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Biomedical subjects

Cyrus Cooper

Publications and source records attributed to Cyrus Cooper.

At least 73 records · Page 4Linked to original sources
PubMed2004

Birth weight, weight at 1 y of age, and body composition in older men: findings from the Hertfordshire Cohort Study.

BACKGROUND: Size in early life is related to adult body mass index, and early environmental influences have been proposed to have lifelong consequences for obesity. However, body mass index also reflects fat-free mass, and few studies have examined the relation between size in early life and direct measures of body composition in older people. OBJECTIVE: We investigated the associations of birth weight and weight at 1 y of age with body composition in older men. DESIGN: We carried out a retrospective cohort study in Hertfordshire, United Kingdom. Men who were born between 1931 and 1939 and for whom there were records of birth weight and weight at 1 y of age (n = 737) participated in the study. The main outcome measures were adult body mass index, fat-free mass, and fat mass. RESULTS: Birth weight was significantly and consistently positively associated with adult body mass index and fat-free mass but not with measures of adult fat mass. In contrast, weight at 1 y of age was associated with adult body mass index, fat-free mass, and fat mass. CONCLUSIONS: The consistently reported positive relation between birth weight and adult body mass index may reflect prenatal and maternal influences on fat-free mass rather than on fat mass in older people. The postnatal environment may be more influential than prenatal factors in the development of obesity in later life.

Adipose Tissue↗
PubMed2004

Does sarcopenia originate in early life? Findings from the Hertfordshire cohort study.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging. Recent epidemiological studies have shown that men and women who grew less well in early life have lower muscle strength. Our objective was to investigate the relationship between birth weight, infant growth, and the development of sarcopenia. METHODS: We studied 730 men and 673 women, of known birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between 1931 and 1939. Participants completed a health questionnaire, and we measured their height, weight, and grip strength. Standard deviation scores for birth weight, and for infant growth conditional on birth weight, were analyzed in relation to grip strength before and after adjustment for adult size. RESULTS: Grip strength was most strongly associated with birth weight in men (r = 0.19, p < .001) and women (r = 0.16, p < .001). These relationships remained significant after adjustment for adult height and weight. In contrast, the associations with infant growth were weakened after allowing for adult size. Adjustment for age, current social class, physical activity, smoking, and alcohol did not affect these results. CONCLUSIONS: Birth weight is associated with sarcopenia in men and women, independently of adult height and weight. The influence of infant growth on long-term muscle strength appears to be mediated through adult size. Sarcopenia may have its origins in early life, and identifying influences operating across the whole life course may yield considerable advances in developing effective interventions.

Adult↗
PubMed2004

Growth hormone replacement in adults and bone mineral density: a systematic review and meta-analysis.

BACKGROUND: The effect of GH replacement on bone mineral density (BMD) in adults with GH deficiency (GHD) is uncertain. We carried out a systematic review of randomized trials that compared GH to no active treatment, with BMD as an outcome. METHODS: We searched electronic databases to identify articles, abstracts and conference proceedings to March 2002. We also checked reference lists in included studies and expert reviews. Two reviewers independently extracted the data on study design and change in BMD. The results of individual trials were combined by fixed effects model meta-analysis using weighted mean difference (WMD) of change in BMD at the lumbar spine (our primary outcome) and other sites. FINDINGS: Eighteen trials that included 700 patients met the inclusion criteria. Maximum follow-up was for 12 weeks (1 trial), 6 months (14 trials), 12 months (1 trial), 18 months (1 trial) and 24 months (1 trial). Reporting quality of both study design and results was poor. Ten trials (458 subjects) were included in the meta-analysis. We excluded those eight trials from which sufficient data could not be extracted. We found a mean change in BMD, at the lumbar spine with GH treatment, of 0.01 g/cm2 after 6 and 12 months, 0.02 g/cm2 after 18 months and 0.03 g/cm2 after 24 months. Statistical significance at the 0.05 level was just achieved at 6 and 12 months but was significant at 18 and 24 months. These changes are small and may be influenced by bias. CONCLUSION: There is evidence of a small effect of GH replacement on bone mineral density in adults with GH deficiency. The clinical importance of this is uncertain.

