PubMed Health⌕ Search

Biomedical subjects

Cyrus Cooper

Publications and source records attributed to Cyrus Cooper.

At least 37 records · Page 2Linked to original sources
PubMed2006

Combined effects of dietary fat and birth weight on serum cholesterol concentrations: the Hertfordshire Cohort Study.

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

Aged↗
PubMed2006

Developmental origins of midlife grip strength: findings from a birth cohort study.

BACKGROUND: There is growing evidence that the prenatal environment has long-term effects on adult grip strength, but little is known about the effects of the postnatal environment. We tested whether prepubertal growth, pubertal growth, or the development of motor and cognitive capabilities was associated with midlife muscle strength independently of other determinants of grip strength. METHODS: Handgrip strength and body size were measured in a representative British sample of 1406 men and 1444 women 53 years old with prospective childhood data. Normal regression models were used to examine the effects of birth weight, postnatal height and weight gain before 7 years and between 7 and 15 years, motor milestones and cognitive ability on grip strength at age 53, taking account of lifetime social class, current physical activity, and health status. RESULTS: Birth weight and prepubertal height gain were associated with midlife grip strength, independently of later weight and height gain and other determinants. Pubertal growth was also independently associated with midlife grip strength; for men weight gain during puberty was beneficial, whereas for women it was height gain. Those participants with earlier infant motor development had better midlife grip strength, which was partly confounded by the growth trajectory. CONCLUSIONS: This study showed that components of prenatal, prepubertal, and pubertal growth have long-term effects on midlife grip strength. To the extent that these associations are modifiable, interventions in childhood that help to build muscle mass and strength, such as increased physical exercise, may have long-term beneficial effects on adult muscle strength and may help to prevent sarcopenia, disability, and frailty in later life.

Adolescent↗
PubMed2006

Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database.

BACKGROUND: Two recent case-control studies by Meier et al. and van Staa et al. used the UK General Practice Research Database (GPRD) to examine the association between the use of statins and the risk of fractures, with different results. The objective of the present study was to examine methodological explanations for the discrepant results. METHODS: We created two datasets, which mimicked the previous study designs: a 'selected population' (SP) case-control dataset, with fracture cases matched to controls nested within a selected cohort (Meier et al.), and an 'entire population' (EP) case-control dataset, with both cases and controls sampled from the total GPRD population (van Staa et al.). Cases and controls were matched by gender, age (year of birth or 5 year age bands), and general practice. RESULTS: The study included 131 855 fracture cases. The crude odds ratio (OR) for hip fracture in statin users was 0.37 (95% CI 0.27-0.52) in the SP and 0.54 (95% CI 0.39-0.74) in the EP dataset. This difference was reduced when matching by year of birth, rather than by 5 year age bands: crude ORs were 0.58 (95% CI 0.43-0.79) and 0.61 (95% CI 0.44-0.88), respectively. In the SP dataset, 37% of the cases could be matched by year of birth, while this was achieved for 99% in the 'EP' dataset. The exposure time-window, the selection of confounders, and exclusion of high-risk patients also influenced results. CONCLUSION: Residual confounding by a matching variable and different definitions of the exposure time window explained differences in results. In case-control studies of drug use and fracture risk, broad matching criteria for age should be avoided and the selection of the time-window for exposure should be carefully considered.

Aged↗
PubMed2006

Epidemiology of Paget's disease in Europe: the prevalence is decreasing.

UNLABELLED: This study estimated changes in the age- and sex-specific prevalence of Paget's disease of bone in six European towns over a 20-year period. Declines in prevalence were observed in this disorder, occurring among both men and women. INTRODUCTION: To estimate secular changes in the age-and sex-specific prevalence of Paget's disease of bone in Europe, we conducted a second radiographic survey using identical sampling and methods in six European towns where a baseline study was performed in 1978-1979. In addition to these towns, the survey was carried out in two Hungarian centers not included in the initial study. MATERIALS AND METHODS: In each center, a sample of abdominal radiographs of people >or=55 years of age was taken from stored films within the radiology department of the principal general hospital. Radiographs showing the entire pelvis, sacrum, femoral heads, and lumbar vertebrae were studied for the period of 2000-2001. The films were evaluated by a trained observer and a consultant radiologist. RESULTS: A total of 6935 radiographs (3512 women and 3423 men) were assessed in the eight towns. The overall age- and sex-standardized prevalence rate of Paget's disease was 0.3% with a male/female ratio of 1.5. Prevalence increased with age among men and women rising to 0.8% of men and 0.9% of women >/=85 years of age. The differences in prevalence rate among the European centers were relatively small, especially in women. There was a decline in rates between 1978/79 and 2000/01. CONCLUSIONS: These European data confirm the decrease in frequency of Paget's disease observed in Britain. These declines favor an environmental contribution to the causation of the disease that requires further research.

Age Factors↗
PubMed2006

Update on the epidemiology of Paget's disease of bone.

