Broadband ultrasonic attenuation and bone mineral density.
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Bone and Bones↗
Biomedical subjects
J E Compston
Publications and source records attributed to J E Compston.
Spinal trabecular bone mineral content in patients with non-steroid treated rheumatoid arthritis.
Spinal trabecular bone mineral content was measured in the first, second, and third lumbar vertebrae by quantitative computed tomography in 88 patients with non-steroid treated rheumatoid arthritis. Results were compared with those obtained in 105 healthy control subjects. The mean bone mineral content in the patient group, 135.8 (SD 32.8) mg/ml K2HOP4, was significantly lower than that in the controls (151.9 (32.1) mg/ml, p less than 0.01). Division of patients and controls into three age groups showed that the reduction in bone mineral content was most marked in the youngest age group (21-40 years), the mean value in male patients being significantly lower than in controls (149.6 (51.3) v 171.7 (23.9) mg/ml K2HPO4, p less than 0.05); in female patients in this age group the corresponding values were 160 (26.1) v 178.4 (22.0) mg/ml, 0.05 less than p less than 0.1). No significant difference in mean values between patients and controls was found in the other age groups. Of the 88 patients, six (7%) had abnormally low values, defined as a bone mineral content greater than 2 SD below the normal mean. One vertebral crush fracture was found in one patient but not in any of the controls. No correlation was found between bone mineral content and body weight, duration of disease, or disability as assessed by the London and Steinbroker methods. These results demonstrate a lower spinal trabecular bone mineral content in non-steroid treated patients with rheumatoid arthritis than in age and sex matched controls, the difference being most marked in younger patients. The finding of abnormally low values in 7% of the patients indicates a slightly increased prevalence of spinal osteoporosis in these patients.
Adult↗
Increased rate of spinal trabecular bone loss in patients with inflammatory bowel disease.
The rate of spinal trabecular bone loss during one year was measured in 54 patients with inflammatory bowel disease. The mean change in spinal bone mineral content was -5.1 mg/ml K2HPO4, representing 3% of the initial bone mineral content. The rate of bone loss showed a significant negative correlation with body mass index (r = -0.276, p less than 0.05) but no other significant correlations were found with other clinical or biochemical indices, including the total amount of prednisolone taken during the course of the study. Eleven patients had bone loss greater than 15 mg/ml/year; these included four non-steroid treated patients, two of whom had disease confined to the large bowel. The results indicate rapid rates of bone loss in some patients with inflammatory bowel disease over the course of one year. Although steroid therapy and malnutrition are likely to be contributory factors in some patients, other, as yet unidentified, risk factors also operate. The rapid bone loss observed in some patients emphasises the need for effective prophylactic regimes.
Adult↗
Bone histomorphometry and structure in corticosteroid treated chronic active hepatitis.
Transiliac biopsies from 34 female patients with corticosteroid treated chronic active hepatitis have been examined to determine the contributions made by decreased bone formation and increased bone resorption to bone loss associated with this condition and to determine the structural basis of the bone loss. Mean wall thickness was significantly reduced when compared with control values (p less than 0.001) as was the bone formation rate at tissue (p less than 0.005) and basic multicellular unit (p less than 0.005) level. The osteoid maturation period and the bone formation period were significantly prolonged (p less than 0.02 and 0.05). The total resorption surfaces were significantly increased (p less than 0.02) but the mean interstitial bone thickness was normal. The mean trabecular plate thickness was significantly reduced (p less than 0.005). These findings indicate that decreased bone formation plays a major role in bone loss associated with corticosteroid treated chronic active hepatitis and that the structural basis of bone loss is trabecular thinning.
Adult↗
Bone mineral content in normal UK subjects.
