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Biomedical subjects

N A Pocock

Publications and source records attributed to N A Pocock.

At least 37 records · Page 2Linked to original sources

Genetic factors in bone turnover.

Genetic factors are major determinants of adult bone density, however, it is unknown how these effects may be mediated. Since bone mineral density is the net result of bone formation and bone resorption we studied biochemical indices of bone formation (serum osteocalcin) and resorption [fasting urinary calcium:creatinine (Ca/Crt) and hydroxyproline:creatinine (OH/Crt)] in adult female twins; 39 monozygotic (MZ) and 31 dizygotic (DZ) twin pairs (age, mean +/- SEM, MZ: 51.1 +/- 1.5 yrs; DZ: 46.5 +/- 1.5 yrs, P = NS). Of these subjects, 18 MZ twin pairs and 10 DZ twin pairs were postmenopausal. The MZ twin pair correlations (rMZ) for each index of bone turnover exceeded that between DZ pairs (rDZ), but this difference was only significant for osteocalcin (rMZ = 0.81, rDZ = 0.21, P less than 0.001). Similarly, in the postmenopausal group examined alone, the rMZ (r = 0.84) for serum osteocalcin was significantly greater than rDZ (r = -0.003, P less than 0.03). These osteocalcin data imply that 80% of the variance in serum osteocalcin could be explained by genetic factors. Although genetic effects on fasting urinary hydroxyproline:creatine and calcium:creatinine were not demonstrable, these indices may be less precise and specific. The data indicate that circulating osteocalcin, and therefore bone formation, is strongly genetically determined. These studies suggest at least one of the mechanisms of the genetic effect on bone mass relates to the regulation of bone turnover.

Adult↗

Dietary calcium, sex hormones, and bone mineral density in men.

OBJECTIVE: To evaluate the factors that determine bone mineral density at axial and appendicular sites in normal men. DESIGN: Measurement of bone mineral density of the radius by single photon absorptiometry and of the lumbar spine and hip by dual photon absorptiometry to assess their relation with various determinants of bone mineral density. Dietary calcium was assessed from a questionnaire validated against a four day dietary record. SETTING: Local community, Sydney, Australia. PATIENTS: 48 Men (aged 21-79, median 44) recruited from the local community including 35 male cotwins of twin pairs of differing sex recruited from the Australian National Health and Medical Research Council twin registry for epidemiological studies on determinants of bone mineral density. MAIN OUTCOME MEASURES: Bone mineral density of the axial and appendicular skeleton and its relation to age, anthropometric features, dietary calcium intake, and serum sex hormone concentrations. RESULTS: Dietary calcium intake (g/day) was a significant predictor of bone mineral density of axial bones, explaining 24% and 42% of the variance at the lumbar spine and femoral neck respectively. This effect was independent of weight. In contrast with the axial skeleton, bone mineral density at each forearm site was predicted by weight and an index of free testosterone but not by dietary calcium intake. CONCLUSIONS: Dietary calcium intake has a role in the determination or maintenance, or both, of the axial but not the appendicular skeleton in adult men.

Adult↗

Somatomedin-C, physical fitness, and bone density.

Somatomedin-C (Sm-C) or insulin-like growth factor-I, GH and physical fitness decline with age. Physical fitness and muscle strength are important determinants of bone density, and the age-related decline in bone density may be related in part to a decline in fitness and muscle strength. Also, Sm-C has been shown to stimulate osteoblasts in vitro and may effect skeletal muscle mass. We postulated that the age-related decline in GH and Sm-C levels may be related to an age-related decline in physical fitness and/or muscle strength, and the effect of physical fitness and muscle strength on bone may be mediated by Sm-C. We, therefore, examined the relationship between circulating GH and Sm-C levels and physical fitness, as determined by predicted maximal oxygen uptake (VO2max) in 134 normal women, 34 of whom were postmenopausal. In a subgroup of 62 women overall muscle strength was estimated as the sum of the Z-sores for biceps, quadriceps, and grip strength. Overall muscle strength correlated with GH levels (r = 0.28; P less than 0.02), but not with Sm-C levels. There was a significant positive relationship between plasma Sm-C levels and VO2max in all women (r = 0.47; P less than 0.001) and in the postmenopausal group alone (r = 0.05; P less than 0.01). Although there was a significant negative relationship between Sm-C and age (r = -0.36; P = 0.001), VO2max was a better independent predictor than age (r = 0.47; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of tobacco use on axial and appendicular bone mineral density.

