-2012) with 152 animal mummies held in the collections of 17 museums in the United Kingdom. Conventional radiography, computed radiography, digital radiography, and computed tomography (CT) available in the clinical setting were used to assess the value of each imaging modality in the study of animal mummies and related material. Radiography proved to be an excellent research method that provided initial insight into the contents of the mummy bundle, and CT contributed additional useful detail in some cases. Paleoradiologic analyses enabled information on mummy bundle contents to be proved, including the nature of the skeletal remains and the methods of mummification. An optimum method involving radiography and CT is described.


Subject(s)
Mummies/diagnostic imaging , Age Determination by Skeleton/veterinary , Animals , Cause of Death , Egypt, Ancient , Embalming/history , Embalming/methods , Funeral Rites/history , History, Ancient , Mummies/history , Museums , Pets/history , Radiographic Image Enhancement/methods , Religion/history , Retrospective Studies , Tomography, X-Ray Computed/methods
20.
J Cachexia Sarcopenia Muscle ; 6(3): 242-52, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26401471

ABSTRACT

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

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