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Showing papers by "Cyrus Cooper published in 2009"


Journal ArticleDOI
TL;DR: Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

1,710 citations


Journal ArticleDOI
TL;DR: Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined, and the design and implementation of control programs directed at this major health problem must be given.
Abstract: Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined. Noninvasive bone mineral measurements can be used to define a state of heightened fracture risk (osteopenia), or the ultimate clinical manifestation of fracture can be assessed (established osteoporosis). If bone mineral measurements more than 2 standard deviations below the mean of young normal women represent osteopenia, then 45% of white women aged 50 years and over have the condition at one or more sites in the hip, spine, or forearm on the basis of population-based data from Rochester, Minnesota. A smaller proportion is affected at each specific skeletal site: 32% have bone mineral values this low in the lumbar spine, 29% in either of two regions in the proximal femur, and 26% in the midradius. Although this overall estimate is substantial, some other serious chronic diseases are almost as common. More importantly, low bone mass is associated with adverse health outcomes, especially fractures. The lifetime risk of any fracture of the hip, spine, or distal forearm is almost 40% in white women and 13% in white men from age 50 years onward. If the enormous costs associated with these fractures are to be reduced, increased attention must be given to the design and implementation of control programs directed at this major health problem.

1,325 citations


Journal ArticleDOI
TL;DR: Observations show that patients are at increased risk for premature death for many years after a fragility-related hip fracture and highlight the need to identify those patients who are candidates for interventions to reduce their risk.
Abstract: This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlighting the need for interventions to reduce this risk.Patients experiencing hip fracture after low-impact trauma are at considerable risk for subsequent osteoporotic fractures and premature death. We conducted a systematic review of the literature to identify all studies that reported unadjusted and excess mortality rates for hip fracture. Although a lack of consistent study design precluded any formal meta-analysis or pooled analysis of the data, we have shown that hip fracture is associated with excess mortality (over and above mortality rates in nonhip fracture/community control populations) during the first year after fracture ranging from 8.4% to 36%. In the identified studies, individuals experienced an increased relative risk for mortality following hip fracture that was at least double that for the age-matched control population, became less pronounced with advancing age, was higher among men than women regardless of age, was highest in the days and weeks following the index fracture, and remained elevated for months and perhaps even years following the index fracture. These observations show that patients are at increased risk for premature death for many years after a fragility-related hip fracture and highlight the need to identify those patients who are candidates for interventions to reduce their risk.

878 citations


Journal ArticleDOI
Cecilia M. Lindgren1, Iris M. Heid2, Joshua C. Randall1, Claudia Lamina3  +152 moreInstitutions (36)
TL;DR: By focusing on anthropometric measures of central obesity and fat distribution, a meta-analysis of 16 genome-wide association studies informative for adult waist circumference and waist–hip ratio identified three loci implicated in the regulation of human adiposity.
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

