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Showing papers by "Cyrus Cooper published in 2014"


Journal ArticleDOI
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.

1,383 citations


Journal ArticleDOI
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

875 citations


Journal ArticleDOI
04 Dec 2014-PLOS ONE
TL;DR: This is the first study to provide normative data for grip strength across the life course and these centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.
Abstract: Introduction: Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol. Methods: We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing). Results: Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males’ peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses

636 citations


Journal ArticleDOI
TL;DR: The effect of age is greatest in the elderly for knee and hip OA, but around the menopause for hand OA; OA clusters within individuals, with higher risk of incident knee and Hip disease from prevalent lower limb andHand OA.
Abstract: Objectives Data on the incidence of symptomatic osteoarthritis (OA) are scarce. We estimated incidence of clinical hip, knee and hand OA, and studied the effect of prevalent OA on joint-specific incident OA. Methods SIDIAP contains primary care records for>5 million people from Catalonia (Spain). Participants aged ≥40 years with an incident diagnosis of knee, hip or hand OA between 2006 and 2010 were identified using International Classification of Diseases (ICD)-10 codes. Incidence rates and female-to-male rate ratios (RRs) for each joint site were calculated. Age, gender and body mass index-adjusted HR for future joint-specific OA according to prevalent OA at other sites were estimated using Cox regression. Results 3 266 826 participants were studied for a median of 4.45 years. Knee and hip OA rates increased continuously with age, and female-to-male RRs were highest at age 70–75 years. In contrast, female hand OA risk peaked at age 60–64 years, and corresponding female-to-male RR was highest at age 50–55 years. Adjusted HR for prevalent knee OA on risk of hip OA was 1.35 (99% CI 1.28 to 1.43); prevalent hip OA on incident knee OA: HR 1.15 (1.08 to 1.23). Prevalent hand OA predicted incident knee and hip OA: HR 1.20 (1.14 to 1.26) and 1.23 (1.13 to 1.34), respectively. Conclusions The effect of age is greatest in the elderly for knee and hip OA, but around the menopause for hand OA. OA clusters within individuals, with higher risk of incident knee and hip disease from prevalent lower limb and hand OA.

510 citations



Journal ArticleDOI
TL;DR: Preschool-aged children meet current physical activity guidelines, but with the majority of their active time spent in LPA, investigation of the importance of activity intensity in younger children is needed.
Abstract: Background Little is known about preschool-aged children’s levels of physical activity (PA) over the course of the day. Using time-stamped data, we describe the levels and patterns of PA in a population-based sample of four-year-old British children.

376 citations


Journal ArticleDOI
TL;DR: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods, and further research on explanations for the methodological differences is required.