Paget's disease of bone (PDB) is characterized by rapid bone remodeling and the formation of bone that is structurally abnormal. Recent studies have confirmed that both genetic and environmental factors are important in its etiology. Epidemiological studies in Europe and North America have revealed that PDB shows an increasing frequency of occurrence with age and is more prevalent among men than women. There is marked geographic variation in the prevalence of PDB throughout western nations, with the highest rates reported during the 1970s in Britain. Recent studies of the secular trends in PDB suggest declining rates in both prevalence and severity at diagnosis. Thus, the overall age/sex standardized prevalence rate in Britain during the period 1993-1995 was found to be 2.5% among men and 1.6% among women > or = 55 years of age. Prevalence rates had fallen by approximately 50% in several of the centers studied, suggesting an environmental contribution to the etiology of this disorder. Similar findings have been reported from other European countries and New Zealand. Recent study of the incidence and clinical manifestations of PDB have emerged from large cohort studies in primary care record linkage resources, such as the General Practice Research Database. Over the period 1988-1999, the incidence rate of clinically diagnosed PDB was found to be 5 per 10,000 person-years among men and 3 per 10,000 person-years among women 75 years of age. The disorder was associated with an increased risk of back pain (RR, 2.1; 95% CI, 1.9-2.3); osteoarthritis (RR, 1.7; 95% CI, 1.5-1.9); and fracture (RR, 1.2; 95% CI, 1.0-1.5). Using life table methodology, the estimated proportion of patients dying within 5 years of follow-up was 32.7% among the cohort with PDB compared with 28.0% among control patients (p < 0.05).

Australia↗
PubMed2005

Review: developmental origins of osteoporotic fracture.

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 (BMC), 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 birth weight, 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 HPA and 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.

Adolescent↗
PubMed2005

A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate.

Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval>2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.

Administration, Oral↗
PubMed2005

Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study.

UNLABELLED: Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. INTRODUCTION: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. MATERIALS AND METHODS: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. RESULTS: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. CONCLUSIONS: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed2005

Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: the FAMOS study.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and an increased risk of fracture. Bone mineral density (BMD) is a highly heritable trait and a key determinant of osteoporotic fracture risk, but the genes responsible are incompletely defined. Here, we identified quantitative trait loci (QTL) for regulation of BMD by a genome wide scan involving 3691 individuals from 715 families, who were selected because of reduced BMD values at the lumbar spine (LS-BMD) or femoral neck (FN-BMD) in probands. Linkage analysis was conducted in the study group as a whole with correction for age, gender, weight and height. Further analyses were conducted for men and women separately to identify gender-specific QTL and for those under and over the age of 50 years to distinguish QTL for peak bone mass from those that influence bone mass in older people. No regions of suggestive or significant linkage were identified when data from all subjects were analyzed together. On subgroup analysis, however, we identified a significant QTL for FN-BMD on chromosome 10q21 (LOD score +4.42; men < or =50 years) and two suggestive QTL for LS-BMD on chromosomes 18p11 (LOD score +2.83; women >50 years) and 20q13 (LOD score +3.20; women < or =50 years). We identified five other QTL for BMD with LOD scores of greater than +2.20 on chromosomes 3q25, 4q25, 7p14, 16p13 and 16q23. This study provides evidence for gender-specific, site-specific and age-specific QTL, which regulate BMD in humans, and illustrates the importance of conducting subgroup analysis to detect these loci.

Bone Density↗
PubMed2005

Birth weight and weight at 1 year are independent determinants of bone mass in the seventh decade: the Hertfordshire cohort study.

Several studies have shown relationships between growth in early life and adult bone mass; in this article, we evaluate the relative contributions of pre- and postnatal factors to bone mass in the seventh decade. A total of 498 eight men and 468 women who were born in Hertfordshire during the period 1931-1939 and still living there were recruited. Detailed birth records were available. Participants attended a clinic where they completed a detailed health questionnaire, before performance of anthropometric measurements and bone densitometry of the proximal femur and lumbar spine (Hologic QDR 4500). Birth weight was associated with bone mineral content in both men (proximal femur: r=0.16, p=0.0003; lumbar spine: r=0.10, p=0.03) and women (proximal femur: r=0.16, p=0.0008; lumbar spine: r=0.11, p=0.03); relationships with bone mineral density were weaker and were significant at the proximal femur in men only (p=0.03). Relationships between weight at 1 y and bone mineral content were even stronger (proximal femur: men r=0.22, p<0.0001; women r=0.14, p=0.002). In men, 18% of the variance in proximal femoral bone area was explained by a model that included birth weight, weight at 1 y, and adult weight, with the relative contributions attributed to each being 2.8, 6.8, and 8.2%, respectively. In women, similar modeling produced figures of 6.7, 4.2, and 3.9% (overall variance of 15% in proximal femoral bone area). Hence, weight at each of these three points in the life course is important in the determination of adult bone mass, with greater contributions of earlier growth to bone size and mineral content than to bone mineral density.

Adult↗
PubMed2005

Static orthoses in the prevention of hand dysfunction in rheumatoid arthritis: a review of the literature.