648 citations


Cecilia M. Lindgren, Iris M. Heid, Joshua C. Randall, Claudia Lamina, Valgerdur Steinthorsdottir, Lu Qi, Elizabeth K. Speliotes, Gudmar Thorleifsson, Cristen J. Willer, Blanca M. Herrera, Anne U. Jackson, Noha Lim, Paul Scheet, Nicole Soranzo, Najaf Amin, Yurii S. Aulchenko, John C. Chambers, Alexander W. Drong, Jian'an Luan, Helen N. Lyon, Fernando Rivadeneira, Serena Sanna, Nicholas J. Timpson, M. Carola Zillikens, Jing Hua Zhao, Peter Almgren, Stefania Bandinelli, Amanda J. Bennett, Richard N. Bergman, Lori L. Bonnycastle, Suzannah Bumpstead, Stephen J. Chanock, Lynn Cherkas, Peter S. Chines, Lachlan J. M. Coin, Cyrus Cooper, Gabriel Crawford, Angela Doering, Anna F. Dominiczak, Alex S. F. Doney, Shah Ebrahim, Paul Elliott, Michael R. Erdos, Karol Estrada, Luigi Ferrucci, Guido Fischer, Nita G. Forouhi, Christian Gieger, Harald Grallert, Christopher J. Groves, Scott M. Grundy, Candace Guiducci, David Hadley, Anders Hamsten, Aki S. Havulinna, Albert Hofman, Rolf Holle, John W. Holloway, Thomas Illig, Bo Isomaa, Leonie C. Jacobs, Karen A. Jameson, Pekka Jousilahti, Fredrik Karpe, Johanna Kuusisto, Jaana Laitinen, G. Mark Lathrop, Debbie A Lawlor, Massimo Mangino, Wendy L. McArdle, Thomas Meitinger, Mario A. Morken, Andrew P. Morris, Patricia B. Munroe, Narisu Narisu, Anna Nordström, Peter Nordström, Ben A. Oostra, Colin N. A. Palmer, Felicity Payne, John F. Peden, Inga Prokopenko, Frida Renström, Aimo Ruokonen, Veikko Salomaa, Manjinder S. Sandhu, Laura J. Scott, Angelo Scuteri, Kaisa Silander, Kijoung Song, Xin Yuan, Heather M. Stringham, Amy J. Swift, Tiinamaija Tuomi, Manuela Uda, Peter Vollenweider, Gérard Waeber, Chris Wallace, G. Bragi Walters, Michael N. Weedon, Jacqueline C.M. Witteman, Cuilin Zhang, Weihua Zhang, Mark J. Caulfield, Francis S. Collins, George Davey Smith, Ian N.M. Day, Paul W. Franks, Andrew T. Hattersley, Frank B. Hu, Marjo-Riitta Järvelin, Augustine Kong, Jaspal S. Kooner, Markku Laakso, Edward G. Lakatta, Vincent Mooser, Andrew D. Morris, Leena Peltonen, Nilesh J. Samani, Tim D. Spector, David P. Strachan, Toshiko Tanaka, Jaakko Tuomilehto, André G. Uitterlinden, Cornelia M. van Duijn, Nicholas J. Wareham, Dawn M. Waterworth, Michael Boehnke, Panos Deloukas, Leif Groop, David J. Hunter, Unnur Thorsteinsdottir, David Schlessinger, H.-Erich Wichmann, Timothy M. Frayling, Gonçalo R. Abecasis, Joel N. Hirschhorn, Ruth J. F. Loos, Kari Stefansson, Karen L. Mohlke, Inês Barroso 
01 Jun 2009
TL;DR: Vandervell Foundation and Wellcome Trust (068545/Z/02, GR072960 as discussed by the authors, GR076113, GR069224, GR086596/Z /08/Z)
Abstract: Vandervell Foundation and Wellcome Trust (068545/Z/02, GR072960, GR076113, GR069224, 086596/Z/08/Z)

476 citations


Journal ArticleDOI
TL;DR: It is concluded that infant growth and physical activity in childhood are important determinants of peak bone mass in women and that physical activity was the major lifestyle determinant of BMD after allowing for body build.
Abstract: Peak bone mass is an important determinant of the risk of osteoporotic fracture, and preventive strategies against osteoporosis require a clear understanding of the factors influencing bone gain in early life. We report a longitudinal study aiming to identify the relationships between childhood growth, lifestyle, and peak bone mass in women. One hundred and fifty-three women born in a British city during 1968-1969 were traced and studied in 1990. Data on their growth in childhood was obtained from linked birth and school health records; current bone mineral measurements were made by dual X-ray absorptiometry. There were statistically significant associations between weight at 1 year and BMC (but not BMD) at the lumbar spine (r = 0.32, p < 0.01) and femoral neck (r = 0.26, p < 0.01). These remained significant after adjusting for current weight. There were also strong relationships between childhood height measurements and adult BMC at the two skeletal sites. Physical activity was the major lifestyle determinant of BMD after allowing for body build. We conclude that infant growth and physical activity in childhood are important determinants of peak bone mass in women. Growth primarily determines the size of the skeletal envelope, and its trajectory is established by age 1 year. Activity, in contrast, modulates the mineral density within the skeletal envelope and may contribute to the consolidation of bone following the end of linear growth.

409 citations


Journal ArticleDOI
TL;DR: The National Osteoporosis Guideline Group (NOGG), in collaboration with many Societies in the UK, have updated the original guidelines based on the development of new techniques for measuring bone mineral density and improved methods of assessing fracture risk.