370 citations


Journal ArticleDOI
Karani Santhanakrishnan Vimaleswaran1, Karani Santhanakrishnan Vimaleswaran2, Alana Cavadino1, Diane J. Berry1, Rolf Jorde3, Aida Karina Dieffenbach4, Chen Lu5, Alexessander Couto Alves6, Alexessander Couto Alves7, Hiddo J.L. Heerspink8, Emmi Tikkanen9, J. G. Eriksson10, Andrew Wong11, Massimo Mangino12, Kathleen A. Jablonski13, Ilja M. Nolte8, Denise K. Houston14, Tarunveer S. Ahluwalia15, Tarunveer S. Ahluwalia16, Peter J. van der Most8, Dorota Pasko17, Lina Zgaga18, Lina Zgaga19, Elisabeth Thiering20, Veronique Vitart19, Ross M. Fraser19, Jennifer E. Huffman19, Rudolf A. de Boer8, Ben Schöttker4, Kai-Uwe Saum4, Mark I. McCarthy21, Mark I. McCarthy22, Josée Dupuis5, Karl-Heinz Herzig23, Karl-Heinz Herzig7, Sylvain Sebert7, Anneli Pouta24, Anneli Pouta23, Jaana Laitinen25, Marcus E. Kleber26, Gerjan Navis8, Mattias Lorentzon10, Karen A. Jameson27, Nigel K Arden27, Nigel K Arden21, Jackie A. Cooper11, Jayshree Acharya11, Rebecca Hardy11, Olli T. Raitakari28, Olli T. Raitakari29, Samuli Ripatti9, Liana K. Billings, Jari Lahti9, Clive Osmond27, Brenda W.J.H. Penninx30, Lars Rejnmark31, Kurt Lohman14, Lavinia Paternoster32, Ronald P. Stolk8, Dena G. Hernandez24, Liisa Byberg33, Emil Hagström33, Håkan Melhus33, Erik Ingelsson34, Erik Ingelsson22, Erik Ingelsson33, Dan Mellström10, Östen Ljunggren33, Ioanna Tzoulaki6, Stela McLachlan19, Evropi Theodoratou19, Carla M. T. Tiesler20, Antti Jula24, Pau Navarro19, Alan F. Wright19, Ozren Polasek35, James F. Wilson19, Igor Rudan19, Veikko Salomaa24, Joachim Heinrich, Harry Campbell19, Jacqueline F. Price19, Magnus Karlsson36, Lars Lind33, Karl Michaëlsson33, Stefania Bandinelli, Timothy M. Frayling17, Catharina A. Hartman8, Thorkild I. A. Sørensen37, Thorkild I. A. Sørensen16, Stephen B. Kritchevsky14, Bente L. Langdahl31, Johan G. Eriksson, Jose C. Florez38, Tim D. Spector12, Terho Lehtimäki39, Diana Kuh11, Steve E. Humphries11, Cyrus Cooper27, Cyrus Cooper21, Claes Ohlsson10, Winfried März40, Winfried März26, Winfried März41, Martin H. de Borst8, Meena Kumari11, Mika Kivimäki11, Thomas J. Wang42, Chris Power1, Hermann Brenner4, Guri Grimnes3, Pim van der Harst8, Harold Snieder8, Aroon D. Hingorani11, Stefan Pilz41, John C. Whittaker43, Marjo-Riitta Järvelin, Elina Hyppönen1, Elina Hyppönen44 
TL;DR: In this article, the authors used a mendelian randomisation approach to test whether low plasma 25-hydroxyvitamin D (25[OH]D) concentration is causally associated with blood pressure and hypertension risk.

320 citations


Journal ArticleDOI
TL;DR: The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy, and modest positive relationships were identified between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations.
Abstract: Background It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved. Objectives To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective? Methods We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers. Inclusion and exclusion criteria Subjects: pregnant women or pregnant women and their offspring. Exposure: either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). Outcomes: offspring – birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother – pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis. Results Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5. Limitations Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition. Conclusions The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required. Study registration This study is registered as PROSPERO CRD42011001426. Funding The National Institute for Health Research Health Technology Assessment programme.

309 citations


Journal ArticleDOI
TL;DR: In this paper, a double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis.
Abstract: Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis. Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5–5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: −0.23 (SD 0.56) mm; 2 g/day: −0.27 (SD 0.63) mm; placebo: −0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.

260 citations


Journal ArticleDOI
TL;DR: Current Medical Research Council (MRC) Population Health Sciences Research Network (PHSRN) funded work to develop guidance for process evaluations of complex public health interventions is described.
Abstract: Public health interventions aim to improve the health of populations or at-risk subgroups. Problems targeted by such interventions, such as diet and smoking, involve complex multifactorial aetiology. Interventions will often aim to address more than one cause simultaneously, targeting factors at multiple levels (eg, individual, interpersonal, organisational), and comprising several components which interact to affect more than one outcome.1 They will often be delivered in systems which respond in unpredictable ways to the new intervention.2 Recognition is growing that evaluations need to understand this complexity if they are to inform future intervention development, or efforts to apply the same intervention in another setting or population.1 Achieving this will require evaluators to move beyond a ‘does it work?’ focus, towards combining outcomes and process evaluation. There is no such thing as a typical process evaluation, with the term applied to studies which range from a few simple quantitative items on satisfaction, to complex mixed-method studies exploring issues such as the process of implementation, or contextual influences on implementation and outcomes. As recognised within MRC guidance for evaluating complex interventions, process evaluation may be used to ‘assess fidelity and quality of implementation, clarify causal mechanisms and identify contextual factors associated with variation in outcomes’.1 This paper briefly discusses each of these core aims for process evaluation, before describing current Medical Research Council (MRC) Population Health Sciences Research Network (PHSRN) funded work to develop guidance for process evaluations of complex public health interventions.


