Showing papers by "Cyrus Cooper published in 2010"

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

Abstract: Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

Using natural experiments to evaluate population health interventions

Abstract: Craig P, Cooper C, Gunnell D, Haw S, Lawson K, Macintyre S, Ogilvie D, Petticrew M, Reeves B, Sutton M, Thompson S

Genome-wide association study identifies five loci associated with lung function.

Abstract: Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Osteoporosis: impact on health and economics

Abstract: Osteoporosis is a major public health problem through associated fragility fractures. The most common sites of fracture are the hip, spine and wrist, and these have an enormous health and economic impact. All fractures result in some degree of morbidity, but fractures at the hip are associated with the worst outcomes. The worldwide direct and indirect annual costs of hip fracture in 1990 were estimated at US$34.8 billion, and are expected to increase substantially over the next 50 years. Fracture incidence varies between populations, and is set to increase over coming decades as the global population becomes more elderly. This effect will be particularly marked in the developing world, which is additionally assuming more-westernized lifestyles that predispose to increased fracture risk. Strategies to target those at high risk of fracture have been developed, but preventative measures at the public health level are also urgently needed to reduce the burden of this devastating disease.

Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe

Abstract: Objectives: To identify participants’ characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. Design: Individual patient data analysis using pooled data from randomised trials. Data sources: Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Study selection: Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants. Data synthesis: Logistic regression analysis was used to identify significant interaction terms, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use. Results: Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 μg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 μg or 20 μg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy. Conclusion: This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.

Low maternal vitamin D status and fetal bone development: cohort study.

Abstract: Recent findings suggest that maternal vitamin D insufficiency during pregnancy has consequences for the offspring's bone health in later life. To investigate whether maternal vitamin D insufficiency affects fetal femur growth in ways similar to those seen in childhood rickets and study the timing during gestation of any effect of maternal vitamin D status, we studied 424 pregnant women within a prospective longitudinal study of maternal nutrition and lifestyle before and during pregnancy (Southampton Women's Survey). Using high-resolution 3D ultrasound, we measured fetal femur length and distal metaphyseal cross-sectional area, together with the ratio of femoral metaphyseal cross-sectional area to femur length (femoral splaying index). Lower maternal 25-hydroxyvitamin vitamin D concentration was not related to fetal femur length but was associated with greater femoral metaphyseal cross-sectional area and a higher femoral splaying index at 19 weeks' gestation [r = -0.16, 95% confidence interval (CI) -0.25 to -0.06 and r = -0.17, 95% CI -0.26 to -0.07, respectively] and at 34 weeks' gestation (r = -0.10, 95% CI -0.20 to 0.00 and r = -0.11, 95% CI -0.21 to -0.01, respectively). Three groups of women were identified with 25-hydroxyvitamin vitamin D concentrations that were sufficient/borderline (> 50 nmol/L, 63.4%), insufficient (25 to 50 nmol/L, 30.7%), and deficient (< or = 25 nmol/L, 5.9%). Across these groups, the geometric mean femoral splaying indices at 19 weeks' gestation increased from 0.074 (sufficient/borderline) to 0.078 (insufficient) and 0.084 (deficient). Our observations suggest that maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks' gestation. This suggests that measures to improve maternal vitamin D status should be instituted in early pregnancy.

Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans

Abstract: OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS-The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS-Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. Diabetes 59:1266-1275, 2010

Prevalence and correlates of frailty among community-dwelling older men and women: findings from the Hertfordshire Cohort Study

Abstract: Background: frailty, a multi-dimensional geriatric syndrome, confers a high risk for falls, disability, hospitalisation and mortality. The prevalence and correlates of frailty in the UK are unknown. Methods: frailty, defined by Fried, was examined among community-dwelling young-old (64–74 years) men (n = 320) and women (n = 318) who participated in the Hertfordshire Cohort Study, UK. Results: the prevalence of frailty was 8.5% among women and 4.1% among men (P = 0.02). Among men, older age (P = 0.009), younger age of leaving education (P = 0.05), not owning/mortgaging one's home (odds ratio [OR] for frailty 3.45 [95% confidence interval {CI} 1.01–11.81], P = 0.05, in comparison with owner/mortgage occupiers) and reduced car availability (OR for frailty 3.57 per unit decrease in number of cars available [95% CI 1.32, 10.0], P = 0.01) were associated with increased odds of frailty. Among women, not owning/mortgaging one's home (P = 0.02) was associated with frailty. With the exception of car availability among men (P = 0.03), all associations were non-significant (P > 0.05) after adjustment for co-morbidity. Conclusions: frailty is not uncommon even among community-dwelling young-old men and women in the UK. There are social inequalities in frailty which appear to be mediated by co-morbidity.