377 citations


Journal ArticleDOI
TL;DR: There was a very small mean decrease in prudent diet score in pregnancy and a verySmall mean increase in high-energy diet score on average in late pregnancy, indicating little overall change in dietary patterns in pregnancy.
Abstract: Principal component analysis (PCA) is a popular method of dietary patterns analysis, but our understanding of its use to describe changes in dietary patterns over time is limited. Using a FFQ, we assessed the diets of 12,572 nonpregnant women aged 20-34 y from Southampton, UK, of whom 2270 and 2649 became pregnant and provided complete dietary data in early and late pregnancy, respectively. Intakes of white bread, breakfast cereals, cakes and biscuits, processed meat, crisps, fruit and fruit juices, sweet spreads, confectionery, hot chocolate drinks, puddings, cream, milk, cheese, full-fat spread, cooking fats and salad oils, red meat, and soft drinks increased in pregnancy. Intakes of rice and pasta, liver and kidney, vegetables, nuts, diet cola, tea and coffee, boiled potatoes, and crackers decreased in pregnancy. PCA at each time point produced 2 consistent dietary patterns, labeled prudent and high-energy. At each time point in pregnancy, and for both the prudent and high-energy patterns, we derived 2 dietary pattern scores for each woman: a natural score, based on the pattern defined at that time point, and an applied score, based on the pattern defined before pregnancy. Applied scores are preferred to natural scores to characterize changes in dietary patterns over time because the scale of measurement remains constant. Using applied scores, there was a very small mean decrease in prudent diet score in pregnancy and a very small mean increase in high-energy diet score in late pregnancy, indicating little overall change in dietary patterns in pregnancy.

311 citations


Journal ArticleDOI
TL;DR: The Southampton Women's Survey is a longitudinal study of women in Southampton, UK, characterised when they were not pregnant and again during pregnancy as mentioned in this paper, and the analyses are based on 1490 women who delivered between 1998 and 2003 and who provided information before pregnancy and at 11 and 34 weeks' gestation.
Abstract: A woman's life style choices before and during pregnancy have important implications for her unborn child, but information on behaviour can be unreliable when data are collected retrospectively. In particular there are no large longitudinal datasets that include information collected prospectively before pregnancy to allow accurate description of changes in behaviour into pregnancy. The Southampton Women's Survey is a longitudinal study of women in Southampton, UK, characterised when they were not pregnant and again during pregnancy. The objective of the analyses presented here is to describe the degree to which women comply with diet and life style recommendations before and during pregnancy, and changes between these time points. The analyses are based on 1490 women who delivered between 1998 and 2003 and who provided information before pregnancy and at 11 and 34 weeks' gestation. At each time point a trained research nurse ascertained smoking status and assessed food and drink consumption using a food frequency questionnaire. We derived the proportions of women who complied with recommendations not to smoke, to eat five portions of fruit and vegetables per day and to drink no more than four units of alcohol per week and 300 mg of caffeine per day. There was a notable reduction in smoking when women became pregnant: before pregnancy 27% of women smoked, whereas in early pregnancy 15% smoked. Similarly there were significant reductions in alcohol consumption and intake of caffeinated drinks: before pregnancy 54% of women drank more than four units of alcohol per week and 39% had estimated intakes of caffeine in drinks of >300 mg per day, whereas comparable figures for early pregnancy were 10% and 16% respectively. However, there was little change in fruit and vegetable intake; the percentages of women who did not achieve the recommendation to eat at least five portions of fruit and vegetables per week were 47% before pregnancy and 46% in early pregnancy. Younger women and those with fewer educational qualifications were less likely to comply with public health recommendations. Overall, 81% of women in early pregnancy complied with at least three of the recommendations. Although there is encouraging evidence of changed health behaviours in pregnancy, young women and those with few educational qualifications may particularly benefit from targeted health initiatives.

226 citations


Journal ArticleDOI
12 Feb 2009-BMJ
TL;DR: In this paper, the authors examined the extent to which women planning a pregnancy comply with recommendations for nutrition and lifestyle and found that only a small proportion of women plan a pregnancy follow the recommendations.
Abstract: Objective To examine the extent to which women planning a pregnancy comply with recommendations for nutrition and lifestyle. Design Prospective cohort study. Setting Southampton, United Kingdom. Participants 12 445 non-pregnant women aged 20-34 recruited to the Southampton Women’s Survey through general practices, 238 of whom became pregnant within three months of being interviewed. Main outcome measures Folic acid supplement intake, alcohol consumption, smoking, diet, and physical activity before pregnancy. Results The 238 women who became pregnant within three months of the interview were only marginally more likely to comply with recommendations for those planning a pregnancy than those who did not become pregnant in this period. Among those who became pregnant, 2.9% (95% confidence interval 1.2% to 6.0%) were taking 400 μg or more of folic acid supplements a day and drinking four or fewer units of alcohol a week, compared with 0.66% (0.52% to 0.82%) of those who did not become pregnant. 74% of those who became pregnant were non-smokers compared with 69% of those who did not become pregnant (P=0.08). Women in both groups were equally likely to consume five or more portions of fruit and vegetables a day (53% in each group, P=1.0), but only 57% of those who became pregnant had taken any strenuous exercise in the past three months compared with 64% in those who did not become pregnant (P=0.03). Conclusion Only a small proportion of women planning a pregnancy follow the recommendations for nutrition and lifestyle. Greater publicity for the recommendations is needed, but as many pregnancies are unplanned, improved nutrition and lifestyles of women of childbearing age is also required.