Adult↗
PubMed2004

Late life metabolic syndrome, early growth, and common polymorphism in the growth hormone and placental lactogen gene cluster.

Low rates of fetal and infant growth are associated with the metabolic syndrome and cardiovascular disease in later life. We investigated common genetic variation in the GH-CSH gene cluster on chromosome 17q23 encoding GH, placental lactogens [chorionic somatomammotropins (CSH)], and placental GH variant in relation to fetal and infant growth and phenotypic features of the metabolic syndrome in subjects aged 59-72 yr from Hertfordshire, UK. Allele groups T, D1, and D2 of a locus herein designated CSH1.01 were examined in relation to GH-CSH single nucleotide polymorphisms and to specific phenotypes. Average birth weights were similar for all genotype groups. Men with T alleles were significantly lighter at 1 yr of age, shorter as adults, and had higher blood pressures, fasting insulin (T/T 66% higher than D2/D2) and triglyceride concentrations, and insulin and glucose concentrations during a glucose tolerance test. Birth weight and 1-yr weight associations with metabolic syndrome traits were independent of the CSH1.01 effects. Common diversity in GH-CSH correlates with low 1-yr weight and with features of the metabolic syndrome in later life. GH-CSH genotype adds substantially to, but does not account for, the associations between low body weight, at birth and in infancy, and the metabolic syndrome.

Aged↗
PubMed2004

The developmental origins of osteoporotic fracture.

Undernutrition and other adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology and metabolism. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the GH/IGF-1 and HPA axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have suggested that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Finally, childhood growth rates have been directly linked to the risk of hip fracture many decades later. Further work is needed to use this approach to develop novel therapeutic and preventative strategies to reduce the burden of osteoporotic fractures in the population.

Female↗
PubMed2004

Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk.

Low bone mineral density (BMD) is correlated with increased fracture risk. Whether greater BMD increases induced by osteoporosis drugs are related to greater decreases in fracture risk is controversial. We analyzed the relationship between BMD change and fracture risk in postmenopausal osteoporotic women receiving antiresorptive treatment. The analysis combined data from three pivotal risedronate fracture end-point trials. Women received risedronate (n = 2047) or placebo (n = 1177) daily for up to 3 yr. The BMD and vertebral radiographs were assessed periodically during 3 yr. The estimated risk of new vertebral fracture was compared between patients whose BMD increased and those whose BMD decreased. Risedronate-treated patients whose BMD decreased were at a significantly greater risk (p = 0.003) of sustaining a vertebral fracture than patients whose BMD increased. The fracture risk was similar (about 10%) in risedronate-treated patients whose increases in BMD were < 5% (the median change from baseline) and in those whose increases were >/= 5% (p = 0.453). The changes in lumbar spine BMD explained only 18% (95% confidence interval [CI], 10%, 26%; p < 0.001) of risedronate's vertebral fracture efficacy. Although patients showing an increase in BMD had a lower fracture risk than patients showing a decrease in BMD, greater increases in BMD did not necessarily predict greater decreases in fracture risk.

Absorptiometry, Photon↗
PubMed2004

Risk factors for knee osteoarthritis in Japanese women: heavy weight, previous joint injuries, and occupational activities.