Genetic variation in the SMAD3 gene is associated with hip and knee osteoarthritis.

Abstract: Objective Smad3 (or, MADH3) is a key intracellular messenger in the transforming growth factor β signaling pathway. In mice, Smad3 deficiency accelerates growth plate chondrocyte maturation and leads to an osteoarthritis (OA)–like disease. We undertook this study to investigate the role of genetic variation in SMAD3 in the risk of large-joint OA in humans. Methods Ten tag single-nucleotide polymorphisms (SNPs) in the SMAD3 gene region were tested in a discovery set: 313 patients who had undergone total knee replacement, 214 patients who had undergone total hip replacement, and 520 controls from the UK. The SNP associated with both hip and knee OA was subsequently genotyped in 1,221 controls and 1,074 cases from 2 cohorts of patients with hip OA and 2,537 controls and 1,575 cases from 4 cohorts of patients with knee OA. Results A SNP (rs12901499) mapping to intron 1 of SMAD3 was associated with both knee and hip OA (P < 0.0022 and P < 0.021, respectively) in the discovery set. In all study cohorts, the major allele (G) was increased among OA patients relative to controls. A meta-analysis for knee OA yielded an odds ratio (OR) of 1.22 (95% confidence interval [95% CI] 1.12–1.34), P < 7.5 × 10−6. For hip OA, the OR was 1.22 (95% CI 1.09–1.36), P < 4.0 × 10–4. No evidence for heterogeneity was found (I2 = 0%). Conclusion Our data indicate that genetic variation in the SMAD3 gene is involved in the risk of both hip OA and knee OA in European populations, confirming the results from animal models on the potential importance of this molecule in the pathogenesis of OA.

Patient-reported outcomes one year after primary hip replacement in a European Collaborative Cohort.

Abstract: Objective: to identify whether patients have symptomatic improvement 12 months following total hip replacement (THR) surgery. Methods: the European Collaborative Database of Cost and Practice Patterns of Total Hip Replacement study consists of 1,327 patients receiving primary THR for osteoarthritis (OA) across 20 European orthopedic centers. The primary outcome was the difference in Western Ontario and McMaster Universities OA Index (WOMAC) score between preoperative and 12-month postoperative measurements. To classify whether patients responded to THR at 12 months, we used return to normal, Outcome Measures in Rheumatology Clinical Trials (OMERACT)-OA Research Society International (OARSI) criteria, minimum important difference (MID), and minimum clinically important difference. Exposures were age, sex, obesity, employment, educational attainment, American Society of Anesthesiologists status, and radiographs. Results: on average, there was a large improvement in WOMAC scores 12 months after surgery, but whereas some patients improved, others got worse. The OMERACT-OARSI method classified 85.7% of patients as responders, MID 70.1%, and return to normal 64.1%. In general, each approach classified the same groups of patients as responding to THR. Based on total WOMAC score, patients who were younger, morbidly obese, employed, and better educated were more likely to respond to THR, but the effects were attenuated after adjustment for confounding, with only the effect of education remaining important. Conclusion: the overall average response to THR was good, but 14-36% of patients did not improve, or were worse, 12 months postsurgery. Although the OMERACT-OARSI criteria were originally designed for use in clinical drug trials, they performed well in classifying patient response 12 months post-THR. Further research is required to understand the determinants of patient outcomes following THR.

The epidemiology of osteonecrosis: findings from the GPRD and THIN databases in the UK

Abstract: Summary We conducted a case–control study to examine osteonecrosis (ON) incidence, patient characteristics, and selected potential risk factors using two health record databases in the UK. Statistically significant risk factors for ON included systemic corticosteroid use, hospitalization, referral or specialist visit, bone fracture, any cancer, osteoporosis, connective tissue disease, and osteoarthritis.