194 citations


Journal ArticleDOI
TL;DR: Data from a population‐based retrospective cohort study on Rochester women who were first diagnosed with one or more vertebral fractures in 1950–1979 are consistent with heterogeneity in the pathogenesis of different osteoporotic fractures.
Abstract: In a population-based retrospective cohort study, Rochester women aged 35-69 years who were first diagnosed with one or more vertebral fractures in 1950-1979 were followed for the development of a subsequent hip fracture. The 336 women with no history of hip fracture at the time of their vertebral fracture experienced 52 proximal femur fractures in 4788 person-years of follow-up. The standardized morbidity ratio (SMR) of observed to expected hip fractures was 1.8 (95% CI, 1.3-2.4) and was higher for intertrochanteric than cervical femoral fractures (SMR, 2.3 versus 1.3; P = 0.07). Hip fracture risk among women with symptomatic vertebral fractures was slightly less than in those with asymptomatic vertebral fractures (SMR, 1.8 versus 2.3; not significant), and younger women had no higher risk of a subsequent hip fracture than women who were > or = 60 years of age at the time of their vertebral fracture (SMR, 1.4 versus 1.8; not significant). Alternative explanations are possible, but these data are consistent with heterogeneity in the pathogenesis of different osteoporotic fractures. Language: en

Journal ArticleDOI
01 Oct 2009-Stroke
TL;DR: Stroke is associated with a 2.0-fold increase in the risk of hip/femur fracture, and the risk was highest among patients younger than 71 years, females, and those whose stroke was more recent.
Abstract: Background and Purpose— Stroke increases the risk of hip/femur fracture, as seen in several studies, although the time course of this increased risk remains unclear. Therefore, our purpose is to ev...

Journal ArticleDOI
TL;DR: The results are consistent with the SF-36 PF score being a valid measure of mobility disability in epidemiological studies, and might be a first step towards enabling simple comparisons of prevalence of disability between different studies of older people.
Abstract: Background Mobility disability is a major problem in older people. Numerous scales exist for the measurement of disability but often these do not permit comparisons between study groups. The physical functioning (PF) domain of the established and widely used Short Form-36 (SF-36) questionnaire asks about limitations on ten mobility activities.

Journal ArticleDOI
TL;DR: The data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis, but among elderly women, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur.
Abstract: High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified random sample of white women residing in Rochester, Minnesota After age adjustment, there was no association between overall caffeine consumption and bone mineral at five of the six sites In the femoral shaft, however, there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages When caffeine intake was categorized by source, no consistent influence of coffee, tea, or other caffeinated beverage consumption could be detected on bone mineral Caffeine intake was, however, positively associated with cigarette smoking and alcohol consumption After adjusting for age, caffeine consumption was not correlated with biochemical indices of bone turnover, circulating concentrations of estradiol and estrone, or other dietary and musculoskeletal variables These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis Among elderly women, however, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur

Journal ArticleDOI
TL;DR: Improvements in physical function following TKA for osteoarthritis are sustained beyond 5 years, and there seems no justification for withholding TKA from obese patients solely on the grounds of their body mass index.
Abstract: Objectives: To assess long-term outcome and predictors of prognosis following total knee arthroplasty (TKA) for osteoarthritis. Methods: We followed-up 325 patients from 3 English health districts approximately 6 years after TKA, along with 363 controls selected from the general population. Baseline data, collected by interview and examination, included age, sex, comorbidity, body mass index (BMI), functional status and preoperative radiographic severity of osteoarthritis. Functional status at follow-up was assessed by postal questionnaire. Predictors of change in physical function were analysed by linear regression. Results: Between baseline and follow-up, patients reported an improvement of 6 points in median Short Form 36 Health Survey (SF-36) physical function score, whereas in controls there was a deterioration of 14 points (p Conclusions: Improvements in physical function following TKA for osteoarthritis are sustained beyond 5 years. The benefits are apparent in patients who are obese as well as non-obese, and there seems no justification for withholding TKA from obese patients solely on the grounds of their body mass index.

