Dependence and oestrogen replacement.
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Biomedical subjects
Publications and source records attributed to J E Compston.
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Using a computerised technique, resorption cavity characteristics in iliac crest trabecular bone were assessed in 30 patients with chronic renal failure and compared with data obtained from healthy subjects. The mean and maximum cavity depth were significantly greater in the patient group (P less than 0.0001); in addition, cavity area, the percentage of bone being remodelled, the number of cavities per mm trabecular surface and the percentage eroded surface were all significantly greater than in controls (P less than 0.0001). However, the surface length of individual cavities in the patient group did not differ significantly from that of controls. In the patient group, serum intact parathyroid hormone concentrations showed a significant positive correlation with mean resorption cavity depth (r = 0.451, P less than 0.05). Our results demonstrate that the increase in bone resorption associated with hyperparathyroidism secondary to chronic renal failure is due to an increase both in the number and depth of cavities, although the surface extent of individual cavities is normal. These findings indicate that factors determining the length of trabecular surface eroded and the depth of individual resorption cavities are controlled by different mechanisms.
Manual methods for the measurement of bone biopsies have largely been superseded by semi-automatic computerised techniques. Histomorphometrists often use control data obtained by other observers using different methods, thus combining inter-observer and inter-method variation. We have examined the combined effect of inter-method and inter-observer variation on measurements of bone area, osteoid perimeter, and osteoid width in iliac crest biopsies from healthy subjects, one observer using the manual grid system and the other using a semi-automated technique. Inter-observer and inter-method variation were independently determined, and the proportion of each expressed as a percentage of combined error. Our results indicate that the combination of inter-method and inter-observer variation causes significant differences in the values obtained for osteoid perimeter, whereas inter-method variation is mainly responsible for differences in osteoid width values; differences in bone area are largely due to inherent sampling variation. These variations indicate that caution is required when comparison is made with control data from other sources, especially if different techniques are employed.
1. Total body areal bone mineral density was measured by dual-energy X-ray absorptiometry in eight women before and 10 weeks after a very-low-calorie diet [405 kcal (1701 kJ)/day]. 2. The mean weight loss of 15.6 kg was accompanied by a statistically significant reduction in total body bone mineral density from 1.205 +/- 0.056 to 1.175 +/- 0.058 g/cm2 (mean +/- SD, P less than 0.005). 3. After cessation of the diet, weight gradually increased and by 10 months was similar to baseline values. Total body bone mineral density also increased after stopping the diet and mean values obtained 10 months after the diet did not differ significantly from initial values. Throughout the study total body bone mineral density values in all subjects were well within the range reported for normal subjects. 4. These data indicate that diet-induced weight loss is associated with rapid bone loss, subsequent weight gain being accompanied by increases in bone mass. Further studies are required to establish the clinical significance of these findings and, in particular, the skeletal distribution of bone loss.
Osteoporosis is characterised by low bone mass, leading to an increased risk of fragility fracture, particularly in the femoral neck, vertebrae and radius. These fractures constitute a major public health problem in the Western world; the estimated annual cost to the health services of hip fracture alone is over 500 million pounds in the United Kingdom. Using population-based data from the USA, Cummings et al. have estimated that the lifetime risks of hip, vertebral and Colles' fractures in a 50 year old, white, postmenopausal woman are 16%, 32% and 15% respectively. Of these, vertebral fractures probably cause the most significant morbidity, since they occur at a younger age than hip fractures and may result in pain, deformity and disability for many years until death intervenes from other causes. Hip fractures occur most commonly in the eight and ninth decades of life and have a mortality at six months of around 15%, increased dependency occurring in the majority of survivors. Colles' fractures, although not usually associated with long-term morbidity, nevertheless cause considerable inconvenience and require hospital treatment.