Ultrasound measurements of visceral and subcutaneous abdominal thickness to predict abdominal adiposity among older men and women.

Abstract: Accurate measures of visceral and abdominal subcutaneous fat are essential for investigating the pathophysiology of obesity. Classical anthropometric measures such as waist and hip circumference cannot distinguish between these two fat depots. Direct imaging methods such as computed tomography and magnetic resonance imaging (MRI) are restricted in large-scale studies due to practical and ethical issues. We aimed to establish whether ultrasound is a valid alternative method to MRI for the quantitative assessment of abdominal fat depots in older individuals. The study population comprised 74 white individuals (41 men and 33 women, aged 67-76 years) participating in the Hertfordshire Birth Cohort Physical Activity trial. Anthropometry included height, weight, waist and hip circumferences. Abdominal fat was measured by ultrasound in two compartments: visceral fat defined as the depth from the peritoneum to the lumbar spine; and subcutaneous fat defined as the depth from the skin to the abdominal muscles and compared to reference measures by MRI (10-mm single-slice image). Ultrasound measures were positively correlated with MRI measures of visceral and subcutaneous fat (visceral: r = 0.82 and r = 0.80 in men and women, respectively; subcutaneous: r = 0.63 and 0.68 in men and women, respectively). In multiple regression models, the addition of ultrasound measures significantly improved the prediction of visceral fat and subcutaneous fat in both men and women over and above the contribution of standard anthropometric variables. In conclusion, ultrasound is a valid method to estimate visceral fat in epidemiological studies of older men and women when MRI and computed tomography are not feasible.

Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis.

Abstract: Bisphosphonates are the leading drugs for the treatment of osteoporosis. In randomized controlled trials (RCTs), alendronate, risedronate, and zoledronate have shown to reduce the risk of vertebral, nonvertebral, and hip fractures, whereas RCTs with ibandronate show antifracture efficacy at vertebral sites. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted, and it is important to consider the strength of the evidence for causal relationships. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Case reports have suggested a relationship between oral bisphosphonates and esophageal cancer, but this has not been demonstrated in epidemiologic studies. A possible association between bisphosphonate use and osteonecrosis of the jaw (ONJ) has also been suggested. However, the risk of ONJ in patients with osteoporosis appears to be very low, with no evidence from prospective RCTs of a causal association. There are reports of occasional occurrence of subtrochanteric or diaphyseal fractures in osteoporotic patients, but an association with bisphosphonate therapy is not substantiated by epidemiologic studies or prospective RCTs.

The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial.

Abstract: Aims/hypothesis We sought to determine the effect of an aerobic exercise intervention on clustered metabolic risk and related outcomes in healthy older adults in a single-centre, explanatory randomised controlled trial.

Geographic variation in osteoporotic hip fracture incidence: the growing importance of asian influences in coming decades.

Abstract: Studies over the last few decades have demonstrated geographic variation in the incidence of hip fracture across continents and among different parts of the same region. This paper studies the epidemiology of hip fracture worldwide, with special emphasis on the geographic variation among Asian countries. Using the Pubmed database, keywords that were employed included hip fracture, incidence rate, geographic variation, osteoporosis, and epidemiology. Articles were chosen based on the basis of (1) focus: studies that were said to specifically focus on geographic variation in hip fracture from different continents with a focus on Asia; (2) language: studies that were in English; (3) methods: studies that used statistical tests to examine hip fracture incidence rates. The highest hip fracture rates are seen in Scandinavian countries and the US and the lowest in African countries. Fracture rates are intermediate in Asian populations. Among different ethnic populations, the highest fracture rates are seen in Caucasians and the lowest in blacks. There is also a north-south gradient, particularly in Europe, where more hip fractures occur in North Europe compared to the South.

Maternal predictors of neonatal bone size and geometry: the Southampton Women's Survey.

