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N Garrahan

Publications and source records attributed to N Garrahan.

9 recordsLinked to original sources
PubMed2003

The effects of hormone replacement therapy on cortical bone in postmenopausal women. A histomorphometric study.

Investigations of the actions of estrogen on the skeleton have mainly focused on cancellous bone and there are no reported histomorphometric studies of the effects of oestrogen on cortical bone in humans. The aim of this study was to investigate the effects of both conventional hormone replacement therapy (HRT) and high-dose oestradiol on cortical bone in postmenopausal women. Transiliac biopsies were obtained from nine postmenopausal women aged 54-71 yr before and after 2 yr (mean, 23.5 months) of conventional HRT and in seven postmenopausal women aged 52-67 yr after long-term, high-dose oestradiol implant therapy (at least 14 yr). Indices of bone turnover, remodeling, and cortical structure were assessed by image analysis. Cortical width was highest in the women treated with high-dose oestrogen therapy (2.29 +/- 0.78 mm; mean +/- SD) and lowest in untreated women (1.36 +/- 0.60 mm; P=0.014). The proportion of canals with an eroded surface was significantly lower in the high-dose oestrogen group than in women before or after conventional HRT (3.03 +/- 3.7% vs. 11.1 +/- 7.1% and 10.5 +/- 8.6%; P=0.017 and 0.05, respectively). Bone formation rate (microm2/microm/day) in untreated women was significantly higher than in the high-dose oestrogen group (0.121 +/- 0.072 vs. 0.066 +/- 0.045, respectively; P=0.05), values in women treated with conventional HRT being intermediate. Our results provide the first histomorphometric evidence in postmenopausal women of dose-dependent oestrogen-induced suppression of bone turnover in iliac crest cortical bone. There was also a trend toward higher wall width with increasing dose of oestrogen, consistent with the previously reported anabolic effect in cancellous bone.

Aged↗
PubMed1999

Regional differences in cortical porosity in the fractured femoral neck.

Although bone mass is a contributory risk factor for intracapsular hip fracture, its distribution and porosity within the femoral neck is also important for bone strength. In femoral neck biopsies from 13 women with intracapsular hip fracture (mean +/- SEM: 75.4+/-2.1 years, OP) and 19 cadaveric samples (9 men and 10 women [control], aged 79.4+/-1.7 years), a segmental analysis was used to quantify circumferential variations in the characteristics of cortical bone haversian systems. In female control femoral necks, there was an increasing porosity gradient between the inferior (I) (7.7+/-0.6%) and superior regions (S) (16.05+/-1.8%,p < 0.005). In walking, these regions undergo compression and tension, respectively. In men, a similar trend was observed, but the differences were not significant (I: 11.1+/-1.2%; S: 14.1+/-1.7%; p = 0.133). This porosity gradient was not maintained in the fracture group (I: 10+/-1%; S: 12.65+/-1.2%). In contrast, porosity in the fracture group was greatest in the anterior cortex, being 41% higher in that quadrant than in controls (p = 0.06). The areal density of haversian canals ranged from 16.7 to 21.3 canals/mm2 with no significant differences between fractures and controls. In the control women, mean canal diameter was highest in the superior region (60+/-2.8 microm), and these canals were significantly larger than those in the inferior region (49.4+/-1.4 microm, p < 0.05). This difference was less marked in the fracture cases (I: 53.21+/-2.5 microm; S: 59.1+/-2.8 microm; p = 0.0878). Although the mean canal diameter in the anterior quadrant of the fracture cases was higher than in the control women this did not reach significance (OP/F: 59.5+/-3 microm; control/F: 52.7+/-2.6 microm; p = 0.106). However, the proportion of "giant" canals with diameters >385 microm (defined as the top 0.5% in the controls) was doubled in the anterior region of the fracture cases (OP/F: 1.28%; control/F: 0.69%; p < 0.005). Porosity is related to the square of the canal radius; therefore, such canals make a substantial contribution to cortical porosity. Previous work has shown that the elastic modulus of bone decreases approximately as the square root of porosity. Therefore, the increased porosity and the higher prevalence of "giant" canals have a markedly negative influence on the ability of the cortical shell to withstand stresses associated with a fall. The mechanisms responsible for the localized generation of "giant" haversian canals, and ultimately the "trabecularization" of the cortex, require further investigation.

Adaptation, Physiological↗
PubMed1999

Structure of the femoral neck in hip fracture: cortical bone loss in the inferoanterior to superoposterior axis.