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OBJECTIVE: We aimed to assess total body composition and to study the interrelationships between fat and lean tissue mass with total and regional bone mass in healthy British post-menopausal women. DESIGN AND PATIENTS: Total body composition and regional bone mass were measured in 97 healthy post-menopausal women recruited from the general community. The mean age was 57.9 years, range 49-65. MEASUREMENTS: Total body composition (fat, lean tissue and bone mineral) and regional bone density in the lumbar spine and femur were measured by dual energy X-ray absorptiometry on a Lunar DPX. RESULTS: Significant negative correlations with age were found for total body bone mineral density (r = -0.200, P = 0.049), and lumbar spine bone mineral density (r = -0.28, P = 0.006); the calculated rate of bone loss from these two sites was 0.33 and 0.7% per annum respectively. Fat tissue mass showed a positive correlation with age (r = 0.22, P = 0.03). High correlations were observed between total body and regional bone mineral density (r = 0.755-0.829, P < 0.001). After adjustment for age and lean mass, statistically significant correlations were seen between fat tissue mass and all bone mass measurements (P < 0.01-0.001), the strongest correlations being found for total body bone mineral content and density (r = 0.477 and 0.488 respectively). Lean tissue mass showed a strong correlation with total body bone mineral content (r = 0.580, P < 0.001), after adjustment for age and fat mass; it was less strongly correlated with other bone mass measurements than fat mass, showing only weak correlations with total body, trochanteric and lumbar spine bone mineral density (r = 0.228-0.246, P < 0.05). Age-adjusted body weight showed stronger correlations with total and regional bone mass than did either body mass index or height. CONCLUSIONS: Both fat and lean tissue mass are related to total and regional bone mass in post-menopausal women, the relationship being strongest for fat mass. Body weight shows stronger correlations with bone mass than either height or body mass index. In view of the direction and magnitude of changes in fat, lean tissue and bone mineral after the menopause, adiposity and muscularity are more likely to be determinants of peak bone mass than of the rate of post-menopausal bone loss.
The presence of normal bone density values in the lumbar spine is often assumed to exclude osteoporosis. Eleven cases are reported in which normal lumbar spine bone density and radiology were associated with one or more dorsal spine fractures; the diagnosis was postmenopausal osteoporosis in eight patients and corticosteroid induced osteoporosis in three. These findings suggest that spinal osteoporosis may sometimes be a focal disorder and emphasise the need for dorsal spine radiology in addition to bone densitometry in patients with strong risk factors for osteoporosis or with clinical evidence of the dorsal spine being affected.
In order to describe the relationships between endogenous sex hormones and bone mineral density in healthy postmenopausal women, we carried out a cross-sectional study of 90 community-based women, all at least one year since their last menstrual period (mean 9.6 +/- 4.9 years, range 1-22) and with a serum oestradiol level less than 100 pmol/l. None was currently using hormone replacement therapy. Serum oestradiol, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate, and androstenedione were measured using standard techniques. Free oestradiol and testosterone indices were derived as the ratio of total hormone to sex hormone binding globulin, respectively. Total body, spine and hip bone mineral density (g/cm2) were measured by dual energy X-ray absorptiometry. Significant positive correlations were found between the free oestradiol and testosterone indices and bone mineral density at all sites. These relationships remained significant for the free oestradiol index after adjustment for age and body mass index. By stepwise multiple regression analysis, the free oestradiol index was an independent predictor of total body, spine and hip bone mineral density, accounting for 4-17% of the variance. These findings suggest an independent positive relationship between endogenous free oestradiol and total body, spine and hip bone mass even in the late postmenopause.
We have investigated whether the Lunar DPX (software 3.4) and Hologic QDR-1000 dual-energy X-ray absorptiometers have comparable normal reference databases for the spine and femur of white UK and USA subjects. After conversion for systematic differences in absolute bone density values between the two systems, the reference databases were very similar for the spine in young subjects, but there were clear differences in the femur databases of young females and males of all ages. These differences were confirmed by comparing the percent age-matched and young values determined by the two systems for subjects scanned on both systems. Thus the diagnosis and management of a patient could differ, depending on the system used for the bone density measurements.
Bone mineral density of the radius was measured by single-photon absorptiometry in 50 patients with inflammatory bowel disease. Thirty-three had Crohn's disease and 17 ulcerative colitis; 25 were women. The mean age was 45 years (range, 18-70 years). Measurements were repeated in 39 of them after a mean follow-up period of 7.9 years (range, 7.1-8.2 years). In female patients the mean (95% confidence interval) annual change in radial bone mineral density was -0.74% (-1.34% to -0.14%) (P = 0.022), the greatest bone loss occurring in postmenopausal women (mean, -1.16% (-2.01% to -0.30%)). In male patients the mean annual rate of bone loss was -0.07% (-0.41% to 0.28%) (P = NS). Patients with abnormally low values at the first measurement remained osteopenic at the second measurement, whilst some others with normal values initially showed increased rates of bone loss and had a subnormal bone mineral density after the follow-up period. These results show increased rates of cortical bone loss in some patients with inflammatory bowel disease and emphasize the need to monitor bone mass in these patients so that prophylactic measures can be instituted.