OBJECTIVE: Risk of knee osteoarthritis (OA) associated with constitutional factors, history of joint injuries, and occupational factors was assessed in a case-control study among women in Japan. Results were contrasted with a comparable study in Britain. METHODS: The study covered 3 health districts in Japan. Cases were women aged >/= 45 years old, diagnosed with knee OA by orthopedic physicians utilizing radiography. No cases displayed established causes of secondary OA. Controls selected randomly from the general population were individually matched to each case for age, sex, and residential district. Subjects were interviewed using structured questionnaires to determine medical history, including history of joint injury, physical activity, socioeconomic factors, and occupation. Height and weight were measured. RESULTS: Interviews were obtained from 101 female cases and controls. The highest third of heaviest body weight in the past [high (> 62.0 kg) vs low (< 55 kg) odds ratio = 4.42, 95% confidence interval 1.17-16.64], previous injury to the knee (OR 7.11, 95% CI 2.40-21.09), sedentary work during initial employment (OR 0.35, 95% CI 0.15-0.84), and total working years (OR 1.05, 95% CI 1.01-1.08) represented independent factors associated with knee OA, after controlling for other potential risk factors. CONCLUSION: Heavy weight in the past appears to represent a risk factor for knee OA among women in Japan, as reported in Britain. Constitutional factors may represent important determinants for knee OA, regardless of race. Previous injury to the knee and occupational factors are also associated with knee OA in both Britain and Japan, although characteristic activities for work vary.

Aged↗
PubMed2003

Evidence of sustained skeletal benefits from impact-loading exercise in young females: a 3-year longitudinal study.

UNLABELLED: The skeletal effects from intensive exercise throughout puberty are undefined. Forty-five female gymnasts and 52 controls were studied over 3 years, including a heredity aspect. The effects of size, maturity, exercise, and diet were identified using a multilevel regression model. Results demonstrated sustained skeletal benefits resulting from exercise throughout all stages of pubertal development. INTRODUCTION: Weight-bearing exercise is beneficial for peak bone mass development. However, whether skeletal benefits achieved with exercise are maintained if training remains intensive throughout the pubertal years is not entirely clear. The influence of familial resemblance for bone mass remains undefined in physically active versus inactive children. The aim of this study was to investigate the long-term influences of impact-loading exercise on bone quantity and quality in young females after controlling for growth, maturation, and hereditary factors. MATERIALS AND METHODS: At baseline, 45 gymnasts (G) and 52 normally active controls (C) 8-17 years of age were recruited. Anthropometry, diet, physical activity, and quantitative ultrasound (QUS) were measured annually for 3 consecutive years. DXA scans of total body (TB) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) were taken three times at 1-year intervals. A multilevel regression model was fitted, and the independent effects of body size, maturity, physical activity, and diet were identified over time. To assess heredity influences, 27 G mothers and 26 C mothers volunteered for cross-sectional measurements of anthropometry, QUS, and BMC/BMD. RESULTS AND CONCLUSIONS: Gymnasts were smaller and lighter (as were their mothers) than controls, but they had significantly higher QUS and axial and appendicular BMC and BMD, with > 170 g more bone mineral in TB across puberty (after adjustment for maturity [years from peak height velocity], height, weight, energy, and protein intake). Gymnasts had up to 24-51% higher BMC and 13-28% higher BMD, depending on skeletal site. These results provide evidence of sustained skeletal benefits from impact-loading exercise, which are unlikely to result entirely from heredity, throughout pubertal years.

Absorptiometry, Photon↗
PubMed2003

Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses.

