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Biomedical subjects

S Vedi

Publications and source records attributed to S Vedi.

35 records · Page 2Linked to original sources

Quantitative microfocal radiography of children with renal osteodystrophy; comparison with laboratory and histological findings.

High definition microfocal radiography permitted the quantitative assessment of the radiographic features of renal osteodystrophy in the phalanges of 11 children in stable chronic renal failure, treated with phosphate binders for 1 year. The most consistent feature was subperiosteal cortical resorption, expressed as a ratio total length of resorbed subperiosteal bone/total length subperiosteal bone x 100. It was found that the extent of resorbed bone was significantly greater in the middle phalanx and on the ulnar surface of the phalanges. The radiological findings over the duration of the disease were compared with laboratory assessments and bone histomorphometry. The extent of the percentage of subperiosteal resorption at base line and its change during the study period correlated significantly with the level of serum parathyroid hormone levels and its change over the same period. No other significant correlations were found between radiographic features and laboratory assessments or with bone histomorphometry.

Adolescent↗

The relationship between resorption depth and mean interstitial bone thickness: age-related changes in man.

The amounts of bone resorbed and formed in each bone remodelling unit are important determinants of bone mass. The mean wall thickness (MWT), which indicates the amount formed, decreases with age; less is known about changes in resorption depth although two studies have reported some evidence in favor of an age-related decrease. We have calculated mean intersitial bone thickness (MIBT), which is indirectly related to resorption depth, from measurements of MWT and mean trabecular plate thickness (MTPT) in 48 normal subjects, aged 19-80 years. No significant age-related changes in MIBT were found in either sex, or in both sexes grouped together, whereas MWT and MTPT showed a significant decrease with age (P less than 0.001 and less than 0.05 respectively). Detailed analysis of possible relationships between MIBT and resorption depth revealed that, assuming formation never exceeds resorption, a decreased MIBT may be associated with an increased, constant, or decreased resorption depth; an increased MIBT can only result from a decreased resorption depth. A constant MIBT may indicate either an unchanged or decreased resorption depth; in the former case, MTPT is unchanged whereas a decreased resorption depth is associated with a decreased MTPT. In view of the age-related reduction in MTPT, our results are therefore consistent with earlier reports of an age-related decrease in resorption depth. No evidence for an increased resorption depth during the menopause was found in this study.

Adult↗

Reduced bone formation in non-steroid treated patients with rheumatoid arthritis.

The cellular basis of trabecular bone loss in rheumatoid arthritis was investigated in 45 non-steroid treated patients. Mean wall thickness, an indicator of the amount of bone formed per remodelling unit, mean interstitial bone thickness, which is related to resorption depth, and the extent of trabecular surface covered by osteoid, which reflects the number of remodelling units, were assessed in iliac crest biopsy specimens. The mean wall thickness was significantly reduced in the patient group when compared with controls matched for age and sex (mean (SD) 39.8 (5.4) v 51.6 (9.7) microns). There was no significant difference between patients and controls in the mean interstitial bone thickness (51.0 (26.4) v 61.4 (31.9) microns) or osteoid surface (16.7 (11.4) v 21.0 (10.5)%). These results show that reduced bone formation at the remodelling unit level is the predominant mechanism of bone loss in rheumatoid arthritis.

Adult↗

Increased 3H-uridine levels in osteocytes following a single short period of dynamic bone loading in vivo.

Both ulnas of skeletally mature roosters (Gallus domesticus) were deprived of functional load bearing by proximal and distal submetaphyseal osteotomies. Twenty-four hours later the animals were injected with 1.5 mCi of 3H-uridine and the ulna on one side was subjected to a single period of a cyclical load engendering physiological strain levels at 1 Hz for 6 min. Twenty-four hours after loading the animals were killed. Autoradiographic examination of comparable regions of cortex in sections from the bone's midshafts showed that in the loaded bones, 72 +/- 2.7% of osteocytes were labeled compared with 12 +/- 3.5% in the corresponding areas of their contralateral nonloaded pair (P less than 0.001). The number of grains per labeled osteocyte was also higher in the loaded side (6 +/- 0.5 compared with 4 +/- 0.5, P less than 0.01). There was no obvious correlation between the longitudinal strain distribution during artificial loading and the distribution of labeled osteocytes throughout the bone cross-section. However, previous long-term experiments using a similar loading preparation had consistently shown the site of most periosteal new bone formation to also not be directly related to the local strain magnitude. Perhaps it is significant that the greatest percentage of labeled cells were found in the cortex where the long-term experiments had shown most new bone formation to subsequently occur.