The depth of resorption cavities in trabecular bone is an important determinant of bone structure and has implications relevant to the cellular pathophysiology of bone loss in osteoporosis. However, assessment of resorption depth has proved difficult and few data are available; in this study we report age-related changes in iliac crest trabecular bone obtained from 41 normal healthy subjects (21 female, 20 male) aged 22-80 years. Using 8-microns undecalcified sections stained with toluidine blue, resorption cavities were quantitatively assessed by a computerized technique in which the eroded bone surface is reconstructed and measurements made interactively. Maximum and mean cavity depth showed no significant correlation with age in either sex. The absolute length of eroded surface was unrelated to age but the eroded surface/BS (%) and the number of cavities/BS (/mm) showed a significant positive correlation with age (r = 0.384 and 0.386 respectively, p less than 0.05). No significant correlation was found between age and either cavity area or density. These results suggest that increased resorption depth does not contribute to age-related bone loss, although the possibility that deeper resorption cavities occur which result in trabecular penetration and are therefore unrecognizable cannot be discounted. The age-related increase in eroded surface/BS (%) reflects a decreased available trabecular surface and/or increased number of cavities rather than a greater surface length of individual cavities; alternatively it may indicate an increased resorption period. No evidence of increased resorption depth at the time of the menopause was found in this study.
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1. Serial measurements of total body calcium have been made by prompt gamma-neutron activation analysis in 13 patients with inflammatory bowel disease over a mean period of 23 months. Changes in spinal trabecular bone mineral density and radial shaft bone mineral content were also assessed by using quantitative computed tomography and single photon absorptiometry, respectively. 2. The mean annual decreases (95% confidence intervals) were: total body calcium, 7.8% (-12.0 to -3.7%; P less than 0.001); spinal trabecular bone mineral density, 2.5% (-5.0 to +0.1%; 0.05 less than P less than 0.1), radial bone mineral content, 2.1% (-3.4 to -0.8%; P less than 0.01). 3. No significant correlations were found between rates of change of the three variables. However, there were significant positive correlations between the baseline values for total body calcium and radial bone mineral content (r = 0.638, P less than 0.05), spinal bone mineral density and radial bone mineral content (r = 0.854, P less than 0.01), and total body calcium and spinal bone mineral density (r = 0.876, P less than 0.001). 4. These results demonstrate rapid decreases in total body calcium in patients with inflammatory bowel disease which, in conjunction with the significant decrease in radial shaft bone mineral content, indicate increased rates of cortical bone loss. Whilst values for bone mass at different skeletal sites showed positive correlations within individuals, no relationship was found between the rates of change in bone mass at these sites. 5. The rapid bone loss observed in some subjects emphasizes the importance of early detection of osteoporosis by bone densitometry and the need for effective prophylactic measures to be established in this group of patients.
In order to establish the prevalence of osteomalacia in elderly patients with hip fracture, trans-iliac biopsies were obtained from 49 patients, aged 67-92 years, admitted to Cardiff Royal Infirmary with hip fracture. Undecalcified sections were quantitatively assessed and the diagnosis of osteomalacia was made when there was an increase in mean osteoid seam width (greater than 15 microns) associated with a reduction in calcification fronts (less than 60% of osteoid-covered surfaces). Osteomalacia was present in only one patient; in the remaining patients, osteoid surface extent, volume and mean seam width were within normal limits. Thus osteomalacia, when defined by rigorous histomorphometric criteria, was rare in these elderly subjects with hip fracture.
The measured absolute bone mineral density values of spine and femur and their precision were compared on two dual energy X-ray absorptiometers, the Lunar DPX and the Hologic QDR-1000. There were systematic differences between the two systems, the Lunar DPX always giving a higher bone density value. The ratio of the mean Lunar DPX/Hologic QDR-1000 bone density measurements obtained in vivo was 1.13 g/cm2 for spine (L2-L4) and 1.20-1.43 g/cm2 for femur measurements. For both systems, short- and long-term precision (coefficient of variation) was below 0.5% for spine in vitro measurements and below 1.5% for neck of femur in vitro measurements. Precision of in vivo measurements was less good, especially for femur measurements. The coefficient of variation of spine measurements was dependent on bone density and deteriorated with decreased bone mineral density and increased body thickness.
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