Journal ArticleDOI
TL;DR: This article investigated the relationship of weight, BMI, and height with incident clinical fracture in a practice-based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW).
Abstract: Low body mass index (BMI) is a well-established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice-based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self-reported fracture over a 3-year period using the Cox proportional hazards model and fitted the best linear or nonlinear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3-year follow-up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m(2) were 0.80 (0.71-0.90), 0.83 (0.76-0.92), and 0.88 (0.83-0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5-kg increase 1.05 (1.02-1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10-cm increase were 0.85 (0.75-0.97) (p = 0.02) and 0.73 (0.57-0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for nonlinear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site-specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling.


Journal ArticleDOI
Qibin Qi1, Tuomas O. Kilpeläinen2, Mary K. Downer3, Toshiko Tanaka4, Caren E. Smith5, Ivonne Sluijs6, Emily Sonestedt7, Audrey Y. Chu, Frida Renström7, Xiaochen Lin3, Lars H. Ängquist8, Jinyan Huang9, Zhonghua Liu3, Yanping Li3, Muhammad Asif Ali3, Min Xu3, Tarunveer S. Ahluwalia10, Jolanda M. A. Boer11, Peng Chen, Makoto Daimon12, Johan G. Eriksson13, M. Perola14, Yechiel Friedlander15, Yu-Tang Gao9, Denise H. M. Heppe, John W. Holloway16, Denise K. Houston, Stavroula Kanoni17, Yu Mi Kim18, Maarit A. Laaksonen13, Tiina Jääskeläinen19, Nanette R. Lee20, Terho Lehtimäki21, Rozenn N. Lemaitre, Wei Lu, Robert Luben2, Ani Manichaikul22, Satu Männistö13, Pedro Marques-Vidal, Keri L. Monda23, Julius S. Ngwa24, Louis Pérusse25, Frank J. A. van Rooij, Yong-Bing Xiang9, Wanqing Wen26, Mary K. Wojczynski27, Jingwen Zhu28, Ingrid B. Borecki27, Claude Bouchard29, Qiuyin Cai26, Cyrus Cooper30, Cyrus Cooper16, Cyrus Cooper31, George Dedoussis32, Panos Deloukas17, Luigi Ferrucci4, Nita G. Forouhi2, Torben Hansen33, Lene Christiansen14, Albert Hofman, Ingegerd Johansson34, Torben Jørgensen35, Shigeru Karasawa36, Kay-Tee Khaw2, Mi Kyung Kim37, Kati Kristiansson13, Huaixing Li28, Xu Lin28, Yongmei Liu, Kurt Lohman38, Jirong Long26, Vera Mikkilä2, Dariush Mozaffarian2, Kari E. North, Oluf Pedersen33, Olli T. Raitakari39, Harri Rissanen13, Jaakko Tuomilehto14, Yvonne T. van der Schouw6, André G. Uitterlinden14, M. Carola Zillikens40, Oscar H. Franco, E. Shyong Tai41, Xiao-Ou Shu26, David S. Siscovick27, Ulla Toft35, W M Monique Verschuren11, Peter Vollenweider42, Nicholas J. Wareham2, Jacqueline C.M. Witteman, Wei Zheng26, Paul M. Ridker, Jae H. Kang, Liming Liang3, Majken K. Jensen3, Gary C. Curhan2, Louis R. Pasquale14, David J. Hunter3, Karen L. Mohlke43, Matti Uusitupa19, L. Adrienne Cupples14, Tuomo Rankinen29, Marju Orho-Melander7, Tao Wang1, Daniel I. Chasman3, Paul W. Franks14, Thorkild I. A. Sørensen8, Frank B. Hu3, Ruth J. F. Loos14, Jennifer A. Nettleton14, Lu Qi14 
TL;DR: A positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake is suggested and insight is offered into potential link between FTO, dietaryprotein intake and adiposity.
Abstract: FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