UNLABELLED: Published meta-analyses have investigated the relationship between changes in BMD and fracture risk reduction observed with antiresorptive agents, with inconsistent results. Many factors may affect the outcome of such analyses. Our work explores some of these factors and illustrates the need for caution in interpreting the results of meta-analyses. INTRODUCTION: The role of the increase in bone mineral density (BMD) in fracture risk reduction observed in osteoporotic patients treated with antiresorptive drugs is unclear. We examined the effects of study selection, the use of summary statistics or individual patient data (IPD) as the basis for the analyses, and the choice of BMD values used on the outcome of meta-analyses. MATERIALS AND METHODS: To evaluate the effects of study selection, we performed Poisson regression analyses using the results from a number of published studies. To evaluate the effects of using individual patient data instead of summary statistics, we simulated the IPD for vertebral fracture to match the summary statistics for published trials and compared these results with those based on meta-regression using summary statistics. We also evaluated the effect of varying the BMD increase with treatment (3-8%) used in predicting the fracture risk reductions in these simulations. RESULTS: The Poisson regression, which found a statistically significant relationship between nonvertebral fracture risk and spinal BMD when 18 trials of varying designs, duration, and sample size were included in the analysis (p = 0.02), was no longer significant when the analysis was based on the 7 large studies that were placebo-controlled, at least 3 years in duration (at least 1000 patient-years). Meta-analyses of simulated IPD from 12 trials of six antiresorptive agents gave accurate results regardless of the proportion of vertebral risk reduction assumed to be related to BMD change, whereas meta-regression based on summary statistics always produced an estimate around 50%. When the actual data from two risedronate studies were analyzed, the meta-regression based on summary statistics demonstrated a stronger correlation between BMD change and fracture risk reduction than the results based on the IPD analysis. In predicting the fracture risk reduction, the use of the average BMD gain (3%) observed in all studies in the calculations produced an overall fracture risk reduction very similar to the one observed clinically. In contrast, the use of a large BMD gain (8%) produced a substantially higher estimated fracture risk reduction and resulted in a high proportion of fracture risk reduction being attributed to BMD change. CONCLUSIONS: Many factors may influence the outcome of meta-analyses, and caution should be used in interpreting the results of such analyses when exploring the relationship between BMD changes and fracture risk reduction with antiresorptive therapy of osteoporosis.

Bone Density↗
PubMed2003

PTH/PTHrP activity and the programming of skeletal development in utero.

There is increasing evidence that nutritional deficiency in utero adversely affects bone development and the risk of developing osteoporosis in later life. Although the mechanisms involved are unknown, circumstantial evidence points to an important role of PTH/PTHrP activity. It is recognized that PTH and PTHrP are critically involved in regulating fetal calcium homeostasis, actions that are mediated at least in part by PPR. As well as playing a central role in the maintenance of calcium homeostasis in the fetus, studies in transgenic mice show that PTH, PTHrP, and PPR exert similar effects on skeletal development in utero, acting to increase the size of the trabecular envelope and decrease that of the cortical envelopes. Taken together, these observations raise the possibility that stimulation of PTH/PTHrP activity in the fetus in response to calcium deficiency acts to increase the size of the trabecular envelope but to reduce that of the cortical envelope. Although any increase in trabecular bone at birth is likely to be relatively transient, a decrease in size of the cortical envelope may have a persistent effect on the trajectory of bone growth in subsequent childhood. Consistent with this proposal, preliminary findings from birth cohort studies suggest that maternal calcium intake and cord blood calcium levels are positively related to bone mass of the offspring as assessed later in childhood. Further studies are justified to determine whether alterations in fetal PTH/ PTHrP activity caused by calcium stress lead to a reduction in size of the cortical envelope at birth that persists into childhood and later adult life and to identify modifiable maternal factors that are responsible for these changes.

Bone Development↗
PubMed2003

Anatomic distribution of sensory symptoms in the hand and their relation to neck pain, psychosocial variables, and occupational activities.

To explore whether different distributions of numbness and tingling in the hand can be usefully distinguished in epidemiologic studies of disorders such as carpal tunnel syndrome, the authors used a postal questionnaire, an interview, and a physical examination to collect information about risk factors, symptoms, and signs from a general population sample of 2,142 adults in Southampton, England, during 1998-2000. The authors distinguished six distributions of numbness and tingling and compared their associations with other clinical findings and with known risk factors for upper limb disorders. Distinctive relations were found for symptoms that involved most of the palmar surface of the first three digits but not the dorsum of the hand or the little finger. Such symptoms were more often associated with positive Phalen's and Tinel's tests and, unlike other categories of sensory disturbance, were not related to neck pain or restriction of neck movement. They also differed in showing no association with lower vitality or poorer mental health but an association with repeated wrist and finger movements at work. These findings suggest that, in the classification of numbness and tingling of the hand, it may be useful to distinguish symptoms that involve most of the sensory distribution of the median nerve but not other parts of the hand.

Adult↗
PubMed2003

Patterns of interphalangeal hand joint involvement of osteoarthritis among men and women: a British cohort study.