Tobacco use has been identified as being a risk factor for the development of osteoporosis. While some data have suggested an effect on peripheral bone mass there are little previous data examining the role of tobacco use in axial skeletal bone loss. We examined tobacco use in relation to lumbar spine and proximal femur bone mineral density and forearm bone mineral content in 203 women. Data from identical twin pairs, comprising a subgroup of the larger group as well as a small number of male twin pairs, was also analyzed. The data show a difference in lumbar and proximal femur BMD of 0.03 and 0.06 g/cm2 respectively between smoking and nonsmoking identical twins. There was however no difference in the cross-sectional studies and no significant deleterious effect detected of tobacco use on forearm bone mineral content. The effect of smoking on lumbar and proximal femur bone mineral density, in identical twins discordant for tobacco use, was equivalent on average to 3 to 4 years of normal postmenopausal bone loss.

Bone Density↗

Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study.

Low dose corticosteroids are effective in suppressing synovitis in rheumatoid arthritis (RA), but there remains concern about their side effects, particularly osteoporosis. To examine the effects of low dose corticosteroids on bone loss in RA bone mineral density (BMD) was measured in the lumbar spine and hip for up to two years in 15 patients treated with these agents (mean dose prednis(ol)one 6.6 mg/day). 15 patients not receiving them, and 15 age matched controls. The initial BMD at both skeletal sites was significantly reduced in both patient groups compared with controls. The mean change in bone density was 0.2, 0.1, and -0.1% a year in the spine and -2.0, -1.9, and -1.0% a year in the hip respectively for the three groups. These rates of bone loss were not significantly different between groups at either site. These findings suggest that low dose corticosteroid treatment in RA is not associated with an increased risk of osteoporosis.

Arthritis, Rheumatoid↗

Age and menopause-related changes in indices of bone turnover.

Age-related bone loss has been attributed to a decline in bone formation due to decreased osteoblast function. However, studies examining the relationship between age or menopausal status and indices of bone formation such as serum osteocalcin have yielded conflicting results. To examine these relationships we studied indices of bone formation and resorption and bone mineral density in 247 normal women, including 96 postmenopausal women ranging in age from 20-75 yr. A cubic polynomial regression best fit the relationship between age and serum osteocalcin (r = 0.32; n = 228; P = 0.0001) and urinary hydroxyproline/creatinine excretion (r = 0.40; n = 228; P = 0.0001), with both indices declining before the menopause, rising at the menopause, and subsequently falling through the seventh and eighth decades. While a significant decline in osteocalcin levels was observed in the postmenopausal group older than 60 yr, levels in subjects older than 60 yr remained higher (+31%) than those in late premenopausal subjects. Urinary calcium to creatinine excretion rose in the premenopausal years, increased markedly after the menopause, and remained at this level subsequently. Urinary hydroxyproline/creatinine, but not serum osteocalcin or urinary calcium/creatinine excretion, was a significant predictor of bone mineral density at the lumbar spine and the femoral neck independent of age. These data are consistent with the hypothesis that age-related bone loss after the menopause occurs in the presence of initially increased but subsequently decreasing bone turnover with maintenance of a relative excess of bone resorption.

Adult↗

A simple method for assessing calcium intake in Caucasian women.