Journal ArticleDOI
TL;DR: In this paper, the authors used an updated systematic review to examine the performance characteristics of serum procollagen type I N propeptide (s-PINP) and serum C-terminal cross-linking telopeptide of type I collagen (S-CTX) in fracture risk prediction in untreated individuals in prospective cohort studies.
Abstract: The aim of this report was to summarize the clinical performance of two reference bone turnover markers (BTMs) in the prediction of fracture risk. We used an updated systematic review to examine the performance characteristics of serum procollagen type I N propeptide (s-PINP) and serum C-terminal cross-linking telopeptide of type I collagen (s-CTX) in fracture risk prediction in untreated individuals in prospective cohort studies. We excluded cross-sectional studies. Ten potentially eligible publications were identified and six included in the meta-analysis. There was a significant association between s-PINP and the risk of fracture. The hazard ratio per SD increase in s-PINP (gradient of risk [GR]) was 1.23 (95 % CI 1.09–1.39) for men and women combined unadjusted for bone mineral density. There was also a significant association between s-CTX and risk of fracture, GR = 1.18 (95 % CI 1.05–1.34) unadjusted for bone mineral density. For the outcome of hip fracture, the association between s-CTX and risk of fracture was slightly higher, 1.23 (95 % CI 1.04–1.47). Thus, there is a modest but significant association between BTMs and risk of future fractures.

Journal ArticleDOI
TL;DR: Testing of pregnancy interventions aimed at optimizing offspring bone health is now underway, and it is hoped that through such programs, novel public health strategies may be established with the ultimate goal of reducing the burden of osteoporotic fracture in older age.
Abstract: It is becoming increasingly apparent that the risk of developing osteoporosis is accrued throughout the entire lifecourse, even from as early as conception. Thus early growth is associated with bone mass at peak and in older age, and risk of hip fracture. Novel findings from mother-offspring cohorts have yielded greater understanding of relationships between patterns of intrauterine and postnatal growth in the context of later bone development. Study of biological samples from these populations has helped characterize potential mechanistic underpinnings, such as epigenetic processes. Global policy has recognized the importance of early growth and nutrition to the risk of developing adult chronic noncommunicable diseases such as osteoporosis; testing of pregnancy interventions aimed at optimizing offspring bone health is now underway. It is hoped that through such programs, novel public health strategies may be established with the ultimate goal of reducing the burden of osteoporotic fracture in older age.

Journal ArticleDOI
TL;DR: This study supports other international studies by showing changes in the incidence of hip fractures after age-population adjustment, which denotes a decrease in the younger age groups and among women and shows an increase in both groups over 85 years.
Abstract: Temporal trends in hip fracture incidence have recently been reported in some developed countries. Such data in Spain has previously been incomplete; this study reports the stratified incidence of hip fractures in people over 65 in Spain during the last 14 years. The main objective is to establish whether temporal trends in hip fracture incidence in Spain exist. Ecological study with data from hospital discharges nationwide. The study includes patients aged ≥65 years during a 14-year period (1997–2010). The analysis compares two periods of four years: 1997–2000 (P1) and 2007–2010 (P2). There were 119,857 fractures in men and 415,421 in women. Comparing periods (P1 vs P2) over 10 years, the crude incidence rate/100,000 inhabitant/year increased an average of 2.3 %/year in men and 1.4 % in women. After adjustment, the rate increased an average of 0.4 %/year in men (p < 0.0001), but decreased 0.2 %/year in women (p < 0.0001). In men, younger than 85, the decrease was not significant except in 70–74 years, and from 80 years, the adjusted rate increases significantly (p < 0.0001). In women under 80 years of age, the decrease in adjusted rate was significant; there was no change in 80–84 years, and the adjusted rate increased significantly in individuals 85 years and older (p < 0.0001). Mortality rates declined by 22 % in both sexes, and the index of overaging population rises 30.1 % in men and 25.2 % in women. This study supports other international studies by showing changes in the incidence of hip fractures after age-population adjustment, which denotes a decrease in the younger age groups and among women and shows an increase in both groups over 85 years. The increase in the crude incidence rate of hip fracture in Spain reflects changes in population structure.