Although bone mass is a contributory risk factor for hip fracture, its distribution about the femoral neck is also important. Femoral neck biopsies were obtained from 13 females with intracapsular hip fracture (fracture: mean age 74.3 +/- 2.3 years [SEM]) and 19 cadaveric samples (control: 9 males and 10 females 79.4 +/- 1.7 years) and the areas of cortical and cancellous bone were quantitated in octants. In the control group, although males had larger bones than females, the proportions of cortical and cancellous bone were not different (p > 0.05) between the genders. The total amount of bone, as a proportion of bone + marrow, was significantly reduced in the fractures compared with the female controls (%Tt.Ar: fracture 27.83 +/- 1.18, female control 33.62 +/- 1.47; p = 0.0054). Reductions in cortical bone area occurred in all regions but particularly in the inferior, inferoanterior, and anterior octants (p < 0.05). There were no differences between cases and controls in the regional amount of cancellous bone (all regions, p > 0.178). Marked reductions in mean cortical bone width between the fracture and female control group occurred in the anterior, inferoanterior (31%), and superoposterior (25%) regions. Representing cortical widths as simple Fourier functions of the angle about the center of area (R2adj = 0.79) showed in the cases that there was preservation of the cortical bone in the inferior region, with the proportional loss of cortical bone being greatest in the inferoanterior and superoposterior regions. It is concluded that loss of cortical, rather than cancellous, bone predominates in cases of femoral neck fracture. This loss occurs primarily along the inferoanterior to superoposterior axis. As this axis bears the greatest strain during a fall, it is hypothesized that specific thinning of the cortex in these regions leads to an exaggerated propensity to fracture in those so affected, above that resulting from an equivalent general decrease in bone mass.

Aged↗
PubMed1997

Cortical remodeling following suppression of endogenous estrogen with analogs of gonadotrophin releasing hormone.

The effects of estrogen suppression on osteonal remodeling in young women was investigated using transiliac biopsies (eight paired biopsies + four single pre; three single post biopsies) taken before and after treatment for endometriosis (6 months) with analogs of gonadotrophin releasing hormone (GnRH). Estrogen withdrawal increased the proportion of Haversian canals with an eroded surface (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002), and alkaline phosphatase (ALP) 116%, p = 0.043) but not those showing tartrate-resistant acid phosphatase (TRAP) activity (p = 0.25) or a single label (p = 0.30). Estrogen withdrawal increased TRAP activity in individual osteoclasts in canals with diameters greater than 50 microns (p = 0.0089) and also the number of osteons with diameters over 250 microns (p = 0.049). ALP activity in individual osteoblasts was increased but not significantly following treatment (p = 0.051). Wall thickness was significantly correlated with osteon diameter (p < 0.001). In a separate group of patients (four pairs + one post biopsy) on concurrent treatment with tibolone, there was no significant increase in the osteon density, cortical porosity, median canal diameter, or the markers of bone formation and resorption. Enzyme activities and numbers of active canals were also not increased with the concurrent treatment, but there was still an increase in the osteon diameter. As previously shown for cancellous bone, estrogen withdrawal increased cortical bone turnover. We have now shown that resorption depth within Haversian systems was also increased with treatment. The enhanced TRAP activity in individual osteoclasts supports the concept that osteoclasts are more active following estrogen withdrawal in agreement with theoretical arguments advanced previously. Understanding the cellular and biochemical mechanisms responsible for increased depth of osteoclast resorption when estrogen is withdrawn may allow the development of new strategies for preventing postmenopausal bone loss.

Acid Phosphatase↗
PubMed1996

Cortical and cancellous bone in the human femoral neck: evaluation of an interactive image analysis system.