Abstract: Early growth is associated with later risk of osteoporosis and fractures. In this study, we aimed to evaluate the relationships between maternal lifestyle and body composition and neonatal bone size, geometry and density in the offspring. Participants were recruited from the Southampton Women’s Survey, a unique prospective cohort of 12,500 initially non-pregnant women aged 20–34 years, resident in Southampton, UK. These women were studied in detail before and during pregnancy, and the offspring underwent anthropometric and bone mineral assessment (using dual energy-X-ray absorptiometry) at birth. A total of 841 mother–baby pairs were studied (443 boys and 398 girls). The independent predictors of greater neonatal whole body bone area (BA) and bone mineral content included greater maternal birthweight, height, parity, triceps skinfold thickness and lower walking speed in late pregnancy. Maternal smoking was independently associated with lower neonatal bone mass. Neonatal BA adjusted for birth length (a measure of bone width) was predicted positively by maternal parity and late pregnancy triceps skinfold thickness and negatively by late pregnancy walking speed. These findings were similar in both genders. We have confirmed, in a large cohort, previous findings that maternal lifestyle and body build predict neonatal bone mineral; additionally, maternal parity and fat stores and walking speed in late pregnancy were associated with neonatal bone geometry. These findings may suggest novel public health strategies to reduce the burden of osteoporotic fracture in future generations.

Are pain and function better measures of outcome than revision rates after TKR in the younger patient

Abstract: Revision is the gold standard outcome measurement for survival analyses of orthopaedic implants but reliance on revision as an endpoint has been recently questioned. This study, that assesses long-term outcome in a specific group of patients who had undergone total knee replacement (TKR) for osteoarthritis, highlights the main problems facing modern survival analyses. Minimum 12-year survival and outcome data were reviewed for a series of sixty patients under the age of 60 years (mean age 55.4 years) who underwent total knee replacement (TKR) for osteoarthritis. The patients are a subgroup from a larger consecutive series of 1429 patients who underwent TKR between 1987 and 1993 at a single institution. Whilst the main study aim was to compare outcome of TKR using different endpoints, the outcome of TKR in this younger subpopulation could also be investigated. With revision as the primary endpoint the survival for TKR was 82.2% (95% CI 17.3). The mean OKS at follow-up (mean 15.7 years) was 30.9. However, many of the 82% of patients who did not undergo revision had a less than satisfactory outcome. 41% of these patients reported modest or severe pain (using the OKS) at final follow-up. A combined endpoint including revision, poor function and significant pain drastically reduced the survival rate for the operation. Survival based on revision alone provides an acceptable but inaccurate impression of outcome in younger TKR patients (under 60 years). A true representation of the success of TKR should include pain and function as endpoints.

Grip strength and cardiovascular drug use in older people: findings from the Hertfordshire Cohort Study

Abstract: Background: reduced grip strength is associated with adverse health consequences, and there is interest in identifying modifiable influences. Cardiovascular drugs are commonly used by older people, but their effect on muscle strength is unclear. Methods: we investigated associations between cardiovascular drug use and grip strength among 1,572 men and 1,415 women, aged 59–73, who participated in the Hertfordshire Cohort Study. Results: forty-five percent of participants were taking a cardiovascular drug. Furosemide was associated with average decreases in grip strength of 3.15 kg (95% confidence interval [CI] 0.90, 5.39, P Conclusions: use of some cardiovascular drugs is associated with reduced grip strength in older people. These findings have potential implications for the functional ability of older people treated with these drugs

Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database

Abstract: Summary In a retrospective cohort study using the General Practice Research Database (GPRD), there was a greater association of venous thromboembolism (VTE) in osteoporotic than in non-osteoporotic female patients. No greater association was shown in treated patients with strontium ranelate or alendronate compared to untreated osteoporotic female patients.

Involvement of different risk factors in clinically severe large joint osteoarthritis according to the presence of hand interphalangeal nodes.