Journal Article
TL;DR: In this article, the authors used an updated systematic review to examine the performance characteristics of serum procollagen type I N propeptide (s-PINP) and serum C-terminal cross-linking telopeptide of type I collagen (S-CTX) in fracture risk prediction in untreated individuals in prospective cohort studies.
Abstract: The aim of this report was to summarize the clinical performance of two reference bone turnover markers (BTMs) in the prediction of fracture risk. We used an updated systematic review to examine the performance characteristics of serum procollagen type I N propeptide (s-PINP) and serum C-terminal cross-linking telopeptide of type I collagen (s-CTX) in fracture risk prediction in untreated individuals in prospective cohort studies. We excluded cross-sectional studies. Ten potentially eligible publications were identified and six included in the meta-analysis. There was a significant association between s-PINP and the risk of fracture. The hazard ratio per SD increase in s-PINP (gradient of risk [GR]) was 1.23 (95 % CI 1.09–1.39) for men and women combined unadjusted for bone mineral density. There was also a significant association between s-CTX and risk of fracture, GR = 1.18 (95 % CI 1.05–1.34) unadjusted for bone mineral density. For the outcome of hip fracture, the association between s-CTX and risk of fracture was slightly higher, 1.23 (95 % CI 1.04–1.47). Thus, there is a modest but significant association between BTMs and risk of future fractures.

Journal ArticleDOI
TL;DR: Physical activity levels in mothers and their 4-year-old children are directly associated, with associations at different activity intensities influenced by temporal and demographic factors.
Abstract: OBJECTIVES: To investigate the association between objectively measured maternal and preschool-aged children’s physical activity, determine how this association differs by demographic and temporal factors, and identify factors associated with maternal activity levels. METHODS: In the UK Southampton Women’s Survey, physical activity levels of 554 4-year-olds and their mothers were measured concurrently by using accelerometry for ≤7 days. Two-level mixed-effects linear regression was used to model the association between maternal and children’s minutes spent sedentary, in light (LPA) and moderate-to-vigorous physical activity (MVPA). Linear regression was used to investigate correlates of maternal activity. RESULTS: Mother-child daily activity levels were positively associated at all activity intensities (sedentary, LPA, and MVPA; all P CONCLUSIONS: Physical activity levels in mothers and their 4-year-old children are directly associated, with associations at different activity intensities influenced by temporal and demographic factors. Influences on maternal physical activity levels also differ by activity intensity. Providing targeted interventions for mothers of young children may increase both groups’ activity.

Journal ArticleDOI
TL;DR: Uptake of FRAX was high in North America, the Antipodes and most countries of Europe; intermediate in Latin America and the Middle East; and very low in Africa and much of South East Asia.
Abstract: The worldwide uptake of FRAX is described. The aim of this report was to determine the usage of FRAX worldwide over a 1-year period from 1 May 2012. The number of FRAX calculations from each country was assessed over a 1-year period and expressed as calculations per million of the population aged 50 years or more. Countries were colour coded according to usage to populate a world map. Over the index year, there were estimated to be 2,391,639 calculations sourced from 173 counties. Uptake was high in North America, the Antipodes and most countries of Europe; intermediate in Latin America and the Middle East; and very low in Africa and much of South East Asia. It is expected that the comparative data will encourage the development of new FRAX models and the uptake of FRAX into assessment guidelines.


