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Biomedical subjects

S Vedi

Publications and source records attributed to S Vedi.

11 recordsLinked to original sources

Combined inter-observer and inter-method variation in bone histomorphometry.

Manual methods for the measurement of bone biopsies have largely been superseded by semi-automatic computerised techniques.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.

Analysis of Variance

Low prevalence of osteomalacia in elderly patients with hip fracture.

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.

Aged

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

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