Journal ArticleDOI
TL;DR: A dose–response effect on nonvertebral fractures was observed when comparing high with low ACE doses, and higher doses of ibandronate significantly reduced the risk of nonverTEbral fractures more effectively compared with lower doses.
Abstract: This analysis was conducted to assess the effect of high versus lower doses of ibandronate on nonvertebral fractures. The results were adjusted for clinical fracture, age, and bone density. The treatment effect was dose-dependent. Higher doses of ibandronate significantly reduced the risk of nonvertebral fractures more effectively compared with lower doses. The objective of this study was to assess the efficacy of different doses of ibandronate on nonvertebral fractures in a pooled analysis. Eight randomized trials of ibandronate were reviewed for inclusion. Alternative definitions of high versus low doses based on annual cumulative exposure (ACE) were explored. A time-to-event analysis was conducted using Kaplan–Meier methodology. Hazard ratios (HR) were derived using Cox regression and adjusted for covariates. Combining higher ACE doses of ≥ 10.8 mg (150 mg once monthly, 3 mg i.v. quarterly, and 2 mg i.v. every 2 months) versus ACE doses of 5.5 mg, from two trials, resulted in an HR 0.62 (95% CI 0.396–0.974, p = 0.038). There was a dose–response trend with increasing ACE doses (7.2–12 mg) versus ACE of 5.5 mg. A dose–response effect on nonvertebral fractures was observed when comparing high with low ACE doses. A significant reduction in nonvertebral fractures was noted when pooling data from trials using ACE doses of ≥ 10.8 mg versus ACE ≤ 7.2 mg; and with ACE ≥ 10.8 mg versus ACE of 5.5 mg (38% reduction). Higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmenopausal women.

Journal ArticleDOI
TL;DR: Dairy patterns consistent with current advice for healthy eating during pregnancy are associated with greater bone size and BMD in the offspring at 9 yr of age, after adjustment for sex, socioeconomic status, height, arm circumference, maternal smoking, and vitamin D status.
Abstract: Maternal nutrition is a potentially important determinant of intrauterine skeletal development. Previous studies have examined the effects of individual nutrients, but the pattern of food consumption may be of greater relevance. We therefore examined the relationship between maternal dietary pattern during pregnancy and bone mass of the offspring at 9 yr of age. We studied 198 pregnant women 17-43 yr of age and their offspring at 9 yr of age. Dietary pattern was assessed using principal component analysis from a validated food frequency questionnaire. The offspring underwent measurements of bone mass using DXA at 9 yr of age. A high prudent diet score was characterized by elevated intakes of fruit, vegetables, and wholemeal bread, rice, and pasta and low intakes of processed foods. Higher prudent diet score in late pregnancy was associated with greater (p < 0.001) whole body and lumbar spine BMC and areal BMD in the offspring, after adjustment for sex, socioeconomic status, height, arm circumference, maternal smoking, and vitamin D status. Associations with prudent diet score in early pregnancy were weaker and nonsignificant. We conclude that dietary patterns consistent with current advice for healthy eating during pregnancy are associated with greater bone size and BMD in the offspring at 9 yr of age.

Journal ArticleDOI
TL;DR: Data suggest that variations in both milk feeding and in the weaning diet are linked to differences in growth and development, and they have independent influences on body composition in early childhood.
Abstract: Context: Most studies of infant diet and later body composition focus on milk feeding; few consider the influence of variations in the weaning diet. Objective: Our objective was to examine how variations in milk feeding and the weaning diet relate to body composition at 4 yr. Study Population: A total of 536 children participating in a prospective birth cohort study. Design: Diet was assessed at 6 and 12 months of age. Compliance with weaning guidance was defined by the infant’s score for a principal component analysis-defined dietary pattern (infant guidelines) at 12 months. Infants with high infant guidelines scores had diets characterized by high consumption of fruit, vegetables, and home-prepared foods. Body composition was assessed at 4 yr by dual x-ray absorptiometry. Results: Longer duration of breastfeeding was associated with lower fat mass at 4 yr [4.5 kg, 95% confidence interval (CI) of 4.3–4.7 kg, in children breastfed for 12 months or more, compared with 5.0 (95% CI 4.7–5.3) kg in children ne...

Journal ArticleDOI
TL;DR: It is shown that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition.
Abstract: Summary Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients.