Animals↗

Bone turnover and 1,25-dihydroxycholecalciferol during treatment with phosphate binders.

The effect of dietary phosphate restriction with high-dose aluminum hydroxide or calcium carbonate on bone disease assessed by histomorphometry and on the plasma levels of 1,25-dihydroxycholecalciferol was investigated in 12 children with chronic renal failure (GFR 8 to 45 ml/min/1.73 m2, age 5 to 15 years) over a one year period. Prior to treatment patients had biochemical and histological hyperparathyroidism with greatly increased bone formation rates. During treatment, plasma phosphate levels decreased from the upper to the lower limit of normal for age (pre, 1.69 +/- 0.06 mmol/liter; 6 months, 1.28 +/- 0.06 mmol/liter; 1 year, 1.34 +/- 0.06 mmol/liter; P less than 0.01). Circulating 1,25-dihydroxycholecalciferol rose to supranormal levels within three months and remained high throughout the period of study (pre, 96 +/- 32 pmol/liter; 6 months, 144 +/- 46 pmol/liter; 1 year, 169 +/- 53 pmol/liter; P less than 0.001). Significant falls in bone formation rate at tissue and cellular levels (P less than 0.005) and in total resorption surface (P less than 0.005) were observed. A mild mineralization defect present before treatment worsened, with a decrease in mineral appositional rate (P less than 0.01) and increase in mineralization lag time (P less than 0.01). Staining for aluminum in post-treatment biopsies was positive in 9 of 11 cases. Phosphate restriction produced suppression of biochemical and histological hyperparathyroidism and sustained elevation of circulating 1,25-dihydroxycholecalciferol. The adverse changes in bone mineralization may be related to aluminum hydroxide therapy; calcium carbonate is therefore recommended.

Adolescent↗

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↗

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↗

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↗

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↗

Bone histomorphometry and vitamin D status after biliopancreatic bypass for obesity.

Bone histomorphometry and vitamin D status were investigated in 41 patients studied 1-5 yr after partial or total biliopancreatic bypass. Metabolic bone disease, characterized by defective mineralization, decreased bone formation rate, and increased surface extent of resorption, was present in 30 patients (73%). Nine patients (22%) were hypocalcemic, but serum 25-hydroxyvitamin D concentrations were normal in all 41 patients. We conclude that metabolic bone disease is common after biliopancreatic bypass and usually occurs in the absence of simple vitamin D deficiency. The pathogenesis of the bone disease is unclear.

Adolescent↗

Value of the history in diagnosis of histological osteomalacia among Asians presenting to the NHS.

A questionnaire screening for osteomalacia was used to obtain histories from 53 consecutive Asian patients referred to a gastroenterology unit. 15 of the patients were found to have osteomalacia on subsequent histology. The questions that best distinguished between osteomalacic and non-osteomalacic patients were identified by discriminant analysis. These questions were used to derive discriminant functions by which a second sample of 45 Asian patients presenting to other parts of the National Health Service were classified as osteomalacic or non-osteomalacic. Bone histology showed false-negative and false-positive rates of 10% and 11%; the predictive value of the negative result was 97%. A short questionnaire would be a cheaper and more convenient method than biochemical screening for osteomalacia case-finding among Asian patients presenting to the NHS.

Alkaline Phosphatase↗

Histomorphometric analysis of bone biopsies from the iliac crest of normal British subjects.

Bone histomorphometric parameters have been measured in a group of normal British subjects of both sexes over a wide age range. There is loss of trabecular mineralized bone volume with advancing age and an increase in osteoid volume and in the trabecular bone surface covered by osteoid seams. There was no change in the mineral appositional rate or in bone resorption surfaces.

Adolescent↗

Value of plasma calcium, phosphate, and alkaline phosphatase measurements in the diagnosis of histological osteomalacia.