Abstract: Objective To quantify the differences in risk factors influencing total hip replacement (THR) and total knee replacement (TKR) based on the presence versus absence of multiple interphalangeal nodes in 2 or more rays of the fingers of each hand in patients with large joint osteoarthritis (OA). Methods A group of 3,800 patients with large joint OA who underwent total joint replacement (1,201 of whom had the nodal phenotype) and 1,906 control subjects from 2 case–control studies and a population-based cohort in the UK were studied. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk of total joint replacement in association with age, sex, body mass index (BMI), height, and prevalence of the T allele in the GDF5 rs143383 polymorphism. ORs for total joint replacement were compared between cases of nodal OA and cases of non-nodal OA and between patients who underwent TKR and those who underwent THR. Results Age, sex, and BMI had significantly higher ORs for an association with total joint replacement in nodal OA cases than in non-nodal OA cases. The GDF5 polymorphism was significantly associated with THR in cases of nodal OA, but not in cases of non-nodal OA, and increased height was a risk factor for THR in non-nodal OA cases only. Female sex was a protective risk factor for TKR in non-nodal OA cases (OR 0.60, 95% CI 0.52–0.70) but was predisposing for TKR in the nodal form of OA (OR 1.83, 95% CI 1.49–2.26). The nodal phenotype was associated with a significantly higher risk of undergoing both THR and TKR (OR 1.46, 95% CI 1.09–1.94) and also a significantly higher risk of bilateral TKR (OR 1.70, 95% CI 1.37–2.11), but, paradoxically, was associated with a lower risk of bilateral THR (OR 0.72, 95% CI 0.56–0.91). Conclusion Nodal and non-nodal forms of large joint OA have significantly different risk factors and outcomes, indicating a different etiology for the 2 forms of OA. With regard to the likelihood of undergoing THR, this appears to be, at least in part, genetically determined.

Development of a 20-item food frequency questionnaire to assess a 'prudent' dietary pattern among young women in Southampton

Abstract: Objective: to develop a short food frequency questionnaire (FFQ) that can be used among young women in Southampton to assess compliance with a prudent dietary pattern characterized by high consumption of wholemeal bread, fruit and vegetables, and low consumption of sugar, white bread, and red and processed meat. Methods: diet was assessed using a 100-item interviewer-administered FFQ in 6129 non-pregnant women aged 20–34 years. In total, 94 of these women were re-interviewed 2 years later using the same FFQ. Subsequently, diet was assessed in 378 women attending SureStart Children's Centres in the Nutrition and Well-being Study (NWS) using a 20-item FFQ. The 20 foods included were those that characterized the prudent dietary pattern. Results: the 20-item prudent diet score was highly correlated with the full 100-item score (r=0.94) in the Southampton Women's Survey (SWS). Both scores were correlated with red blood cell folate (r=0.28 for the 100-item score and r=0.25 for the 20-item score). Among the women re-interviewed after 2 years, the change in prudent diet score was correlated with change in red cell folate for both the 20-item (rS=0.31) and 100-item scores (rS=0.32). In the NWS a strong association between the 20-item prudent diet score and educational attainment (r=0.41) was observed, similar to that seen in the SWS (r=0.47). Conclusions: the prudent diet pattern describes a robust axis of variation in diet. A 20-item FFQ based on the foods that characterize the prudent diet pattern has clear advantages in terms of time and resources, and is a helpful tool to characterize the diets of young women in Southampton

Reduced cortical bone density with normal trabecular bone density in girls with Turner syndrome

Abstract: This study of 22 girls with Turner syndrome (TS) demonstrates a reduction in bone mineral apparent density (BMAD) at the femoral neck along with a reduction in cortical bone density at the radius (with sparing of trabecular bone). These findings may account for the increased fracture risk noted in this population. Increased fracture risk is a feature of TS; however, the reasons for this are unclear. Little is known regarding cortical and trabecular bone mineral density (BMD) in TS. We have addressed this by measurement of volumetric bone mineral density (vBMD) using peripheral quantitative computed tomography (pQCT). We studied 22 females with TS and 21 females without TS; mean ages 12.7 and 12.9 years, respectively. Bone mass measurements were made by dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femur and pQCT of the radius. BMAD was calculated from DXA values. We utilized published reference data to generate Z-scores for both populations. The mean BMAD Z-score at the lumbar spine was not significantly different in individuals with TS compared to the controls. At the femoral neck, individuals with TS had a significantly lower BMAD Z-score compared to the controls (−1.32 vs. −0.14, p = 0.001). At the distal radius, total vBMD Z-score and trabecular vBMD Z-score were not significantly different between the TS group and controls. A significant reduction in cortical vBMD at the proximal radius was noted in the TS group however (−2.58 vs. −1.38, p = 0.02). There was also a trend towards reduced cortical thickness at this site in the TS group (Z-score −2.89 vs. −1.73, p = 0.08). TS is associated with reduced BMAD at the femoral neck; pQCT data suggests that cortical density is reduced with sparing of trabecular bone. This differential of cortical and trabecular BMD may predispose to fracture.