Journal ArticleDOI
TL;DR: ASM is associated with an increased risk of fracture when taken alone or in combination with bisphosphonates, and the frequency of coprescription of ASM and bisph phosphonates requires further investigation.
Abstract: Previous studies have found an association between acid suppressants and fracture risk. We assessed fracture risk in patients taking concomitant acid suppressant and bisphosphonates. Positive associations were observed for any hip and vertebral fracture. The effect size was modest; however, the significance lies in the widespread prescribing of acid suppressants. Previous studies have found that acid-suppressive medication (ASM) is associated with an increased risk of fracture. Bisphosphonates can cause upper gastrointestinal problems, and patients may be prescribed ASM to minimise these effects. A retrospective cohort study using the GPRD was conducted in patients aged 40 years and older starting proton pump inhibitors (PPI, N = 234,144), H2 receptor antagonists (H2RA, N = 166,798) or bisphosphonates (N = 67,309). Fracture risk in current versus past use of ASM and concomitant use of bisphosphonate plus ASM versus bisphosphonate alone was compared using time-dependent Cox regression. In the 6 months before initiating bisphosphonate therapy, 20.1% of patients received a PPI and 7.5% an H2RA. Current PPI use was associated with an increased risk of any (adjusted relative rate (ARR) 1.15, 95% CI 1.10–1.20), hip (ARR 1.22, 95% CI 1.10–1.37), and vertebral fracture (ARR 1.40, 95% CI 1.11–1.78); and concomitant bisphosphonates and PPIs with an increased risk of any (ARR 1.08, 95% CI 1.01–1.16) and hip fracture (ARR 1.24, 95% CI 1.08–1.42). ASM is associated with an increased risk of fracture when taken alone or in combination with bisphosphonates. Given the frequency of coprescription of ASM and bisphosphonates, this issue requires further investigation.

Journal ArticleDOI
TL;DR: To assess the relationship between depression scores and diabetes, glucose and insulin in a cross‐sectional population‐based study, a cross-sectional population-based study is conducted.
Abstract: Aims: to assess the relationship between depression scores and diabetes, glucose and insulin in a cross-sectional populationbased study. Methods: one thousand, five hundred and seventy-nine men and 1418 women from the Hertfordshire Cohort Study were assessed for diabetes. Plasma glucose and insulin concentrations were measured at 0, 30and 120 min during a standard 75-goral glucose tolerance test. Depressive and anxiety symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). Results: overall, 431 (14.6%)were diagnosed with diabetes [232 men (14.9%) and 199 women (14.3%)]. One hundred and eight (47%) men and 74 (37%) women had known diabetes. The remainder were previously undiagnosed. Fifty-nine (3.7%) men and 65 (4.6%) women had possible depression (HAD-D scores 8–10) and 17 (1.1%) men and 20 (1.4%) women had probable depression (HAD-D scores ‡ 11). Probable depression was associatedwith an adjusted odds ratio for diabetes of 3.89 [95% confidence interval (CI) 1.28–11.88] in men and 1.51 (95% CI 0.47–4.84) in women. In men without previously diagnosed diabetes, fasting insulin (P = 0.035), 2-h glucose concentrations (P = 0.028) and insulin resistance (P = 0.032)were significantly associated with HAD-D scores. With the exception of 2-h glucose concentrations (P = 0.034), the associations were not significant in women. Conclusions: these data support the hypothesis that depression may increase the risk for diabetes. The relationship between depression score and metabolic variables extends across thewhole population and is not confined to thosewith either diagnosed depression or diabetes. This relationship should lead clinicians to consider screening for diabetes in those with depression and vice versa.

Journal ArticleDOI
TL;DR: GLOW will provide contemporary information on patterns of management of fracture risk in older women over a 5-year period and provide insights into the distribution of risk among older women on an international basis.
Abstract: Summary The Global Longitudinal study of Osteoporosis in Women (GLOW) is a prospective cohort study involving 723 physicians and 60,393 women subjects ≥55 years. The data will provide insights into the management of fracture risk in older women over 5 years, patient experience with prevention and treatment, and distribution of risk among older women on an international basis.

Journal ArticleDOI
TL;DR: The use of conventional, but not atypical antipsychotics, seems to be associated with an increased risk of hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotic drugs.
Abstract: Summary This case–control study showed that current use of conventional antipsychotics, but not atypical antipsychotics, seems to be associated with an increased risk of a hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. Furthermore, no evidence for a dose effect was found.