Plasma calcium and phosphate concentrations and alkaline phosphatase activities were examined retrospectively in 50 patients with histologically proven osteomalacia and 50 age- and sex-matched control subjects with normal bone histology. An abnormal plasma alkaline phosphatase activity was more useful than an abnormal plasma calcium or phosphate concentration in distinguishing between normal and osteomalacic subjects, producing a false-negative rate of 14% and a false-positive rate of 8%. False-negative and false-positive rates of 10% and 8% respectively were obtained when the presence of an abnormality in any one of the three biochemical measurements was used as a predictor of histological osteomalacia. When discriminant analysis was applied to plasma calcium, phosphate and alkaline phosphatase together a false-negative rate of 12% and a false-positive rate of 0% was obtained.Sixty-two patients in whom a diagnosis of osteomalacia was suspected were investigated prospectively, using both single biochemical abnormalities and the classification functions derived from the discriminant analysis of all three biochemical measurements to predict the presence or absence of histological osteomalacia. Plasma alkaline phosphatase activity gave false-negative and false-positive rates of 10% and 32% respectively but was a more reliable predictor of abnormal bone histology than were plasma calcium or plasma phosphate concentrations or the presence of an abnormality in any one of the three measurements. Discriminant analysis using plasma calcium, phosphate and alkaline phosphatase together produced a false-negative rate of 16% and a false-positive rate of 10%. We conclude that plasma alkaline phosphatase activity is the best single routine biochemical screening test for osteomalacia, although a high false-positive rate may occur. Direct discriminant analysis of plasma calcium, phosphate and alkaline phosphatase together provides a more sensitive method of detecting histological osteomalacia which should be useful in determining the prevalence of osteomalacia within high-risk populations.

Adolescent↗

Privational and malabsorption metabolic bone disease: plasma vitamin D metabolite concentrations and their relationship to quantitative bone histology.

Plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 25-hydroxyvitamin D (25OHD) concentrations were measured in twenty patients with metabolic bone disease due either to privational causes (10 patients) or malabsorption (10 patients). Abnormally low plasma 1,25(OH)2D3 levels were found in eleven patients, six with privational and five with malabsorption bone disease. Normal plasma 1,25(OH)2D3 concentrations were found in the remaining nine patients; of these, five were either receiving anticonvulsant therapy or had been hospitalised prior to investigation. In the absence of either of these factors, normal plasma 1,25(OH)2D3 levels were only found in patients with malabsorption-associated bone disease. Plasma 25OHD levels were below normal in eleven patients; six had malabsorption and five had privational bone disease. In the fifteen patients not receiving anticonvulsants there were significant inverse correlations between plasma 1,25(OH)2D3 levels and the osteoid volume, surface and seam thickness index. This study indicates that plasma 1,25(OH)2D3 concentrations are low in privational osteomalacia in the absence of anticonvulsant therapy or hospitalisation, although normal levels may occur in malabsorption metabolic bone disease uncomplicated by these factors. The plasma 1,25(OH)2D3 concentration appears to be inversely related to the histological severity of bone disease in patients not receiving anticonvulsant therapy.

Adult↗

Vitamin D status and bone histomorphometry in gross obesity.

Plasma 25-hydroxyvitamin D concentrations and bone histomorphometry were investigated in 24 grossly obese subjects. The mean plasma 25OHD concentration was significantly lower in the obese group than in age-matched, healthy controls. Subnormal values were found in four obese subjects and in a further two subjects, who were investigated at the end of the summer, plasma 25-hydroxyvitamin D levels were at the lower end of the normal winter range. Bone histology was abnormal in two patients. In one, mild osteomalacia and secondary hyperparathyroidism were present while in the other patient the appearance suggested increased bone turnover, possibly as a result of healing osteomalacia. We conclude that gross obesity is associated with an increased risk of vitamin D deficiency, probably because of reduced exposure to uv radiation. Histological evidence of metabolic bone disease may also occur. Preoperative vitamin D deficiency may contribute in some patients to the development of metabolic bone disease after intestinal bypass.

Adult↗

Histomorphometric analysis of dynamic parameters of trabecular bone formation in the iliac crest of normal British subjects.

Some dynamic parameters of bone formation in trabecular iliac crest bone have been measured in a group of normal British subjects of both sexes over a wide age range. There was a significant age-related decrease in mean wall thickness. When either double plus single or double only tetracycline-labeled surfaces were used to represent actively mineralizing surfaces, there was a significant age-related decrease in the bone formation rate at the basic multicellular unit level. Osteoid maturation period showed a significant age-related increase when calculated using double plus single labeled surfaces. There was no significant change with age in fractional labeled surfaces, mean osteoid seam width, bone formation rate at tissue level, or bone formation period. The mean osteoid seam width and osteoid maturation period were significantly higher in males than in females.

Adult↗