OBJECTIVE: To characterize the pattern of involvement of osteoarthritis (OA) of the hand among men and women of the same age. METHODS: Structured hand examinations were performed on 1,467 men and 1,519 women who were age 53 years and born in England, Scotland, or Wales during the first week of March 1946 (identified through the United Kingdom National Survey of Health and Development). OA at each joint site was characterized using a previously validated examination schedule. The interrelationship of involvement of different hand joints was analyzed by logistic regression and cluster analyses. RESULTS: There was clear evidence of polyarticular involvement in the hand joints of both the men and the women. Among the women, 161 subjects had >/=4 joints involved, compared with only 41 subjects expected in this category (P < 0.001). Among the men, 87 subjects were observed to have >/=4 joints involved, in contrast with only 7 subjects expected (P < 0.001). The pattern of hand joint involvement (characterized by clustering primarily by row and symmetric joint involvement, rather than clustering by ray) was found to be almost identical between the men and the women. CONCLUSION: This study confirms the existence of a polyarticular subset of OA among men that has characteristics similar to those of the variant observed among women. The data suggest that the genetic or metabolic influences underlying this particular variant of OA acts similarly in both sexes.

Cluster Analysis↗
PubMed2003

PASSCLAIM - Bone health and osteoporosis.

BACKGROUND: The EC Concerted Action PASSCLAIM aims to produce a generic tool for assessing the scientific support for health-related claims for foods and food components. AIM: The task of the ITGB Working Group was to critically evaluate the categories of scientific evidence needed to support claims in relation to bone health and osteoporosis. METHODS: A framework was developed to describe the chain of evidence that is required to link the consumption of a food or food component to bone health outcomes. Techniques available for interrogating each link in the chain were identified and their strengths and weaknesses considered. This framework was used to determine intermediate markers of health outcome with respect to osteoporosis and to debate the level of evidence that would be required to substantiate claims of enhanced function or reduced disease risk. RESULTS: Use of this framework with osteoporotic fracture as the health endpoint resulted in the following judgements based on current knowledge: 1) bone mineral density (BMD) is an intermediate marker of bone health which, for people of any age and sex, can provide evidence of enhanced function; 2) for people over 50 years living in populations with a high incidence of fracture, BMD is an intermediate marker of osteoporotic fracture risk which can provide evidence of an increased probability of reduced disease risk; 3) because osteoporosis is defined as a state of increased fracture risk due to low bone mass and deterioration in bone microarchitecture, a claim of a definite reduction in osteoporosis or fracture risk requires similar substantiation to claims that fractures are prevented or treated, including clinical trials and animal studies; 4) data from lower in the chain of evidence, such as bone turnover and calcium bioavailability, are not, by themselves, sufficiently strongly related to bone health endpoints to provide evidence of enhanced function or reduced disease risk but can provide supporting information. CONCLUSIONS: In the light of existing scientific knowledge, a framework has been developed as a tool for considering the scientific support for claims relating to bone health and osteoporosis. To provide a working example, the framework has been used to assess the current position with osteoporotic fracture as the health endpoint. This experience will contribute to the formulation under PASSCLAIM of a generic tool for assessing the scientific support of health claims on foods.

Animals↗
PubMed2003

Catabolic and anabolic phases of osteodystrophy in aged rats.

The aims of this study were to investigate the incidence and characteristics of osteodystrophy that occurred in rats which were maintained until death without experimental intervention. We defined and characterized catabolic and anabolic phases of osteodystrophy, based on the morphology of the cortical bone. During the catabolic phase, large resorption cavities appeared within the cortical bone. During the anabolic phase, progressively increased amounts of new bone was formed, which partially or completely filled previous resorption cavities and also extended into the medullary space. Contrary to previous experimental studies of renal failure in rats, which documented suppression of bone formation, the present studies found that the majority of rats displayed evidence of an anabolic phase with extensive new bone formation. The new bone originated within and around fibers that had formed adjacent to bone trabeculae or within resorption cavities. Hence, osteitis fibrosa was a preliminary stage to de novo bone formation. There was an association between the incidence of osteodystrophy and kidney failure as the cause of death, and it is proposed that the observed osteodystrophy had been a consequence of secondary hyperparathyroidism due to renal failure.