Bone mineral content in the lumbar vertebrae and in the shaft of the left radius has been measured in 129 normal British subjects using quantitative computed tomography and single-photon absorptiometry. Significant negative correlations between bone mineral content and age were found at both sites in males and females (p less than 0.001 in all cases). When expressed in g/cm the bone mineral content in the radial shaft showed significant positive correlations with body height and weight in both sexes, but after correction for bone size only a weak correlation with body height in males was found. Spinal trabecular bone mineral content showed no significant correlations with body height or weight in either sex. Comparison of the values obtained with normal data from centres in the USA revealed lower mean values for both radial and spinal bone mineral content in the British subjects. These differences emphasize the importance of using locally derived normal data for comparison with values obtained from patients.
Adolescent↗
Age-related changes in iliac crest trabecular microanatomic bone structure in man.
Age-related changes in the microanatomic structure of human iliac crest trabecular bone have been investigated in biopsies from 90 subjects, using a new computerised method which automatically identifies and quantifies nodes, free ends and a number of topologically defined struts. In both sexes there was a significant age-related decrease in the number of nodes and of trabecular struts, corrected for section area. In females, there was also a significant age-related decrease in the node to free end ratio (P less than 0.001), and the combined node-to-node and node-to-loop strut length, expressed as a percentage of total strut length (P less than 0.001) and a significant increase in free end to free end strut length (P less than 0.001). In males, the only additional age-related change was a significant increase in the cortex to free end strut length (P less than 0.005). These results indicate that loss of trabeculae resulting in decreased interconnectedness of the normal trabecular bone structural pattern, plays an important role in age-related bone loss in females. Removal of trabeculae also occurs in males but in less prominent, implying that trabecular thinning makes a greater contribution to age-related bone loss in males.
Adult↗
Measurement of mean trabecular plate thickness by a new computerized method.
Mean trabecular plate thickness (MTPT) has been measured by a new direct computerised method on an IBAS II image analyser in iliac crest bone from 56 normal subjects. The new method has been shown to be accurate and reproducible; apart from some initial editing of the image, it is carried out automatically without any need for observer interaction. A close correlation was found between values for MTPT obtained using the new direct method and values obtained by calculation based on area and perimeter measurements made on the IBAS II (r = 0.98).
Adult↗
Iliac crest trabecular bone mass and structure in patients with non-steroid treated rheumatoid arthritis.
Iliac crest trabecular bone volume and structure have been studied in bone biopsy specimens from 48 patients with classical or definite rheumatoid arthritis, none of whom had received steroids. Results were compared with those obtained from healthy controls matched for age and sex. The mean trabecular bone volume in female patients aged 34-50 years was significantly lower than in controls (p less than 0.01); in male patients aged 34-50 years values were also lower than those in controls (mean (SD) 17.8 (3.2) v 22.4 (5.6)% total medullary volume), though this difference was not statistically significant. Values in older patients were similar to those of controls. The mean trabecular plate thickness was significantly lower in female patients in all three age groups when compared with the controls (p less than 0.005, 0.05, and 0.005). Similar but non-significant changes were seen in male patients. The mean trabecular plate density, an index of trabecular number, and the mean trabecular plate separation showed no age related change in either male or female patients, in contrast with the female control group, in whom the mean trabecular plate density decreased and separation increased with age. These results suggest that non-steroid treated rheumatoid arthritis is associated with premature bone loss, the structural basis of which is trabecular thinning.
Adult↗
Osteoporosis in patients with inflammatory bowel disease.
Bone mineral content in spinal trabecular and peripheral cortical bone was measured in 75 unselected patients with small and/or large intestinal inflammatory bowel disease. Osteoporosis, defined as a bone mineral content greater than 2 SD below the age and sex matched normal mean value was present in 23 patients (30.6%). Three amenorrhoeic females aged 34, 38, and 42 years had severe clinical osteoporosis and a further three patients had one or more vertebral crush fractures. Eighteen of the 23 patients with osteoporosis had small intestinal disease with one or more resections and the mean lifetime steroid dose in those with osteoporosis was significantly higher than in those with normal bone mineral content. Bone mineral content in spinal trabecular bone showed significant negative correlations with lifetime steroid dose and serum alkaline phosphatase and a significant positive correlation with serum albumin. Peripheral cortical bone mineral content was positively correlated with body weight, height and body mass index. We conclude that the prevalence of osteoporosis is increased in patients with inflammatory bowel disease, severe clinical osteoporosis developing in some relatively young patients. The pathogenesis of this bone loss is probably multifactorial; steroid therapy is likely to be an important contributory factor.