Journal ArticleDOI
TL;DR: Children whose diet in infancy was characterised by high consumption of fruit, vegetables and home-prepared foods ('infant guidelines' dietary pattern) had higher full-scale and verbal IQ and better memory performance at age 4 years, suggesting that dietary patterns in early life may have some effect on cognitive development.
Abstract: Background: trials in developing countries suggest that improving young children's diet may benefit cognitive development. Whether dietary composition influences young children's cognition in developed countries is unclear. Although many studies have examined the relation between type of milk received in infancy and subsequent cognition, there has been no investigation of the possible effect of variations in the weaning diet. Methods: we studied 241 children aged 4 years, whose diet had been assessed at age 6 and 12 months. We measured IQ with the Wechsler Pre-School and Primary Scale of Intelligence, visual attention, visuomotor precision, sentence repetition and verbal fluency with the Developmental Neuropsychological Assessment (NEPSY), and visual form-constancy with the Test of Visual Perceptual Skills. Results: in sex-adjusted analyses, children whose diet in infancy was characterised by high consumption of fruit, vegetables and home-prepared foods ('infant guidelines' dietary pattern) had higher full-scale and verbal IQ and better memory performance at age 4 years. Further adjustment for maternal education, intelligence, social class, quality of the home environment and other potential confounding factors attenuated these associations but the relations between higher 'infant guidelines' diet score and full-scale and verbal IQ remained significant. For a standard deviation increase in 'infant guidelines' diet score at 6 or 12 months full-scale IQ rose by .18 (95% CI .04 to .31) of a standard deviation. For a standard deviation increase in 'infant guidelines' diet score at 6 months verbal IQ rose by .14 (.01 to .27) of a standard deviation. There were no associations between dietary patterns in infancy and 4-year performance on the other tests. Conclusions: these findings suggest that dietary patterns in early life may have some effect on cognitive development. It is also possible that they reflect the influence of unmeasured confounding factors

Journal ArticleDOI
TL;DR: The data confirm the impression from single‐center studies that vertebral height ratios vary between populations and suggest that reference values for vertebra height ratios should be derived separately for males and females within individual populations whenever possible.
Abstract: Vertebral height ratios are used to define vertebral deformity in clinical and epidemiologic studies of vertebral osteoporosis. However, few data have been obtained on the variation in these ratios in different populations using standard methods. We examined vertebral morphometric measurements obtained in a population survey from three centers: Malmo (Sweden), Montceau-les-Mines (France), and Graz (Austria), to study the influence of sex and the population center on vertebral height ratios. Radiographs were obtained according to a standardized protocol, and morphometric measurements, anterior height Ha, central height Hc, and posterior height Hp, made in Berlin. The height ratios anterior, Ha/Hp, central, Hc/Hp, posterior I, Hp/Hp', and posterior II, Hp/Hp" (Hp' = posterior height of vertebrae above, Hp" = posterior height of vertebrae below) were calculated for each vertebra from T4 to L4. The mean and standard deviation of these ratios for each sex and each center were derived using a statistical trimming procedure to normalize the distribution. Threshold values for defining grade 1 and grade 2 deformities, wedge, biconcavity, and compression, were calculated using these parameters. Anterior and central vertebral height ratios were smaller in males than females (p < 0.01). There were significant differences between the three centers (p < 0.01) both in the trimmed mean values for anterior and central vertebral height ratios and in the thresholds derived using standard criteria for defining wedge and biconcavity deformity. The data confirm the impression from single-center studies that vertebral height ratios vary between populations and suggest that reference values for vertebral height ratios should be derived separately for males and females within individual populations whenever possible.

Journal ArticleDOI
TL;DR: Environmental, social, historical and psychological factors known to be associated with food choice were explored and provide a starting point for taking forward the design of an intervention to improve the diets of young women.
Abstract: Women of lower educational attainment are more likely to eat unhealthy diets than women of higher educational attainment. To identify influences on the food choices of women with lower educational attainment, 11 focus groups (eight with women of lower, and three with women of higher educational attainment) were held. Using a semi-structured discussion guide, environmental, social, historical and psychological factors known to be associated with food choice were explored. Audio recordings were transcribed verbatim and thematically analysed. Compared to women of higher educational attainment, women of lower educational attainment had less control over their families' food choices, less support for attempts to eat healthily, fewer opportunities to observe and learn good food-related practices, more negative affect, more perceived environmental constraints and more ambiguous beliefs about the consequences of eating a nutritious diet. These findings provide a starting point for taking forward the design of an intervention to improve the diets of young women.

Journal ArticleDOI
TL;DR: Large variations in food consumption and nutrient intake amongst older adults that are likely to have implications for future health are described.
Abstract: Background: dietary patterns analysis takes account of the combined effects of foods and may be a more meaningful way of assessing dietary exposure than considering individual nutrients. Little is known about the dietary patterns of older adults in the UK. Objective: to describe the dietary patterns of a population of community-dwelling older men and women and to examine factors associated with compliance with these patterns. Setting and Participants: 3,217 men and women aged 59–73 years who were participants in the Hertfordshire Cohort Study. Methods: diet was assessed using an administered food frequency questionnaire; dietary patterns were identified using principal component analysis. Results: two dietary patterns were identified. The first was characterised by high consumption of fruit, vegetables, oily fish and wholemeal cereals (‘prudent’ pattern); the second was characterised by high consumption of vegetables, processed and red meat, fish and puddings (‘traditional’ pattern). High ‘prudent’ diet scores were more common in women, in men and women in non-manual classes and in non-smokers (all P Conclusions: we have described large variations in food consumption and nutrient intake amongst older adults that are likely to have implications for future health. The specific socio-demographic correlates of the dietary patterns provide insights into the contexts within which good and poor diets exist, and may help in the identification of opportunities for dietary intervention.

