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Biomedical subjects

E Dennison

Publications and source records attributed to E Dennison.

At least 19 recordsLinked to original sources

Bone mineral status in immigrant Indo-Asian women.

BACKGROUND: Indo-Asian immigrants are known to be at high risk of metabolic bone disease, but the prevalence of osteoporosis in this population is unknown. AIM: To compare the bone mineral at the lumbar spine and femoral neck of Indo-Asian immigrant women with that of age-matched Caucasian women. DESIGN: Retrospective analysis. METHODS: Women of Indo-Asian origin referred for bone density scans in the last five years were identified. The skeletal status of each was compared with an age-matched Caucasian control for bone mineral content (BMC), bone mineral density (BMD) and bone mineral apparent density (BMAD) at the lumbar spine and femoral neck, and hip axis length was measured. RESULTS: At the lumbar spine, Indo-Asians had a significantly lower BMD than Caucasians (0.834 vs. 0.913, p = 0.008), but there was no significant difference when BMAD values were calculated (0.123 vs. 0.122). At the femoral neck, there was no difference in BMD (0.728 vs. 0.712, p = 0.5), and BMAD values were significantly higher among Indo-Asians than Caucasians (0.393 vs. 0.319, p = 0.022). Hip axis length was significantly shorter among Indo-Asian women (10.3 vs. 10.7, p = 0.009). DISCUSSION: Although Indo-Asian women appear to have lower spinal BMD than Caucasians, these differences disappear when BMAD values are calculated. While BMD is an areal density, not taking into account the 'depth' of the bone, BMAD is an estimation of volumetric density. Hence lower BMD values in Asians may be a size-related artefact. Longitudinal studies may be required to evaluate the use of BMD as a marker for fracture risk in this population.

Aged↗

Does birth weight predict adult serum cortisol concentrations? Twenty-four-hour profiles in the United kingdom 1920-1930 Hertfordshire Birth Cohort.

Low birth weight and weight in infancy are associated with adult insulin resistance and type 2 diabetes. A proposed mechanism is programming of the hypothalamic-pituitary-adrenal axis by intrauterine undernutrition, leading to persistently elevated cortisol concentrations. We examined 24-h serum cortisol profiles (samples every 20 min) in 83 healthy elderly men and women whose birth weight and infant weight were recorded. Variables derived from these profiles included trough, peak, and area under the curve concentrations; the time of onset, rate of rise, duration, and peak of the early morning cortisol rise; postprandial secretion; and regularity of secretion (approximate entropy). None of these parameters was related to birth weight, weight at 1 yr, or change in weight SD score between birth and 1 yr. Consistent with other studies, 0730-0900 h cortisol concentrations were higher in men and women of lower birth weight, although this was not statistically significant (P = 0.08). Our findings do not support the hypothesis that reduced intrauterine and infant growth are associated with continuously raised cortisol concentrations in old age. Programmed effects on the hypothalamic-pituitary-adrenal axis may influence reactivity rather than resting secretion.

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Epidemiology of osteoporosis.

This review has shown that osteoporosis is a major public health problem because of its association with fracture. It is now possible to predict future risk of fracture by measuring BMD with noninvasive techniques. The relation between BMD and fracture is comparable to that between blood pressure and stroke such that fracture risk can be assessed from a definition of osteoporosis using bone mass and past history of fracture. Because some of the risk factors for peak bone mass, involutional bone loss, and fracture are now characterized, coupled with innovative agents capable of retarding bone loss, it is becoming possible to generate preventive strategies, for the entire population as well as for those at highest risk.

Age Factors↗

Joint growth hormone and cortisol spontaneous secretion is more asynchronous in older females than in their male counterparts.

In humans, cortisol and GH are secreted in a pulsatile manner, and an interaction between GH and the hypothalamic-pituitary-adrenal axis has been established. In view of the sexually dimorphic pattern in GH secretion, we investigated the GH-cortisol bihormonal secretory dynamics in male and female healthy older individuals. We studied the GH and cortisol secretory patterns in 83 healthy subjects (45 men and 38 women; age range, 59.4-73.0 yr) by determining serum GH and cortisol concentrations at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol spontaneous secretion was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol patterns was computed at various time lags covering the 24-h period. Mean 24-h serum GH concentrations were significantly higher in females (mean, 1.31 mU/L; SD, 0.87) than in males (mean, 0.88 mU/L; SD, 0.42; P = 0.009), whereas mean 24-h serum total cortisol concentrations were higher in males (mean, 9.0 microg/dL; SD, 1.4) than in females (mean, 7.3 microg/dL; SD, 1.4; P = 0.0001). GH secretion was more irregular in females (mean ApEn, 0.81; SD, 0.23) than in males (mean ApEn, 0.60; SD, 0.20; P < 0.001). No significant difference in the regularity of cortisol secretion was noted between sexes. Cross-ApEn values of paired GH-cortisol were higher in females (mean, 1.15; SD, 0.18) than in males (mean, 1.01; SD, 0.16; P = 0.0003). Stepwise multiple linear regression analysis indicated that estradiol and insulin-like growth factor-binding protein-3 concentrations were independently related to GH ApEn values (r(2) = 0.14; P = 0.01), whereas cross-ApEn values of paired GH-cortisol were best predicted by FSH concentrations (r(2) = 0.37; P = 0.003). Cross-correlation analysis revealed a significant positive correlation between GH and cortisol, peaking at lag time of 4.7 h in males (r = 0.30; P < 0.0001) and 4.3 h in females (r = 0.14; P < 0.0001), with GH leading cortisol by these time intervals. In addition, a significant negative correlation between the two hormones was noted over time, peaking at 4.7 h in males (r = -0.21; P < 0.0001) and 6.3 h in females (r = -0.25; P < 0.0001), with cortisol leading GH by these time intervals. The above results indicate that in the elderly, females have a more disordered GH secretory pattern and a more asynchronous joint GH-cortisol secretion than their male counterparts. These observations most likely reflect bidirectional interactions between the GH and hypothalamic-pituitary-adrenal axis in humans as well as diminution of subsystem integrity and synchronous control of interconnected hormonal systems with advancing age.

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An investigation of the diagnostic value of bilateral femoral neck bone mineral density measurements.

This paper describes a study to assess the clinical value of bilateral femoral neck bone mineral density (BMD) measurements. Although a range of factors will determine clinical decisions, the classification of the site with the lowest T-score is likely to have significant bearing on the management of a patient. While it is common practice to measure BMD at the lumbar spine and a single neck of femur, knowledge of the BMD of the second femur may also be of diagnostic value. Using dual-energy X-ray absorptiometry, BMD of the lumbar spine and right and left femoral neck was measured in a group of 2372 white, Caucasian women (mean age +/- SD, 56.6 +/- 13.9 years) routinely referred for bone densitometry. Analysis of the measurements showed a significant (p = 0.02) but small difference between the mean BMD of the right (0.840 +/- 0.152 g/cm2) and left (0.837 +/- 0.150 g/cm2) femoral neck. Further investigation of femur scans revealed 79 (3.3%) patients in whom one side was osteoporotic while the other side and spine were normal or osteopenic using the World Health Organization diagnostic criteria in combination with manufacturer's reference data. Patients in whom the femoral neck BMD measurements differed by less than the precision error of the system were then excluded. This left only 51 (2.2%) patients, that is 29 (1.2%) for right femur and spine scan and 22 (0.9%) for left femur and spine scan, in whom knowledge of both femoral neck BMD measurements could have altered the classification of the lowest site assessed to osteoporotic. These data suggest that there is only a small benefit from performing bilateral femoral neck BMD measurements. Since BMD measurements are only one of a range of factors considered as part of a patient's management, it is suggested that the extra time, cost and radiation dose associated with measurement of the second femur may not be justified.

Absorptiometry, Photon↗

Epidemiology of osteoporotic fractures.

Osteoporosis constitutes a major public health problem through its association with age-related fractures. These fractures typically occur at the hip, spine and distal forearm. It has been estimated that the lifetime risk of a hip fracture in white women is 17.5%, with a comparable risk in men of 6%. Hip fractures lead to an overall reduction in survival of about 15% (relative or observed/expected survival at 5 years of 0.83), and the majority of excess deaths occur within the first 6 months following the fracture. Such fractures are also associated with considerable morbidity. Although all vertebral deformities do not come to clinical attention, the lifetime risk of clinically diagnosed vertebral fractures is about 15% in white women. Vertebral fractures tend to be associated with back pain and kyphosis, and also with an impairment of survival, though this is likely to be due to clustering of comorbidity. About one-quarter of clinically diagnosed vertebral deformities result in hospitalization.

Adult↗

Epidemiology of chronic disc degeneration and osteoarthritis of the lumbar spine in Britain and Japan: a comparative study.

OBJECTIVE: To compare the prevalence of spinal osteoarthritis (OA) in Britain and Japan. METHODS: A total of 206 men and 188 women living in Hertfordshire, UK, and a total of 100 men and 100 women living in Miyama, Japan, aged 60-79 years were studied. Participants completed a lifestyle questionnaire, and anteroposterior and lateral radiographs of the thoracic and lumbar spine were obtained under standardized conditions. Each lumbar radiograph was graded for osteoarthritic changes according to the overall Kellgren-Lawrence (K-L) score. Gradings were also recorded separately for disc narrowing and osteophyte formation. RESULTS: British subjects were much more likely to have lumbar spine radiographs graded as K-L grade 4 severity (p = 0.05 in men, p < 0.001 in women). British men displayed a greater prevalence of disc narrowing (p = 0.08), but less severe osteophytosis (p = 0.06) than their Japanese counterparts. British women displayed more severe disc narrowing (p < 0.001) and osteophyte formation (p < 0.001). On multiple regression analysis, a higher body mass index (BMI) was associated with excess risk in the British population (OR 1.84, 95% CI 1.12-3.02), but not in the Japanese population. Differences between countries in K-L severity persisted after allowing for age and BMI, suggesting that differences in body build could not fully explain differences in lumbar spine OA in the 2 countries. CONCLUSION: We found that severe lumbar degenerative disease is more common in the UK than in a mountain village in Japan, and that differences exist in the prevalence of both osteophytosis and disc degeneration between the 2 countries.

Aged↗

Determinants of bone loss in elderly men and women: a prospective population-based study.

While several studies have described the rate and pattern of involutional bone loss in women, far less information is available for men. Furthermore, the roles of lifestyle and body build in determining bone loss rate in both sexes have been largely extrapolated from cross-sectional studies. We addressed this issue in a population-based longitudinal study which sought to ascertain rates of bone loss at the femoral neck and lumbar spine in a cohort of men and women aged 60-75 years at baseline, and to relate this loss to anthropometric and lifestyle variables. We additionally investigated the capacity of biochemical markers of bone turnover to predict bone loss rates in these subjects. Women lost bone at all sites; this ranged from 0.20%/year at the lumbar spine to 1.43%/year at the femoral trochanteric region. By contrast, men lost only 0. 20%/year at the trochanteric region, and gained at the lumbar spine (0.33%/year) and at Ward's triangle (0.27%/year) over the 4-year period. Anthropometric measurements were associated with bone loss in both sexes; lower baseline body mass index (BMI) and a greater rate of loss of adiposity over the follow-up period were both associated with greater bone loss at all proximal femoral sites. These attained statistical significance after Bonferroni correction at the total proximal femur among both men (r = 0.29), p<0.01) and women (r = 0.31, p<0.05). Lifestyle factors associated with lower rates of bone loss (after adjustment for BMI) included alcohol consumption at the femoral neck among women (p = 0.007) and physical activity at the lumbar spine among men (p = 0.05). Serum parathyroid hormone, 25-hydroxyvitamin D and biochemical markers of bone turnover did not predict bone loss after adjustment for adiposity.

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A sexually dimorphic pattern of growth hormone secretion in the elderly.

In rodents, the sexually dimorphic pattern of pulsatile GH secretion is an important determinant of growth, liver enzyme function and insulin-like growth factor I (IGF-I) expression. Whether this difference is present in humans at different ages is unclear. We studied GH secretory patterns in the elderly by constructing 24-h serum GH profiles in 45 male and 38 female (age, 59.4-73.0 yr) volunteers and related patterns to IGF-I, IGF-binding protein-3 (IGFBP-3), and GH-binding protein levels; body mass index; and waist/hip ratio. Serum GH concentrations were measured in samples drawn at 20-min intervals and analyzed using a sensitive chemiluminescent assay (Nichols Institute Diagnostics: sensitivity, 0.036 mU/L). The 24-h serum GH profiles were analyzed using a concentration distribution method to determine GH peak and trough levels, spectral analysis, and assessment of serial irregularity by approximate entropy (ApEn). There was a highly significant difference in mean 24-h serum GH concentrations in females compared to males (males, 0.88 mU/L; females, 1.31 mU/L; P = 0.009) as a result of significantly higher trough GH levels (males, 0.04 mU/L; females, 0.16 mU/L; P < 0.001). Peak values were not significantly different. Serum IGF-I levels were significantly higher in males (males, 162.4 ng/mL; females, 87.8 ng/ mL; P < 0.001). Peak GH values were related to serum IGF-I levels (males: r = 0.39; P = 0.009; females: r = 0.5; P = 0.002), whereas trough GH levels were not. IGFBP-3 levels were similar and related to GH peaks only in males (r = 0.32; P = 0.03). GH was secreted with a dominant periodicity of 200 min in males and 280 min in females (P < 0.025). The proportion of time taken up by regular oscillatory activity was less in females (females, 11.1%; males, 14.7%; P = 0.01). GH secretion assessed by ApEn was more disordered in females (males, 0.60; females, 0.81; P < 0.001), and increasing disorder was associated with lower IGF-I levels. Body mass index was negatively related to GH in both sexes. In males, trough values were the major determinant (r = -0.31; P = 0.04), whereas in females, the peak value was the major determinant (r = 0.35; P = 0.04). Trough GH levels were inversely related in both sexes to waist/hip ratio (males: r = -0.40; P = 0.006; females: r = -0.44; P = 0.006) and to increasing secretory disorder (ApEn; r = -0.46; P < 0.001). These data demonstrate a sexually dimorphic pattern of GH secretion in the elderly.

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Profiles of endogenous circulating cortisol and bone mineral density in healthy elderly men.

Exogenous glucocorticoids are known to increase the risk of osteoporosis. However, the contribution made by endogenous circulating cortisol concentrations to adult skeletal status remains unknown. We examined this issue in a sample of 34 healthy men, aged 61-72 yr. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of serum cortisol and cortisol-binding globulin. Bone mineral density was measured at the lumbar spine and proximal femur using dual energy x-ray absorptiometry. Measurements were made at baseline and 4 yr later. There was a weak negative association between integrated cortisol concentration and lumbar spine bone density (r = -0.37; P < 0.05); similar relationships (P < 0.05) existed at three of five proximal femoral sites. There were also statistically significant positive associations between the trough cortisol concentration and bone loss rate at the lumbar spine (r = 0.38; P < 0.05), femoral neck (r = 0.47; P < 0.001), and the trochanteric region (r = 0.41; P = 0.02) over the 4-yr follow-up period. The cross-sectional relationships between cortisol concentration and bone density were removed by adjustment for body mass index, but the influence on bone loss rate remained significant after adjusting for adiposity, cigarette smoking, alcohol consumption, dietary calcium intake, physical activity, and serum testosterone and estradiol levels. These observations suggest that the endogenous cortisol profile of healthy elderly men is a determinant of their bone mineral density and their rate of involutional bone loss.

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The epidemiology of Paget's disease in Britain: is the prevalence decreasing?

To estimate changes in the age- and gender-specific prevalence of Paget's disease in Britain, we performed a radiographic survey of the disorder in 10 British centers, using sampling and radiographic methods identical to a study performed in 1974. In each center, a sample of abdominal radiographs of people aged 55 years and over was taken from stored films within the radiology department of the principal general hospital. The radiographs were identified by screening radiographic records over the period 1993-1995. Any abdominal radiograph in a subject aged 55 years and over which included the entire pelvis, sacrum, femoral heads, and all lumbar vertebrae was studied. The radiographs were evaluated by a trained observer and the consultant radiologist who participated in the original 1974 survey. Nine thousand eight hundred and twenty-eight radiographs (4625 men, 5203 women) were assessed in the 10 towns. The overall age/gender standardized prevalence rate was 2%, with a male/female ratio of 1.6. Prevalence increased steeply with age among men and women, rising to 6.9% of men and 5.8% of women aged 85 years and over. The prevalence of Paget's disease in the 10 towns in 1994 was only 40% of that observed during the 1974 study. The decline in prevalence was apparent in all 10 centers, but was most marked in those with high rates in the original study. This survey of Paget's disease in 10 British towns suggests a prevalence of 2.5% among men and 1.6% among women aged 55 years and over. Age-adjusted prevalence rates declined steeply between 1974 and 1994. These declines suggest an environmental contribution to the etiology of this disorder that requires further investigation.

Age Factors↗

Bone loss in Great Britain and Japan: a comparative longitudinal study.

Hip fracture incidence is lower in Japan than in the West. Although differences have been found in peak bone mass and hip geometry between white and Japanese populations, these do not fully explain the difference in hip fracture rates. Variation in the rates of involutional bone loss may be an additional contributing factor. We address this issue in a prospective epidemiological study comparing bone loss rate among elderly people in Britain and Japan. Two population-based studies of bone loss rate in a British and a Japanese cohort were performed. Annual bone loss rates were obtained for 172 Hertfordshire men and 143 Hertfordshire women of mean age 66 years, and a questionnaire administered to obtain information on known confounding lifestyle factors. Eighty-six Japanese men and 90 Japanese women of mean age 69 years completed a similar study in Taiji, Japan. British men and women were heavier than Japanese men and women. Differences in lifestyle were also evident; the British men were less likely to smoke and the women more likely to consume alcohol than their Japanese counterparts. The British population also spent more time walking outdoors. Statistically significant differences between the two populations were apparent in baseline bone mineral density at lumbar spine (p < 0.05) and trochanter (p < 0.001) in men and women with Japanese subjects having lower values. There were also significant differences in bone density at the femoral neck (p < 0.001) between British and Japanese males. Men gained bone at the lumbar spine over the follow-up period in both populations. Bone loss rates were generally greater in the British female population than in Japanese women: the difference was statistically significant at the femoral neck (p < 0.05) and femoral trochanter (p < 0.001). These differences all remained significant after adjustment for differences in age between the two populations. Japanese subjects appear to have lower peak bone mass, but slower bone loss rates in later life than their European counterparts. These differences in bone loss rate help to explain the relatively low hip fracture rates found in Japan.

Absorptiometry, Photon↗