Adult↗
Biliary excretion of radioactivity after intravenous administration of [3H]25-hydroxyvitamin D3 in man.
The biliary excretion of radioactivity after intravenous [3H]25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than [3H]25-hydroxyvitamin D3. No free [3H]25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following [3H]25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.
Adult↗
Inter-observer and intra-observer variation in bone histomorphometry.
Inter-observer variation has been examined for a number of histomorphometric indices in 20 normal human iliac crest biopsies. Quantitation was performed using an eye-piece graticule and eye-piece micrometer. The same sections were examined by two observers and the methodology was identical. Intra-observer variation was also assessed. Significant inter-observer differences were found for the measurement of total trabecular bone volume, osteoid volume and surface, double plus single and double tetracycline labeled surfaces, and the mean osteoid seam width. The percentage variance due to inter-observer variation was highest for osteoid surface and volume, total resorption surface, and mean osteoid seam width. Intra-observer variation in both observers was small. We conclude that a large inter-observer variation may occur in the measurement of a number of histomorphometric indices, even when section preparation and methodology are identical. Caution should be used in basing the diagnosis of metabolic bone disease on strictly defined control data from other observers, particularly when this has been obtained from centers where the effects of inter-observer variation may be magnified by differences in methodology.
Bone Resorption↗
A new method for the two-dimensional analysis of bone structure in human iliac crest biopsies.
A new method is described for the analysis of the two-dimensional structural pattern of trabecular bone in human iliac crest biopsies. 8 microns thick undecalcified sections stained with the von Kossa technique were examined at a magnification of X 9. Using an Ibas II image analyser, the ratio of nodes to free ends and the length of different strut types (cortex to free end, node or cortex, free end to free end and node to node, loop or free end) expressed as a percentage of total strut length were assessed. The reproducibility of the method was good for most of the measured indices but inter-observer and inter-section variation were greater. Comparison of biopsy sections obtained from eleven young healthy control subjects and eleven patients with hepatic osteoporosis revealed a significantly higher node to free end ratio, node to loop and node to node strut length and significantly lower cortex to free end and free end to free end strut length in the controls. No significant differences were seen in node to free end, cortex to cortex or cortex to node strut length. This approach to trabecular bone structure analysis should prove useful in determining patterns of bone loss in health and disease and in examining the effects of treatment on bone structure in osteoporosis.
Adult↗
Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease.
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Cholestasis↗
Intestinal calcium absorption in patients after jejuno-ileal bypass or small intestinal resection and the effect of vitamin D.
A forearm counter and double-isotope technique were used to measure intestinal calcium absorption in 21 patients after jejuno-ileal bypass for obesity or small intestinal resection. In all but 2 patients calcium absorption was below the normal range for 10 male controls. 3 weeks treatment with 1-alpha-hydroxyvitamin D, 1 microgram b.d., or 1,25-dihydroxyvitamin D, 1 microgram b.d., was associated with significant increases in absorption whereas 3 weeks treatment with 24,25-dihydroxyvitamin D had no effect. This study demonstrates that oral 1,25-dihydroxyvitamin D or 1-alpha-hydroxyvitamin D are effective in increasing calcium absorption.
24,25-Dihydroxyvitamin D 3↗
Relationship between toluidine blue-stained calcification fronts and tetracycline-labeled surfaces in normal human iliac crest biopsies.