Aging↗
PubMed2003

Determinants of fracture risk in osteoporosis.

Osteoporosis is a major public health issue, with fragility fractures of the hip, vertebrae, and distal radius considered the most important consequences. These lead to increased morbidity, mortality, hospital care, and dependency. The risk factors for the development of fragility fractures are numerous and involve genetic and environmental influences, as well as an interaction between the two. In this review, the recent literature examining genetic factors, possible candidate genes, the evolving area of intrauterine fetal programming, and anthropometric and environmental factors will be reviewed.

Adrenal Cortex Hormones↗
PubMed2003

Soft-tissue rheumatic disorders of the neck and upper limb: prevalence and risk factors.

OBJECTIVES: To review the epidemiologic literature concerning the occurrence of and the risk factors for pain and specific soft-tissue rheumatic conditions that affect the neck and upper limbs. METHODS: An extensive search of the literature, including a search of Medline and EMBASE, authoritative recent reviews, and relevant textbooks, was performed. Studies that furnished data about the occurrence of or risk factors for regional pain or specific soft-tissue entities were extracted. RESULTS: Numerous epidemiologic studies among different populations suggest a high prevalence of pain in the neck (10% to 19%), shoulder (18% to 26%), elbow (8% to 12%), and wrist/hand (9% to 17%) at any point in time. Less clear is the proportion of pain caused by specific upper-limb disorders as compared with nonspecific pain; however, as many as 6% of adults may have carpal tunnel syndrome. Significant risk factors for these disorders include age, female gender, obesity, and association with mechanical exposures (eg, posture, force, repetition, vibration) in the workplace. Also implicated are psychologic well-being and psychosocial workplace factors such as high levels of demand, poor control, and poor support. CONCLUSION: Pain and soft-tissue rheumatic disorders of the neck and upper limb are common. It appears that individual, mechanical, and psychosocial factors all contribute to upper-limb disorders, suggesting that future strategies for prevention will need to address each of these factors if they are to be successful.

Humans↗
PubMed2003

Criteria for assessing pain and nonarticular soft-tissue rheumatic disorders of the neck and upper limb.

OBJECTIVE: To critically review the criteria used to diagnose nonarticular soft-tissue rheumatic disorders of the neck and upper limb. METHODS: An extensive search of the literature, including a search of Medline and EMBASE, authoritative recent reviews, and relevant textbooks, was completed. The diagnostic criteria used in epidemiologic studies were compared and the reliability and validity of these criteria were assessed. RESULTS: Altogether, the search identified 117 relevant research articles, among which 69 included a physical examination component, but few specified diagnostic criteria. Evidence supported respectable levels of between-observer repeatability regarding: symptom questionnaires (kappa, 0.52 to 0.79); measurement of shoulder range of motion with a goniometer (intraclass coefficients > 0.70); tests for carpal tunnel syndrome (Tinel's and Phalen's kappa, 0.53 to 0.80); and demonstration of neck tenderness (kappa = 0.43). The Katz hand diagram, and combinations of physical signs of carpal tunnel syndrome, show reasonable sensitivity and specificity for that diagnosis but only among patients referred to specialists with that putative diagnosis; no such validity has been shown among the general population. Only 1 diagnostic examination schedule has published data on both the reliability and the validity of its criteria and diagnoses. For the remaining soft-tissue upper-limb disorders, diagnostic criteria rely apparently on face and content validity and reliability data have not been published. CONCLUSION: Classification of specific disorders of the neck and upper limb requires a back to basics approach. At present, the diagnosis of most of these conditions relies heavily on the clinical opinions of investigators and there are insufficient data to indicate that these criteria are repeatable, sensitive, or specific. Recent European initiatives offer scope to follow a more disciplined approach, but more work is urgently required.

Humans↗