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Biomedical subjects

N J Garrahan

Publications and source records attributed to N J Garrahan.

14 recordsLinked to original sources

Characteristics of trabecular bone resorption cavities in patients with chronic renal failure.

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.

Adult

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Manual methods for the measurement of bone biopsies have largely been superseded by semi-automatic computerised techniques.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

Age-related changes in resorption cavity characteristics in human trabecular bone.

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.

Adult

The relationship between spinal trabecular bone mineral content and iliac crest trabecular bone volume.

The relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume has been studied in 84 patients, 23 with primary osteoporosis, 19 with osteoporosis secondary to inflammatory bowel disease, and 42 with nonsteroid-treated rheumatoid arthritis. Spinal trabecular bone mineral density was measured in the first three lumbar vertebrae by quantitative computed tomography, and iliac crest trabecular bone volume was assessed histomorphometrically in sections from trans-iliac biopsies using computerized techniques. In all 84 patients, there was a significant positive correlation between the two measurements (r = 0.60, P less than 0.001). However, when the three patient groups were analyzed separately, a significant correlation was found in the group with secondary osteoporosis (r = 0.65, P less than 0.01) but not in the patients with primary osteoporosis (r = 0.07) or rheumatoid arthritis (r = 0.19). These results indicate that the relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume differs according to the underlying disease process, these differences possibly reflecting variations in skeletal patterns of bone loss in different types of osteoporosis.

Adolescent

A computerised technique for the quantitative assessment of resorption cavities in trabecular bone.

A computerised technique is described for the quantitative assessment of resorption cavities in iliac trabecular bone. Using an Ibas II image analyser, the original bone surface, eroded by bone resorbing cells, is reconstructed using a curve fitting technique that maintains a smooth continuity with the trabecular bone on either side of the cavity. Resorption depths are measured using an interactive elastic circle; all identified cavities are measured regardless of whether or not resorption is complete, and the measurements made include mean and maximum cavity depth, cavity length, area, and adjacent trabecular widths. Results in 13 normal subjects are presented. The technique is reproducible, simple to operate, relatively rapid, and can be applied to less sophisticated image analysis systems.

Adult

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

Age-related changes in trabecular width and spacing in human iliac crest biopsies.

Age-related changes in trabecular width and spacing have been examined in iliac crest bone obtained from 96 normal subjects. The mean trabecular plate density and separation were calculated from values of trabecular bone volume and mean trabecular plate thickness. There was an age-related decrease in mean trabecular plate thickness with age in both sexes; this was statistically significant in males (P less than 0.02) but not in females. In females, there was a significant decrease in mean trabecular plate density (P less than 0.001) and increase in mean trabecular plate separation (P less than 0.001); similar but non-significant trends were observed in the males. These results demonstrate that trabecular thinning contributes to age-related bone loss in both sexes. Loss of trabeculae also occurs in both sexes, but to a greater extent in females than in males.

Adult

Structural mechanisms of trabecular bone loss in man.

The relationship between trabecular thinning and loss of connectedness of the trabecular bone pattern has been studied in iliac crest bone samples from 89 normal subjects in order to determine the structural mechanisms underlying age-related bone loss. Trabecular width and structure were quantitatively assessed using computerized techniques. Highly significant negative correlations were found between the mean trabecular plate thickness and number of free ends/mm2 both in males (r = -0.571) and in females (r = -0.667) (P less than 0.001). Mean trabecular plate thickness also showed significant negative correlations with other structural indices indicating reduced connectedness, whereas positive correlations were found with those indices representing preservation of connectedness. Examination of the relative frequency of trabecular widths less than 100 microns revealed that only 2-5% of the trabecular surface would be susceptible to erosion by a resorption cavity of normal depth. These results indicate that trabecular thinning and erosion are interdependent processes in age-related bone loss. Since only a small percentage of the trabecular surface is susceptible to erosion, and resorption cavities normally occupy only 1-5% of the total trabecular surface, these findings imply that the site of activation of new BMUs may not be randomly distributed but may instead be preferentially located at sites of lower trabecular width.

Adult

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

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