Static orthoses are recommended for individuals who have early rheumatoid arthritis (Scottish Intercollegiate Guidelines Network, 2002; College of Occupational Therapists, 2003). These orthoses aim to rest and immobilize weakened joint structures and decrease local inflammation (Janssen et al., 1990; Nicholas et al., 1982); correctly position joints (Nordenskiöld, 1990; Ouellette, 1991); minimize joint contractures (McClure et al., 1994); increase joint stability (Kjeken et al., 1995); relieve pain (Feinberg, 1992; Callinan and Mathiowetz, 1996; Kjeken et al., 1995) and improve function (Janssen et al., 1990; Pagnotta et al., 1998; Nordenskiöld, 1990). Wrist and hand orthoses have been routinely prescribed for individuals with rheumatoid arthritis (RA) for the last 30 years with limited evidence that they are effective in achieving their purported aims. This article reviews the possible deterioration in hand structure that can occur in RA and discusses the theoretical basis for the application of static orthoses in RA. The evidence for the effectiveness of four commonly used static orthoses is then examined.

Journal Article↗
PubMed2005

Fetal programming of body composition and musculoskeletal development.

The prevalence of obesity, sarcopenia and osteoporosis is rising and there is increasing interest in determinants operating in early life. Fetal programming is the phenomenon whereby alterations in fetal growth and development in response to the prenatal environment have long term or permanent effects. Evidence for fetal programming of body composition and musculoskeletal development comes from epidemiological studies, investigation of the role of early undernutrition and preliminary findings on underlying mechanisms. Low birth weight and poor prenatal nutrition are associated with changes in adult body composition including altered fat distribution, reduced muscle mass and strength, and low bone mineral content. The mechanisms include a direct effect on cell number, altered stem cell function and resetting of regulatory hormonal axes. The next stage is translation of these findings into testable preventive strategies to maintain optimum body composition and minimize the risk of obesity, sarcopenia and osteoporosis in later life.

Body Composition↗
PubMed2005

Developmental origins of osteoporotic fracture: the role of maternal vitamin D insufficiency.

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most efforts in fracture prevention have been directed at retarding the rate of age-related bone loss and reducing the frequency and the 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 characterized 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 disassociation 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 (e.g., 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 endocrine systems such as the GH/IGF-1 and parathyroid hormone/vitamin D axes. Maternal vitamin D insufficiency is associated with reduced bone mineral acquisition during intrauterine and early postnatal life. Furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimization of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

Adult↗
PubMed2005

Diagnosis and epidemiology of osteoporosis.

PURPOSE OF REVIEW: Osteoporosis remains a major public health problem through its association with fragility fractures. Recent data suggest that the annual cost in Europe is 13 billion euros, mainly accounted for by hospitalisation after fracture. Understanding the epidemiology of osteoporosis is an essential step in developing strategies to reduce the burden of osteoporotic fracture in the population. RECENT FINDINGS: This article will review recent advances surrounding the epidemiology of osteoporosis, the burden of fracture in children and adults in this country and abroad, morbidity associated with such fractures, associations of disease and medication with fragility fracture, and advances in diagnostic techniques and identification of at-risk groups. SUMMARY: The papers studied highlight the wealth of high-quality research in this field, and they help in the visualisation of strategies to identify individuals at high risk of fragility fracture and to quantify fracture risk by measurement of bone density, bone quality, and risk factor algorithms.

Adolescent↗
PubMed2005

Mutation scanning by meltMADGE: validations using BRCA1 and LDLR, and demonstration of the potential to identify severe, moderate, silent, rare, and paucimorphic mutations in the general population.

We have developed a mutation-scanning approach suitable for whole population screening for unknown mutations. The method, meltMADGE, combines thermal ramp electrophoresis with MADGE to achieve suitable cost efficiency and throughput. The sensitivity was tested in blind trials using 54 amplicons representing the BRCA1 coding region and a panel of 94 unrelated family breast cancer risk consultands previously screened in a clinical diagnostic laboratory. All 10 common polymorphisms, 15/15 previously identified disease-causing mutations, and three previously untested single base changes were identified. Assays of LDLR exons 3 and 8 were validated in 460 familial hypercholesteremics and detected 8/9 known variants. We then applied the exon 3 assay in several DNA banks representing approximately 8000 subjects with known cholesterol values and applied both assays in one DNA bank (n = 3600). In exon 3 we identified one previously reported moderate mutation, P84S (n = 1), also associated with moderate hypercholesteremia in this subject; an unreported silent variant, N76N (n = 1); and known severe hypercholesteremia splice mutation 313+1G-->A (n = 2). Around exon 8 we identified a paucimorphism (n = 35) at the splice site 1061-8T-->C (known to be in complete linkage disequilibrium with T705I) and unreported sequence variants 1186+11G-->A (n = 1) and D335N G-->A (n = 1). The cholesterol value for D335N was on the 96.2 percentile and for T705I, 2/35 carriers were above the 99th percentile. Thus, variants with predicted severe, moderate, and no effect were identified at the population level. In contrast with case collections, CpG mutations predominated. MeltMADGE will enable definition of the full population spectrum of rare, paucimorphic, severe, moderate (forme fruste), and silent mutations and effects.

Breast Neoplasms↗