Journal ArticleDOI
Alireza Moayyeri1, Yi-Hsiang Hsu2, David Karasik2, Karol Estrada, Su-Mei Xiao, Carrie M. Nielson, Priya Srikanth, Sylvie Giroux, Scott Wilson3, Scott Wilson4, Scott Wilson5, Hou-Feng Zheng6, Albert V. Smith7, Stephen R Pye8, Paul Leo9, Alexander Teumer, Joo-Yeon Hwang, Claes Ohlsson10, Fiona E. McGuigan, Ryan L. Minster, Caroline Hayward11, José M. Olmos12, Leo-Pekka Lyytikäinen, Joshua R. Lewis5, Joshua R. Lewis4, Karin M. A. Swart, Laura Masi, Christopher Oldmeadow13, Elizabeth G. Holliday13, Sulin Cheng14, Natasja M. van Schoor, Nicholas C. Harvey15, Marcin Kruk, Fabiola Del Greco M16, Wilmar Igl, Olivia Trummer17, Efi Grigoriou18, Robert Luben1, Ching-Ti Liu19, Yanhua Zhou19, Ling Oei20, Carolina Medina-Gomez20, Joseph M. Zmuda21, Gregory J. Tranah22, Gregory J. Tranah23, Suzanne J. Brown4, Frances M K Williams3, Nicole Soranzo24, Johanna Jakobsdottir, Kristin Siggeirsdottir7, Kate L. Holliday8, Anke Hannemann, Min Jin Go, Melissa Garcia25, Ozren Polasek26, Marika Laaksonen27, Kun Zhu5, Kun Zhu4, A.W. Enneman, Mark McEvoy13, Roseanne Peel13, Pak C. Sham28, Maciej Jaworski, Åsa Johansson, Andrew A. Hicks16, Paweł Płudowski, Rodney J. Scott13, Rosalie A. M. Dhonukshe-Rutten29, Nathalie van der Velde, Mika Kähönen30, Jorma Viikari, Harri Sievänen, Olli T. Raitakari31, Olli T. Raitakari32, Jesús González-Macías12, José L. Hernández12, Dan Mellström10, Östen Ljunggren33, Yoon Shin Cho34, Uwe Völker, Matthias Nauck, Georg Homuth, Henry Völzke35, Robin Haring, Matthew A. Brown9, Eugene V. McCloskey25, Eugene V. McCloskey36, Geoffrey C. Nicholson9, Richard Eastell36, John A. Eisman, Graeme Jones37, Ian R. Reid38, Elaine M. Dennison15, John D. Wark39, Steven Boonen40, Dirk Vanderschueren40, Frederick C. W. Wu41, Thor Aspelund7, J. Brent Richards3, J. Brent Richards6, Doug C. Bauer22, Doug C. Bauer23, Albert Hofman20, Kay-Tee Khaw1, George Dedoussis18, Barbara Obermayer-Pietsch17, Ulf Gyllensten, Peter P. Pramstaller16, Roman S. Lorenc, Cyrus Cooper42, Cyrus Cooper15, Annie W.C. Kung, Paul Lips43, Markku Alen44, John Attia13, Maria Luisa Brandi45, Lisette C. P. G. M. de Groot29, Terho Lehtimäki, José A. Riancho12, Harry Campbell11, Yongmei Liu46, Tamara B. Harris25, Kristina Åkesson, Magnus Karlsson47, Jong-Young Lee, Henri Wallaschofski, Emma L. Duncan9, Emma L. Duncan48, Terence W O'Neill8, Vilmundur Gudnason7, Tim D. Spector3, François Rousseau49, Eric S. Orwoll50, Steven R. Cummings22, Steven R. Cummings23, Nicholas J. Wareham1, Fernando Rivadeneira20, André G. Uitterlinden20, Richard L. Prince5, Richard L. Prince4, Douglas P. Kiel2, Jonathan Reeve1, Jonathan Reeve42, Stephen Kaptoge1 
TL;DR: This GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
Abstract: Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