The relationship between toluidine blue-stained calcification fronts and tetracycline labeling was examined in iliac crest biopsies from 56 normal subjects aged 19-80 years, all of whom had received double tetracycline labeling. Sections were quantitated using an eye-piece graticule and all values were expressed as a percentage of osteoid surface. Values for double plus single tetracycline-labeled surfaces were lower than those obtained for toluidine blue-stained calcification fronts in 66% of subjects, although the difference between the two measurements was not statistically significant. Values obtained for calcification fronts demonstrated by toluidine blue staining were significantly greater than those obtained for single, double, and double plus half single tetracycline-labeled surfaces. No significant correlation could be demonstrated between toluidine blue-stained calcification and tetracycline-labeled surfaces. In conclusion, the fraction of osteoid bearing a tetracycline label differed from that showing a toluidine blue-stained calcification front and no correlation could be demonstrated between the two measurements. These differences may arise from methodological problems associated with their demonstration and identification; alternatively their lack of similarity might reflect uptake of stain and tetracycline at different sites within the calcification front. Which of the two parameters most accurately represents the active mineralizing surface is unknown.
Adult↗
Biliary excretion of radioactivity after intravenous administration of 3H-1,25-dihydroxyvitamin D3 in man.
Biliary radioactivity excretion was studied in 10 patients with postcholecystectomy T-tube drainage after intravenous administration of 3H-1,25-dihydroxyvitamin D3. The mean +/- SD radioactivity excreted in T-tube bile expressed as a percentage of the administered dose was 18.9 +/- 10.7% per 24 hours. After correction for incomplete bile collection the value obtained was 28.8 +/- 12.8%. The mean chloroform solubility of the biliary radioactivity increased from 17.0 +/- 8.4% to 69.4 +/- 15.1% after incubation with beta-glucuronidase. High performance liquid chromatography of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than 1,25(OH)2D3. The percentage radioactivity eluting as 3H-1,25(OH)2D3 increased from approximately 2.4 +/- 1.9 to 16.2 +/- 8.0 after incubation with beta-glucuronidase. We conclude that significant amounts of intravenously administered 3H-1,25(OH)2D3 are excreted in bile, mostly as more polar metabolites. The increase in free 3H-1,25(OH)2D3 after incubation with beta-glucuronidase indicates that glucuronides of 1,25(OH)2D3 are present in bile.
Adult↗
Direct and indirect measurements of osteoid seam width in human iliac crest trabecular bone.
The osteoid thickness index, calculated from the relative osteoid volume and surface, has been compared with the mean osteoid seam width, measured directly, in iliac crest trabecular bone from 57 normal subjects and 33 patients with privational or malabsorption metabolic bone disease. In normal biopsies the osteoid thickness index overestimated mean osteoid seam width by a variable amount and the two variables were only weakly correlated (r = 0.32, P less than 0.01). In patients with hyperosteoidosis there was a stronger correlation between the osteoid thickness index and the true mean seam width (r = 0.89, P less than 0.001). Examination of the mean width of individual seams pooled from 15 randomly selected patients in each group revealed a skewed distribution with thin seams predominating, especially in normal biopsies. Median seam width was significantly lower than mean seam width in both groups studied. We conclude that osteoid thickness index is an inaccurate method of predicting the mean osteoid seam width, especially in biopsies with normal osteoid amount. Median values of osteoid seam width are more representative of average seam width, both in normal and abnormal biopsies.
Adult↗
Measurement of total resorption surface in iliac crest trabecular bone in man.
Total resorption surface has been measured under ordinary light and polarized light in trabecular iliac crest bone from 57 healthy subjects and 40 patients with privational or malabsorption metabolic bone disease. Results obtained with the two methods were similar, although values for total resorption surface measured under polarized light were usually lower than those obtained under ordinary light in both groups of subjects studied. This most likely reflects the greater accuracy in the microscopic identification of resorption surface under polarized light.
Adult↗