An interactive image analysis package was developed to examine whole cross-sections from the femoral neck. The package quantifies cortical width (Ct.Wi), cortical porosity (Ct.Po), and proportions of cortical, cancellous bone as a percentage of bone plus marrow area. Segmental analysis was used to quantify circumferential variations in bone distribution within the femoral cross-section. To evaluate reproducibility of data four independent operators analyzed previously prepared femoral neck sections from a 2000 BC population. Differences in total and circumferential distributions of cortical and cancellous bone with respect to gender and age of samples were demonstrated. Reproducibility was assessed using coefficients of variation (CV). Analysis of sections using a variable magnification, giving largest possible image size, rather than a set magnification reduced variation between operators for all measurements. Use of a calculated threshold significantly decreased variation between operators for the proportions of cortical and cancellous bone (p < or = 0.026). Dividing the image into 8 rather than 16 segments also improved reproducibility. There was little agreement between operators in the determination of cortical porosity. The mean CV for the other quantitative indices such as cortical width and proportions of cortical and cancellous bone ranged from 4.87% to 13.52%. The genders showed similar patterns in circumferential distribution of bone. Cortical width was significantly greater in the inferior region compared to the other areas, whereas percent cortical bone was lowest at the superior region. The center of mass (COM) for the younger age group was located anteriorly, whereas in the older samples the COM was located posteriorly of the center of area (p = 0.041). Basic data relating to cortical and cancellous bone of acceptable reproducibility in comparison with current standards in iliac histomorphometry can now be provided at modest cost in operator time and resources.

Adult↗
PubMed1993

Bone remodeling in hip fracture.

Hip fracture incidence has shown strong upward secular trends in many societies with wide differences in age adjusted incidence between nations. Falls and reduced physical activity have emerged as the strongest risk factors in epidemiological studies, while clinical investigations have pointed to secondary hyperparathyroidism as an important candidate cause of the loss of femoral cortical bone in old age. Until recently there have been few studies performed directly on the region of interest in the proximal femur. Non-invasive methodology using 85Sr has now been developed by our group for measuring bone formation and (with concurrent serial DXA densitometry) resorption in the femoral neck. Bone turnover averaged about 8% annually in controls. A group of younger cases of femoral fracture showed similar indices of total and regional bone formation to a control group; but their resorption was higher. To further investigate this, a femoral neck bone biopsy technique has been developed which can be applied to fracture cases treated by arthroplasty. Preliminary studies have established that the anatomical asymmetry of the neck in cross-section is considerable and imposes restraints on the interpretation of smaller or incomplete femur biopsies. Prospects are quite good that, in the absence of tetracycline pre-labeling, mineralization can be studied by assessment of alkaline phosphatase-positive surfaces in cryostat sections. Moreover, such sections will permit study of other anatomically localized metabolic activities as well as antigen expression and osteocyte viability. Candidate mechanisms for the regional decline in bone quality as well as bone mass in subjects suffering hip fracture can now be investigated more effectively.

Biomarkers↗
PubMed1992

Epithelial--stromal interactions in tumors. A morphologic study of fibroepithelial tumors of the breast.

BACKGROUND AND METHODS: The known spatial interaction between normal breast epithelium and its surrounding stroma prompted an investigation of the spatial relationship between stromal mitoses and the epithelial component of fibroepithelial tumors of the breast. The authors applied a novel computerized morphometric technique to routinely processed histologic sections of 23 fibroepithelial tumors (13 fibroadenomas and 10 phyllodes tumors). The proportional area of epithelium in successive concentric annuli surrounding stromal mitoses was measured, and its distribution was compared with that around suitable control points. RESULTS: The authors found that stromal mitotic activity in these tumors was significantly more likely to occur close to rather than remote from the epithelial component, with a significant excess of epithelium around mitoses compared with control points within a range of 79 microns. Essentially similar findings were obtained when randomly identified fibroblast nuclei were used as control points, thus obviating variations in stromal cell density with distance from epithelium as an explanation for the findings. CONCLUSIONS: These findings support the hypothesis that stromal growth in fibroepithelial tumors depends, to a variable extent, on the epithelial component. An interaction in the opposite direction (i.e., the stroma providing the growth support to the epithelium) also may occur, but this was not investigated. It is suggested that there is an interdependence of growth between the epithelial and stromal components in these tumors that explains their complex morphology and that stromal dependence on epithelium is lost with increasing malignancy of the stromal elements.

Adenofibroma↗
PubMed1982

Automated cell counting in tissue sections: a new approach by 'multiple grey-level analysis'.

A system is described for the automated quantitation in tissue sections of the follicular and stromal cell populations of the thyroid gland, using a computer-linked TV image analyser. The paper illustrates how the problems of variable staining intensity and clustering of images (nuclei) may be overcome by a novel approach, in which multiple analyses of each field are made at increasing grey-level thresholds, and then 'synthesized' by computer to give a composite image. Discrimination between cell (nuclear) types was by a single minimum width criterion. The results were highly reproducible and correlated well with counts obtained by a comparable manual method.

Animals↗