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TL;DR: Perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size–corrected BMC in childhood, and the potential mechanistic and functional significance of this finding remains a subject for further investigation.
Abstract: Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid-X Receptor-alpha (RXRA) is an essential cofactor in the action of 1,25(OH)2-vitamin D, and RXRA methylation in umbilical cord DNA has been associated with later offspring adiposity. We tested the hypothesis that RXRA methylation in umbilical cord DNA collected at birth is associated with offspring skeletal development, assessed by dual-energy X-ray absorptiometry, in a population-based mother-offspring cohort (Southampton Women's Survey). Relationships between maternal plasma 25(OH)-vitamin D concentrations and cord RXRA methylation were also investigated. In 230 children aged 4 years, higher % methylation at 4 out of 6 RXRA CpG sites measured was correlated with lower offspring BMC corrected for body size (??=???2.1 to ?3.4g/SD, p?=?0.002 to 0.047). In a second independent cohort (n?=?64), similar negative associations at two of these CpG sites, but positive associations at the two remaining sites, were observed; however none of the relationships in this replication cohort achieved statistical significance. Maternal free 25(OH)-vitamin D index was negatively associated with methylation at one of these RXRA CpG sites (??=???3.3 SD/unit, p?=?0.03). Thus, perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size-corrected bone mineral content in childhood. The potential mechanistic and functional significance of this finding remains a subject for further investigation.

Journal ArticleDOI
TL;DR: Regular use of NSAIDs appears to eliminate the excess fracture risk related to ankylosing spondylitis, but the mechanisms involved are unknown.
Abstract: The objective of this work was to study the associations between ankylosing spondylitis (AS) and clinical vertebral and nonvertebral fractures. Data from a large population-based public health database in Spain, Sistema d'Informacio per al Desenvolupament de l'Investigacio en Atencio Primaria (SIDIAP), were used in this parallel cohort study. All participants registered in SIDIAP on January 1, 2006, were screened to identify those with a diagnosis of AS. Five age-matched, gender-matched, and general practice surgery–matched controls were selected for each patient with AS. All participants were followed until December 31, 2011, transfer out date, or death date. Fractures during this time were classified as vertebral or nonvertebral. Adjustment was made for potential confounders (tobacco smoking, alcohol consumption, body mass index, and use of oral steroids). Of 4,920,353 eligible patients in SIDIAP, 6474 AS patients with matched controls (n = 32,346) were available. A higher proportion of patients with AS versus controls had clinical vertebral (0.86% versus 0.41%) and nonvertebral (3.4% versus 2.7%) fractures. Adjusted Cox regression models showed an increased risk of clinical vertebral (hazard ratio [HR] 1.93; 95% confidence interval [CI], 1.39 to 2.68; p < 0.001) and nonvertebral (HR 1.19; 95% CI, 1.02 to 1.39; p = 0.03) fractures among patients with AS. However, the observed increased risks were apparent only in those not on regular nonsteroidal anti-inflammatory drugs (NSAIDs). There were no interactions with inflammatory bowel disease, psoriasis, or previous back pain. Patients with AS are at increased risk of vertebral and nonvertebral clinical fractures, independently of various risk factors. Regular use of NSAIDs appears to eliminate the excess fracture risk related to AS, but the mechanisms involved are unknown. © 2014 American Society for Bone and Mineral Research

Journal ArticleDOI
TL;DR: These patients should be considered for particular consultation/follow-up procedures in the effort to convince on the benefits of treatment and to allay fears of adverse drug reactions, since poor adherence is a major problem for the success of a strategy for osteoporosis and limits cost-effectiveness.
Abstract: Summary This consensus article reviews the diagnosis and treatment of osteoporosis in geriatric populations. Specifically, it reviews the risk assessment and intervention thresholds, the impact of nutritional deficiencies, fall prevention strategies, pharmacological treatments and their safety considerations, the risks of sub-optimal treatment adherence and strategies for its improvement.