Book ChapterDOI
TL;DR: The optimisation of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.
Abstract: Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterised in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content, but not volumetric bone density, than girls. Furthermore, there is a dissociation between the peak velocities for height gain and bone mineral accrual in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the hypothalamic-pituitary-adrenal (HPA) and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axes. Maternal smoking, diet (particularly vitamin D deficiency) and physical activity also appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth, are directly linked to the later risk of hip fracture. The optimisation of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

Journal ArticleDOI
TL;DR: Hormonal and reproductive factors affect the risk of hip and knee replacement, more so for the knee than the hip.
Abstract: Objectives: To examine the effect of reproductive history and use of hormonal therapies on the risk of hip and knee joint replacement for osteoarthritis. Methods: Prospective study of 1.3 million women aged on average 56 years at recruitment and followed-up through linkage to routinely collected hospital admission records. The adjusted relative risk of hip and knee replacement for osteoarthritis was examined in relation to parity, age at menarche, menopausal status, age at menopause, and use of hormonal therapies. Results: Over a mean of 6.1 person-years of follow-up 12,124 women had a hip replacement and 9,977 a knee replacement. The risk of joint replacement increased with increasing parity and the effect was greater for the knee than the hip: increase in relative risk of 2% (95%CI 1-4%) per birth for hip replacement and 8% (95%CI 6-10%) for knee replacement. An early age at menarche slightly increased the risk of both hip and knee replacement (relative risk for menarche iU11yrs versus 12yrs 1.09(95%CI 1.03-1.16) and 1.15(95%CI 1.08-1.22) respectively). Menopausal status and age at menopause were not clearly associated with risk. Current use of post-menopausal hormone therapy was associated with a significant increase in the incidence of both hip and knee replacement (RR=1.38(95%CI 1.30-1.46) and RR=1.58(95%CI 1.48-1.69) respectively) while previous use of oral contraceptives was not (RR=1.02(95%CI 0.98-1.06) and RR=1.00(95%CI 0.96-1.04) for hip and knee respectively). Conclusions: Hormonal and reproductive factors affect the risk of hip and knee replacement, more so for the knee than the hip. The reasons for this are unclear.

Journal ArticleDOI
TL;DR: Overall, this maternal questionnaire had reasonable validity and internal consistency for assessing potential correlates of physical activity in young children and could be a useful tool for future research in this area.
Abstract: Valid measures of physical activity correlates in preschool children are lacking. This study aimed to assess the validity, factor structure and internal consistency of a maternal questionnaire on potential correlates of four-year-old children's physical activity. The questionnaire was designed to measure the following constructs: child personal factors; parental support and self-efficacy for providing support; parental rules and restrictions; maternal attitudes and perceptions; maternal behaviour; barriers to physical activity; and the home and local environments. Two separate studies were conducted. Study I included 24 mothers of four-year-old children who completed the questionnaire then participated in a telephone interview covering similar items to the questionnaire. To assess validity, the agreement between interview and questionnaire responses was assessed using Cohen's kappa and percentage agreement. Study II involved 398 mothers of four-year-old children participating in the Southampton Women's Survey. In this study, principal components analysis was used to explore the factor structure of the questionnaire to aid future analyses with these data. The internal consistency of the factors identified was assessed using Cronbach's alpha. Kappa scores showed 30% of items to have moderate agreement or above, 23% to have fair agreement and 47% to have slight or poor agreement. However, 89% of items had fair agreement as assessed by percentage agreement (≥ 66%). Limited variation in responses to variables is likely to have contributed to some of the low kappa values. Six questions had a low kappa and low percentage agreement (defined as poor validity); these included questions from the child personal factors, maternal self-efficacy, rules and restrictions, and local environment domains. The principal components analysis identified eleven factors and found several variables to stand alone. Eight of the composite factors identified had acceptable internal consistency (α ≥ 0.60) and three fell just short of achieving this (0.60 > α > 0.50). Overall, this maternal questionnaire had reasonable validity and internal consistency for assessing potential correlates of physical activity in young children. With minor revision, this could be a useful tool for future research in this area. This, in turn, will aid the development of interventions to promote physical activity in this age group.