Calcium intake has been implicated in the etiology of age-related osteoporosis. There is evidence to suggest that many postmenopausal women consume inadequate calcium to maintain calcium balance. One of the most accurate methods of calculating dietary intake is the weighed food record; however, that method is time consuming and unsuitable for large numbers of individuals. To determine the adequacy of calcium intake in the large numbers of postmenopausal women at risk of osteoporosis, simpler methods of assessing calcium intake are required. We therefore developed a food frequency questionnaire and tested it against a 4-day weighed food record in 54 Caucasian women, between 29 and 72 years of age. Twenty-six of the women (Group 1) completed a 4-day record and questionnaire within 1 week. Another 28 women (Group 2) completed the questionnaire 1 to 12 months after completing the 4-day food diary. A good correlation (r = .79, p less than .001) was found between the two methods of calculating calcium intake for the 54 women. Independent analysis of Group 1 and Group 2 showed correlation coefficients of 0.81 and 0.78, respectively. The correlation for postmenopausal women (r = .84) was similar to that of premenopausal women (r = .79). The data show that a short, simple questionnaire can be used to rank individuals according to adequacy of calcium intake as a prerequisite to nutrition intervention.

Adult↗

Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis.

Sex hormones have important effects on bone, especially in postmenopausal women. These hormones may be of particular significance in patients with rheumatoid arthritis (RA), who have a high frequency of osteoporosis. To examine this, we measured estrogen and androgen concentrations and bone mineral density (BMD) in 49 postmenopausal women with RA and 49 normal postmenopausal women. Compared with the controls, postmenopausal RA patients had significantly reduced levels of estrone (median 18 pmoles/liter versus 49; P less than 0.001), dehydroepiandosterone sulfate (DHEAS) (median 0.3 mumoles/liter versus 2.0; P less than 0.001), testosterone (median 0.6 nmoles/liter versus 0.95; P less than 0.001), and femoral BMD (mean 0.72 gm/cm2 versus 0.80; P less than 0.002). Prednisolone therapy in 22 patients (mean dosage 8 mg/day) was associated with reductions in estrone and testosterone levels; however, DHEAS and femoral BMD were also decreased in RA patients who were not receiving corticosteroids. Reduced DHEAS levels in postmenopausal women with RA may increase their risk of osteoporosis.

Arthritis, Rheumatoid↗

Bone mineral density in Australia compared with the United States.

Bone density measurements are currently being performed throughout the world in the diagnosis and management of osteoporosis as well as in research into this major health problem. However, it is not clear to what extent bone mineral density (BMD) values determined by dual-photon absorptiometry at one center can be applied to another. This is particularly relevant for the quantitative comparison of results from studies carried out in different laboratories. Furthermore, many centers now acquiring densitometers may not have the resources to determine their own normal range, relying instead on a "normal" range provided by the manufacturer. The question of the comparability of BMD data obtained in different centers was examined by comparing the normal range for the lumbar spine and proximal femur in 203 normal white Australian women and 892 normal white U.S. women, obtained using the same model densitometer. The two populations were compared according to decade. From superimposition of the Australian individual values on the North American normal ranges, only minor differences between the two populations were seen at any of the sites measured at any decade. None of these minor differences were statistically significant. This study shows a close similarity between BMD values in both the proximal femur and lumbar spine in normal white women in Australia and North America, provided the same model densitometer is used. Thus data obtained from different centers in populations with similar ethnic composition may be compared directly. These findings provide for the first time a sound basis for the quantitative comparison of the at times conflicting studies carried out in widely differing settings around the world.

Adult↗

Serum insulin and bone density in normal subjects.

A relationship between circulating insulin and bone mass has been postulated. To test this hypothesis we measured fasting serum insulin and quantitated bone density in the forearm, spine and femoral neck by single and dual photon absorptiometry of 70 normal women. There was no statistically significant relationship between insulin and bone density at any site by correlation or regression analysis. Although the relationship between a single measurement of a hormone (at one point in time) and bone density (the result of lifelong factors) should be interpreted with caution, our findings do not support the hypothesis that there is an association between serum insulin and bone mass.

Adult↗

Dietary intake and bone mineral density.

Osteoporosis, a major health problem in all Western countries, is a condition in which many dietary factors have been implicated. To determine the influence of diet on bone mass in the proximal femur, the intake of 14 nutrients was measured in 159 Caucasian women, aged 23-75 years and bone mineral density (BMD) quantitated in the hip by dual photon absorptiometry. BMD was also measured in the spine and bone mineral content (BMC) in the forearm by single photon absorptiometry. No significant correlation was found between current calcium intake and bone mass at any site. Iron was a positive predictor of BMD in the femoral neck and alcohol intake a positive predictor of BMD in the trochanteric region of the proximal femur in premenopausal women by multiple regression analysis. Iron, zinc and magnesium intake were positively correlated with forearm BMC in premenopausal women. Iron and magnesium were significant predictors of forearm BMC in premenopausal and postmenopausal women respectively by multiple regression analysis. These results suggest that bone mass is influenced by dietary factors other than calcium.

Adult↗

Nutritional intake of pre- and postmenopausal Australian women with special reference to calcium.

Dietary factors, in particular calcium intake, have been implicated as risk factors in the aetiology of osteoporosis. In Australia there are few published data on the calcium intake of either premenopausal or postmenopausal women. The dietary intakes of calcium and 14 other nutrients were measured in 82 premenopausal and in 65 postmenopausal Caucasian women aged between 23 and 75 years. We found that 75 per cent of the postmenopausal and 61 per cent of the premenopausal women failed to meet the Australian recommended dietary allowance (RDA) for calcium of 1000 mg and 800 mg/d respectively. Moreover, 29 per cent of the postmenopausal women consumed less than 500 mg/d of calcium. Other nutrients including zinc, magnesium and iron were also deficient for many subjects. These data are relevant to the evaluation of dietary factors in the aetiology of osteoporosis.

Adult↗

Dual-photon bone densitometry in normal Australian women: a cross-sectional study.

Osteoporosis is a major health problem in Australia, as it is in most Western societies. Bone mineral density in the spine and femoral neck are accurate indicators of osteopenia and thus useful indicators of the risk of a fracture. Dual-photon absorptiometry is a non-invasive technique that allows the accurate quantitation of bone mineral density in the lumbar vertebrae and proximal femur with a low radiation exposure. The increasing availability of this technique dictates the requirement for "normal" ranges and quality control. We report here lumbar vertebral and proximal femur bone mineral density as measured by dual-photon absorptiometry in 179 normal Australian women. Forearm bone mineral content in these subjects, as measured by single-photon absorptiometry, is also presented. There was a relative stability of lumbar bone mineral density and forearm bone mineral content before the menopause, after which there was an age-related decline. On the other hand, bone mineral density at all three sites in the proximal femur showed an age-related decline throughout adult life. Intraoperator variability in calculated bone mineral density did not exceed 2.3%. The requirement for correct positioning of the patient is illustrated. The data allow statistical analysis and the development of normal ranges. They provide an Australian base against which individual patient values can now be compared.

Adult↗

Determinants of axial bone loss in rheumatoid arthritis.

To assess mechanisms that cause generalized osteoporosis in rheumatoid arthritis (RA), we measured bone mineral density (BMD) by dual photon absorptiometry in the lumbar spine and femoral neck of 111 patients with RA. BMD was significantly reduced at both sites in these patients. Physical activity correlated significantly with BMD in patients with RA, and was found, by multiple regression analysis, to be a significant predictor of femoral bone density in female patients. Multiparity exerted a protective effect on lumbar bone density. Prednisolone (mean dosage 8 mg/day) was not associated with significantly increased bone loss in women, whereas higher dosages in men (mean 10.3 mg/day) were associated with increased lumbar bone loss. Reduced physical activity leading to a form of disuse osteoporosis appears to be an important factor in axial bone loss in RA.

Aged↗

Computer modeling and analysis of cross-sectional bone density studies with respect to age and the menopause.

Controversy exists about rates of bone mineral loss from the lumbar spine at the menopause. Cross-sectional studies of lumbar bone mineral against age have been interpreted as evidence for or against a menopause-related change in lumbar bone loss, depending on their goodness of fit to either linear or nonlinear equations. To investigate the ability of cross-sectional studies to detect accelerated lumbar bone loss at the menopause, we constructed models of different patterns of loss and evaluated the findings in cross-sectional analyses of computer-simulated populations of normal women. A sample size of greater than 300 was needed to distinguish between linear and nonlinear patterns of bone loss with a power of 90% when the data was analyzed throughout life. Examining for differences between the slopes of the regressions of pre- and postmenopausal women was more useful for detecting nonlinear bone loss under some circumstances. A difference between slopes was apparent in studies containing 100 subjects if lumbar bone density (BMD) was assumed to be unchanged prior to the menopause, but a larger study size was needed (greater than 1000) if BMD was assumed to fall before the menopause. We also measured lumbar BMD by dual photon absorptiometry in 141 normal females. When the data was analyzed against age throughout life, a nonlinear pattern of bone loss was found, and comparison of pre- and postmenopausal subjects showed a significant difference in the slopes of the linear regressions. Our patient data support the concept of a relatively stable lumbar BMD prior to the menopause with a rapid but transient decline postmenopausally.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Genetic determinants of bone mass in adults. A twin study.

The relative importance of genetic factors in determining bone mass in different parts of the skeleton is poorly understood. Lumbar spine and proximal femur bone mineral density and forearm bone mineral content were measured by photon absorptiometry in 38 monozygotic and 27 dizygotic twin pairs. Bone mineral density was significantly more highly correlated in monozygotic than in dizygotic twins for the spine and proximal femur and in the forearm of premenopausal twin pairs, which is consistent with significant genetic contributions to bone mass at all these sites. The lesser genetic contribution to proximal femur and distal forearm bone mass compared with the spine suggests that environmental factors are of greater importance in the aetiology of osteopenia of the hip and wrist. This is the first demonstration of a genetic contribution to bone mass of the spine and proximal femur in adults and confirms similar findings of the forearm. Furthermore, bivariate analysis suggested that a single gene or set of genes determines bone mass at all sites.

Adult↗

Recovery from steroid-induced osteoporosis.

The reversibility of steroid-induced osteoporosis, a major complication of Cushing syndrome and long-term use of exogenous corticosteroids, is not well documented. We measured the bone mineral density of lumbar vertebras and the femoral neck by dual-photon absorptiometry and determined the biochemical variables of bone turnover in two patients successfully treated for Cushing syndrome who were followed for the next 24 months. Our data are the first to show marked increases in bone density (up to 20%) during the recovery period. The accompanying biochemical changes, particularly the marked increase in serum osteocalcin levels, confirm that enhanced bone formation occurred during the recovery phase. These findings suggest that steroid-induced osteoporosis can be reversed at least in young persons.

Adrenalectomy↗

Limitations of forearm bone densitometry as an index of vertebral or femoral neck osteopenia.

Osteoporosis of the spine and femoral neck is a major problem in aging populations, but detection prior to a fracture remains a challenge. Forearm bone mineral content has been advocated as a useful screening test in this situation. We have examined the correlation between distal forearm bone mineral content, by single photon absorptiometry, and lumbar vertebral and femoral neck bone mineral density, by dual photon absorptiometry. Eighty women aged 20 to 76 years were studied and significant correlations (p less than .001) were found between the measurements on the forearm and at the two axial sites (r = 0.66 and 0.69, respectively). However, forearm bone mineral content was an unreliable predictor of axial bone mineral density. For prediction of lumbar spine osteopenia with a sensitivity of 88%, the false positive rate was 91%. Conversely, to achieve a specificity of 82%, the false negative rate was 65%. Similarly, for prediction of femoral neck osteopenia at a sensitivity of 92%, the false positive rate was 87%, and at a specificity of 90%, the false negative rate was 33%. These data demonstrate that forearm bone densitometry cannot be used as a screening procedure for osteopenia of the lumbar spine or femoral neck.

Adult↗