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TL;DR: A new composite measure of nine variables that can influence food choices was developed to provide an overall assessment of the healthfulness of retail food stores and could be useful in future research to measure the relationship between main food store and quality of diet.
Abstract: Background: The consumer nutrition environment has been conceptualised as in-store environmental factors that influence food shopping habits. More healthful in-store environments could be characterised as those which promote healthful food choices such as selling good quality healthy foods or placing them in prominent locations to prompt purchasing. Research measuring the full-range of in-store environmental factors concurrently is limited. Purpose: To develop a summary score of ‘healthfulness’ composed of nine in-store factors that influence food shopping behaviour, and to assess this score by store type and neighbourhood deprivation. Methods: A cross-sectional survey of 601 retail food stores, including supermarkets, grocery stores and convenience stores, was completed in Hampshire, United Kingdom between July 2010 and June 2011. The survey measured nine variables (variety, price, quality, promotions, shelf placement, store placement, nutrition information, healthier alternatives and single fruit sale) to assess the healthfulness of retail food stores on seven healthy and five less healthy foods that are markers of diet quality. Four steps were completed to create nine individual variable scores and another three to create an overall score of healthfulness for each store. Results: Analysis of variance showed strong evidence of a difference in overall healthfulness by store type (p <0.001). Large and premium supermarkets offered the most healthful shopping environments for consumers. Discount supermarkets, ‘world’, convenience and petrol stores offered less healthful environments to consumers however there was variation across the healthfulness spectrum. No relationship between overall healthfulness and neighbourhood deprivation was observed (p =0.1). Conclusions: A new composite measure of nine variables that can influence food choices was developed to provide an overall assessment of the healthfulness of retail food stores. This composite score could be useful in future research to measure the relationship between main food store and quality of diet, and to evaluate the effects of multi-component food environment interventions.

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TL;DR: Older people in rehabilitation and care home settings had lower grip strength than reported for those living at home, and grip strength varied widely between healthcare settings independent of known major influences.
Abstract: Background: low muscle strength is central to geriatric syndromes including sarcopenia and frailty. It is well described in community-dwelling older people, but the epidemiology of grip strength of older people in rehabilitation or long-term care has been little explored. Objective: to describe grip strength of older people in rehabilitation and nursing home settings. Design: cross-sectional epidemiological study. Setting: three healthcare settings in one town. Subjects: hundred and one inpatients on a rehabilitation ward, 47 community rehabilitation referrals and 100 nursing home residents. Methods: grip strength, age, height, weight, body mass index, number of co-morbidities and medications, Barthel score, MiniMental State Examination (MMSE), nutritional status and number of falls in the last year were recorded. Results: grip strength differed substantially between healthcare settings for both men and women (P< 0.0001). Nursing home residents had the lowest age-adjusted mean grip strength and community rehabilitation referrals the highest. Broadly higher grip strength was associated in univariate analyses with younger age, greater height and weight, fewer comorbidities, higher Barthel score, higher MMSE score, better nutritional status and fewer falls. However, after mutual adjustment for these factors, the difference in grip strength between settings remained significant. The Barthel score was the characteristic most strongly associated with grip strength. Conclusions: older people in rehabilitation and care home settings had lower grip strength than reported for those living at home. Furthermore grip strength varied widely between healthcare settings independent of known major influences. Further research is required to ascertain whether grip strength may help identify people at risk of adverse health outcomes within these settings.

Journal ArticleDOI
05 Jul 2014-Age
TL;DR: Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions.
Abstract: Cross-sectional studies show that older people with better cognition tend to walk faster. Whether this association reflects an influence of fluid cognition upon walking speed, vice versa, a bidirectional relationship or the effect of common causes is unclear. We used linear mixed effects models to examine the dynamic relationship between usual walking speed and fluid cognition, as measured by executive function, verbal memory and processing speed, in 2,654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relationship between walking speed and fluid cognition. After adjusting for age and sex, better performance on executive function, memory and processing speed was associated with less yearly decline in walking speed over the 6-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; and less yearly decline in each cognitive domain was associated with less yearly decline in walking speed. Effect sizes were small. After further adjustment for other covariates, effect sizes were attenuated but most remained statistically significant. We found some evidence that walking speed and the fluid cognitive domains of executive function and processing speed may change in parallel with increasing age. Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions.