Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort.

OBJECTIVE: Bisphosphonates are considered potential disease modifying osteoarthritis (OA) agents. The present study investigated the efficacy of pre-emptive, early, and delayed alendronate (ALN) treatment initiation on subchondral trabecular bone and cartilage in low-dose monosodium iodoacetate (MIA)-induced knee OA in rats. METHODS: Male rats received pre-emptive (n = 12, day 0-end of week 2), early (n = 12, end of week 2-end of week 6), or delayed (n = 12, end of week 6-end of week 10) ALN treatment (30 µg/kg/week). Pre-emptive ALN-treated rats were scanned using in vivo micro-computed tomography (micro-CT) after 2 weeks and then sacrificed, early ALN-treated rats were scanned after 2 and 6 weeks and sacrificed, and the delayed ALN-treated rats were scanned after 2, 6, and 10 weeks of OA induction and sacrificed. After sacrifice, bone histomorphometry and histology of the tibia and biomarker analyses were undertaken. Changes in hind limb weight-bearing were assessed from day -1 until day 14. RESULTS: MIA-induced pathological features similar to progressive human OA in the cartilage and subchondral bone. Pre-emptive ALN treatment preserved subchondral trabecular bone microarchitecture, prevented bone loss, decreased bone turnover and joint discomfort. Pre-emptive ALN treatment had moderate effects on cartilage degradation. Early and delayed ALN treatments prevented loss of trabeculae and decreased bone turnover, but had no significant effect on cartilage degradation. CONCLUSION: ALN prevented increased bone turnover and preserved the structural integrity of subchondral bone in experimental OA. The time point of treatment initiation is crucial for treating OA. Treating both the subchondral bone and cartilage in OA would be clinically more beneficial.

Vertebral body bone strength: the contribution of individual trabecular element morphology.

SUMMARY: Although the amount of bone explains the largest amount of variability in bone strength, there is still a significant proportion unaccounted for. The morphology of individual bone trabeculae explains a further proportion of the variability in bone strength and bone elements that contribute to bone strength depending on the direction of loading. INTRODUCTION: Micro-CT imaging enables measurement of bone microarchitecture and subsequently mechanical strength of the same sample. It is possible using micro-CT data to perform morphometric analysis on individual rod and plate bone trabeculae using a volumetric spatial decomposition algorithm and hence determine their contribution to bone strength. METHODS: Twelve pairs of vertebral bodies (T12/L1 or L4/L5) were harvested from human cadavers, and bone cubes (10 × 10 × 10 mm) were obtained. After micro-CT imaging, a volumetric spatial decomposition algorithm was applied, and measures of individual trabecular elements were obtained. Bone strength was measured in compression, where one bone specimen from each vertebral segment was tested supero-inferiorly (SI) and the paired specimen was tested antero-posteriorly (AP). RESULTS: Bone volume fraction was the strongest individual determinant of SI strength (r(2) = 0.77, p < 0.0001) and AP (r(2) = 0.54, p < 0.0001). The determination of SI strength was improved to r(2) = 0.87 with the addition of mean rod length and relative plate bone volume fraction. The determination of AP strength was improved to r(2) = 0.85 with the addition of mean rod volume and relative rod bone volume fraction. CONCLUSIONS: Microarchitectural measures of individual trabeculae that contribute to bone strength have been identified. In addition to the contribution of BV/TV, trabecular rod morphology increased the determination of AP strength by 57%, whereas measures of trabecular plate and rod morphology increased determination of SI strength by 13%. Decomposing vertebral body bone architecture into its constituent morphological elements shows that trabecular element morphology has specific functional roles to assist in maintaining skeletal integrity.

Variation in segmentation of bone from micro-CT imaging: implications for quantitative morphometric analysis.

Segmentation of bone in grey-level tomographs from micro-CT imaging is critical in determining the accuracy of morphometric analysis. The degree of variability in image segmentation between and within multiple operators will be quantified and compared with automated image segmentation. Three cubes of cancellous bone were cut from T12, L1, L3 and L4 human vertebral bodies (n=12). Micro-CT imaging was performed and a global threshold was determined by 3 operators independently and automatically using Otsu's algorithm. Bone volume, trabecular thickness, trabecular separation, trabecular number, trabecular bone pattern factor, structure model index and degree of anisotropy were calculated. Percent bias and percent random error were calculated between all operators and Otsu's method. For BV/TV, the maximum percent bias and percent random error were 22.0% and 11.3%, respectively, which constitutes differences in individual measurements between operators of up to 0.07. For Tb.Th, the maximum percent bias and percent random error were 13.1% and 6.4%, respectively, which constitutes differences in individual measurements between operators of up to 35 microm. These data highlight to users of micro-CT imaging that morphometric analysis is highly sensitive to operating parameters. The effect on measurements of cancellous bone structure of different operators can be greater than experimental differences, which can lead to erroneous interpretation of results.

Microcomputed tomography imaging in a rat model of delayed union/non-union fracture.

We aimed to develop a clinically relevant delayed union/non-union fracture model to evaluate a cell therapy intervention repair strategy. Histology, three-dimensional (3D) microcomputed tomography (micro-CT) imaging and mechanical testing were utilized to develop an analytical protocol for qualitative and quantitative assessment of fracture repair. An open femoral diaphyseal osteotomy, combined with periosteal diathermy and endosteal excision, was held in compression by a four pin unilateral external fixator. Three delayed union/non-union fracture groups established at 6 weeks--(a) a control group, (b) a cell therapy group, and (c) a group receiving phosphate-buffered saline (PBS) injection alone--were examined subsequently at 8 and 14 weeks. The histological response was combined fibrous and cartilaginous non-unions in groups A and B with fibrous non-unions in group C. Mineralized callus volume/total volume percentage showed no statistically significant differences between groups. Endosteal calcified tissue volume/endosteal tissue volume, at the center of the fracture site, displayed statistically significant differences between 8 and 14 weeks for cell and PBS intervention groups but not for the control group. The percentage load to failure was significantly lower in the control and cell treatment groups than in the PBS alone group. High-resolution micro-CT imaging provides a powerful tool to augment characterization of repair in delayed union/non-union fractures together with outcomes such as histology and mechanical strength measurement. Accurate, nondestructive, 3D identification of mineralization progression in repairing fractures is enabled in the presence or absence of intervention strategies.

Mechanical and pathologic consequences of induced concentric anular tears in an ovine model.

STUDY DESIGN: Relations between induced concentric tears in the sheep disc and the mechanics of the intervertebral joint and vertebral body bone were analyzed. OBJECTIVE: To examine the effect of concentric disc tears on the mechanics of the spine. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc results in changes to the mechanics and morphology of the spine, but the effect of concentric disc tears is unknown. METHODS: In this study, 48 merino wethers were subjected to surgery, and discs were randomly selected for either a needlestick injury or induction of a concentric tear in the anterior and left anterolateral anulus. Sheep were randomly assigned to groups for killing at 0, 1, 3, 6, 12, and 18 months. From each sheep, two spine segments were mechanically tested: one with a needlestick injury and one with a concentric tear. Macroscopic disc morphology was assessed by three axial slices of the disc. Sagittal bone slices were taken from cranial and caudal vertebral bodies for histologic analysis. RESULTS: Induced concentric tears decrease the stiffness of intact spine segments in left bending and the disc alone in flexion. In all other mechanical tests, the needlestick injury had the same effect as the induced concentric tear. In the isolated disc, the disc stiffness at 6 months was increased for right bending, as compared with the response at 1 month. This was associated with increased anterior lamellar thickening and increased vertebral body bone volume fraction. CONCLUSIONS: Concentric tears and needlestick injury in the anterior anulus lead to mechanical changes in the disc and both anular lamellar thickness and vertebral body bone volume fraction. A needlestick injury through the anulus parallel to the lamellae produces progressive damage.

Intervertebral disc disorganization is related to trabecular bone architecture in the lumbar spine.

Cancellous bone morphometry was investigated in the sagittal plane of lumbar vertebrae using histoquantitation. The aim of this study was to identify variations in cancellous bone architecture at increasing states of intervertebral disc (IVD) disorganization after age adjustment and to investigate regional variations within the whole vertebral body. Measurements were taken of the ratio of bone volume (BV) to total volume (TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N). Lumbar spines (T12-L5) of 19 men and 8 women were removed at autopsy from an adult sample with no clinical history of bone-related disease or histologically identifiable bone disease. It was found that degeneration of the IVD becomes more common with increasing age. After age-adjustment, significant increases in the proportion of BV/TV were observed in the presence of advancing IVD disorganization. Significant architectural changes were observed in the anterior regions of the vertebral body with increases in Tb.Th and Tb.N and decreases in Tb.Sp. Minimal alterations were found at posterior regions. Bone loss was observed in central regions (most distant from the cortex) as IVD disorganization increased through reduction in both Tb.N and Tb.Th. The BV/TV increase in anterior areas of the centrum may be a response to a redistribution of load to the vertebral body periphery as a result of IVD disorganization. It appears that trabecular morphology is related to the condition of the associated IVD, rather than being the sole consequence of a loss of BV/TV with age. This relationship could influence the occurrence of vertebral body crush fracture.

Intervertebral disc disorganisation and its relationship to age adjusted vertebral body morphometry and vertebral bone architecture.

Vertebral deformity, intervertebral disc disorganisation, and change to vertebral bone architecture are morphological features that are associated with low back pain. The purpose of this study was to examine the influence of the morphological disorganisation of the intervertebral disc on vertebral body shape indices and vertebral cancellous bone architecture. Lumbar spines, T12-S1, were collected from 27 cadavers. The motion segments T12-L1, L2-L3 and L4-L5 were selected for the study. There were 8 females aged 35-94 years and 19 males aged 20-90 years. An intervertebral disc grade signifying the severity of disc disorganisation was assigned to each disc using the macroscopic disc grading criteria of Hansson and Roos (Spine, 1981; 6:147-153.). Vertebral shape indices and vertebral body bone histomorphometric analyses were performed on the vertebral bodies. Where appropriate, data were age adjusted and the influence of morphological disc disorganisation on vertebral body deformity and cancellous bone architecture analysed. Increased vertebral body axial area and the ratio of vertebral body axial area to sagittal area were associated with an increase in vertebral deformity and disc disorganisation. This suggests that vertebral deformity that remains clinically silent in the general population is influenced by intervertebral disc disorganisation. Vertebral cancellous bone architecture undergoes change associated with increased disc disorganisation, consistent with increased vertebral deformity. Vertebral bodies adjacent to degenerate discs (Grade 4) showed increased BV/TV and Tb.Th and decreased BS/BV. This shows that disc disorganisation may modulate vertebral cancellous bone architecture such that it protects against age-related bone changes. In addition, vertebral body wedging and concavity are associated with smaller vertebral body size and vertebral body compression is associated with larger vertebral body size and compromised cancellous bone architecture.

Methodological principles for fractal analysis of trabecular bone.

A standardized methodology for the fractal analysis of histological sections of trabecular bone has been established. A modified box counting method has been developed for use on a PC-based image analyser. The effect of image analyser settings, magnification, image orientation and threshold levels was determined. Also, the range of scale over which trabecular bone is effectively fractal was determined and a method formulated to calculate objectively more than one fractal dimension from the modified Richardson plot. The results show that magnification, image orientation and threshold settings have little effect on the estimate of fractal dimension. Trabecular bone has a lower limit below which it is not fractal (lambda < 25 microm) and the upper limit is 4250 microm. There are three distinct fractal dimensions for trabecular bone (sectional fractals), with magnitudes greater than 1.0 and less than 2.0. It has been shown that trabecular bone is effectively fractal over a defined range of scale. Also, within this range, there is more than one fractal dimension, describing spatial structural entities. Fractal analysis is a model-independent method for describing a complex multifaceted structure, which can be adapted for the study of other biological systems. This may be at the cell, tissue or organ level and complements conventional histomorphometric and stereological techniques.

Disc lesions and the mechanics of the intervertebral joint complex.

STUDY DESIGN: Correlations between tears in the disc and the mechanics of both the intervertebral joint and vertebral body bone were analyzed. OBJECTIVES: To examine the effect of disc degeneration on the mechanics of spinal motion segments. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc results in changes to the mechanics of the spine. The actual effect of tear type and size on the mechanics of the intervertebral joint is unknown. METHODS: Thirty spinal specimens (median age, 68 years) were divided into T12-L1, L2-L3, and L4-L5 motion segments. Mechanical tests recorded stiffness in flexion, extension, and torsion. Disc morphology was ascertained by taking three transverse sections of the disc and mapping and measuring the concentric tears, radial tears, and rim lesions. The severity of each tear type within each disc then was quantified. Bone cubes from the adjacent vertebral bodies were tested in compression to determine the elastic moduli and tested to failure in the longitudinal direction. RESULTS: Groups with tears were older and had reduced bone elastic moduli than groups without tears. Extension stiffness for the intact joint tended to increase with increasing tear severity. A decrease in torsional stiffness was present with increased severity of rim lesions at both L2-L3 and L4-L5. CONCLUSIONS: Tears in the intervertebral disc are reflected in a reduction in vertebral bone elastic modulus and in changes in the mechanics of the intervertebral joints in flexion, extension, and torsion.

Fractal properties of cancellous bone of the iliac crest in vertebral crush fracture.

Fractal analysis is a method for describing complex shapes, including the cancellous structure of bone. It describes the surface texture and form of individual trabecular profiles and the overall cancellous structure. Sixty-four postmenopausal women with symptoms of back pain were referred for investigation for osteoporosis. The patients were divided into two groups for comparison: vertebral crush fracture (n = 31, mean age 68.58 +/- 6.47 years), and no vertebral crush fracture (n = 33, mean age 63.36 +/- 7.21 years). Cores of cancellous bone, 3 mm in diameter, were taken from the iliac crest and sectioned. A box-counting method implemented on an image analyzer was used to measure the fractal dimension. Three fractal dimensions describing trabecular surface texture (fractal 1), trabecular shape (fractal 2), and trabecular arrangement (fractal 3) were measured, indicating that cancellous bone has sectional self-similarity. Conventional histomorphometry was also performed on the samples. The results show that fractal 2 is significantly lower in the vertebral crush fracture group than in the nonfracture group (1.15 +/- 0.10 < 1.23 +/- 0.090, p < 0.0013). The histomorphometric analysis shows that bone surface total volume (p < 0.0002), trabecular number (p < 0.0001), and osteoid surface bone surface (p < 0.028) are significantly lower in the fracture group than the nonfracture group. Eroded surface/bone surface (p < 0.056) follows this trend, whereas trabecular separation (p < 0.001) is significantly higher in the fracture group than in the nonfracture group. Fractal 1 and fractal 3 were not significantly different between study groups. The fractal dimension detects changes in the cancellous architecture and gives information about iliac bone transformation in postmenopausal women with vertebral fracture.

Sequence analysis of the mip gene of the soilborne pathogen Legionella longbeachae.

To understand the basis of pathogenesis by Legionella longbeachae serogroup 1, the importance of the Mip protein in this species was examined. Amino-terminal analysis of the purified, cloned L. longbeachae serogroup 1 ATCC 33462 Mip protein confirmed that the cloned gene protein was expressed and processed in an Escherichia coli background. DNA sequence analysis of plasmid pIMVS27, containing the entire L. longbeachae serogroup 1 mip gene, revealed a high degree of homology to the mip gene of Legionella pneumophila serogroup 1, 76% homology at the DNA level and 87% identity at the amino acid level. Primer extension analysis determined that the start site of transcription was the same for both species, with some differences observed for the -10 and -35 promoter regions. Primers designed from the mip gene sequence obtained for L. longbeachae serogroup 1 ATCC 33462 were used to amplify the mip genes from L. longbeachae serogroup 2 ATCC 33484 and an Australian clinical isolate of L. longbeachae serogroup 1 A5H5. The mip gene from A5H5 was 100% identical to the type strain sequence. The serogroup 2 strain of L. longbeachae differed by 2 base pairs in third-codon positions. Allelic exchange mutagenesis was used to generate an isogenic mip mutant in ATCC 33462 and strain A5H5. The ATCC mip mutant was unable to infect a strain of Acanthamoebae sp. both in liquid and in a potting mix coculture system, while the A5H5 mip mutant behaved in a manner siilar to that of L. pneumophila serogroup 1, i.e., it displayed a reduced capacity to infect and multiply within Acanthamoebae. To determine if this mutation resulted in reduced virulence in the guinea pig animal model, the A5H5 mip mutant and its parent strain were assessed for their abilities to establish an infection after aerosol exposure. Unlike the virulent parent strain, the mutant strain did not kill any animals under two different dose regimes. The data indicate that the Mip protein plays an important role in the intracellular life cycle of L. longbeachae serogroup 1 species and is required for full virulence.

Femoral trabecular bone of osteoarthritic and normal subjects in an age and sex matched group.

OBJECTIVE: To describe changes to the cancellous structure of femoral bone from patients with severe primary osteoarthritis by comparison with age and sex matched controls. METHOD: Specimens were taken from 18 male and 18 female pairs. One of each pair was a normal control, the other having severe primary osteoarthritis which required hip arthroplasty. Undecalcified cancellous bone blocks were embedded in resin, sectioned and impregnated with silver. Histoquantitation was performed using image analysis. Using a plate model for the trabecular structure of bone, an estimate was made of bone volume, bone surface, trabecular thickness, trabecular separation and trabecular number. RESULTS: In osteoarthritis, pooled male and female data show a significant decrease in trabecular number together with an increase in trabecular thickness and separation. The statistical variance in the histomorphometric variables for each of the study groups was calculated and expressed as the ratio of osteoarthritic to control. This ratio shows that the variance of the osteoarthritic groups is significantly increased for each variable in the pooled data. The same trend is evident in the male and female groups. CONCLUSIONS: This quantitative study of cancellous bone architecture in the femoral head, infero-medial to the fovea, has found increased trabecular thickness and decreased trabecular number in patients with primary osteoarthritis. Increased morphometric variance has shown that severe osteoarthritis, contrary to osteoporosis, is associated with heterogeneous bone structures. These findings provide some basis for understanding how osteoarthritis may contribute to the prevention of osteoporotic fracture.

Fractal properties of subchondral cancellous bone in severe osteoarthritis of the hip.

Primary osteoarthritis of the hip results in changes to the architecture of subchondral cancellous bone. These changes in architecture occur through the action of osteoclasts and osteoblasts in selectively removing and adding bone. The quantitative description of the bone architecture helps in understanding the etiology of primary osteoarthritis. Fractal analysis is a method for describing complex shapes, which is expressed numerically as the fractal dimension. A box counting method was used, where the perimeter of binary profiles of cancellous bone samples was measured for different box sizes. The fractal dimension was the absolute value of the slope of the straight line segments from the plot of the log number of boxes versus the log box size. Cancellous bone samples from two subchondral regions, superior and inferomedial, to the fovea were analyzed from primary severe osteoarthritic specimens taken following total hip replacement surgery (n = 19, aged 51-80 years) and autopsy controls (n = 25, aged 18-90 years). There were three straight line segments identified on the log-log plot, for each subject, indicating a fractal dimension over three different ranges of scale. The results show that in the superior region there is a highly significant difference between the groups (p < 0.0001) for fractal 1 and pivot point 2. The histomorphometry shows significant differences for bone volume/total volume, bone surface/total volume, trabecular separation, and osteoid surface/total volume between groups. In the inferomedial region fractal 1 and fractal 2 are significantly different. For the histomorphometry, trabecular thickness and eroded surface/total volume are significantly different between the groups. The pivot points, i.e., the box size at which the fractal dimension changes, were of similar magnitude to the trabecular thickness and trabecular separation. These data suggest that the fractal geometry analysis of cancellous bone identifies architectural features not easily recognized by conventional bone histomorphometry. The fractal dimension is a descriptor of bone structure which simplifies the description of a complex structure and enables changes in cancellous bone architecture, due to disease, to be identified.

Principles of ploidy analysis by static cytometry.

Aims-To examine the basic assumptions made during DNA ploidy analysis of histological sections with an aim to eliminate methodological errors that have lead to conflicting results with this technique.Methods-A rat liver imprint and histological sections together with sections and whole nuclei cytospins of human breast tumour biopsy specimens were stained with azure A Schiff's reagent and used to investigate the effects of computer imaging, histological section thickness, nuclear volume, and shape corrections.Results-The rat liver imprint demonstrated a linear relation between mean nuclear transmittance and nuclear area for each of the three (2C, 4C, 8C) hepatocyte clusters. This finding was used to produce similar, proportional integrated optical density (IOD) measurements from rat liver sections by selecting only nuclei that were sectioned through their centres, as assumed by the mathematics for volume correction. The limitations of computer imaging necessitated an edge (glare) correction for each nucleus so that nuclei of different sizes could be analysed. Shape correction was required to analyse nuclei of different morphologies. Normal human lymphocytes, squamous epithelium and fibroblasts were all measured with similar IODs. DNA ploidy values obtained from 7 mum human breast tumour sections (using lymphocytes as controls) correlated well with those obtained from the whole nuclei cytospins from the same tissue blocks.Conclusions-With an improved understanding of the theoretical and technical aspects of ploidy analysis of tissue sections, reproducible and consistent results are possible. These results can be integrated into routine histopathology investigations alongside immunohistochemistry and molecular diagnostic techniques.

Fractal dimension and architecture of trabecular bone.

The fractal dimension of trabecular bone was determined for biopsies from the proximal femur of 25 subjects undergoing hip arthroplasty. The average age was 67.7 years. A binary profile of the trabecular bone in the biopsy was obtained from a digitized image. A program written for the Quantimet 520 performed the fractal analysis. The fractal dimension was calculated for each specimen, using boxes whose sides ranged from 65 to 1000 microns in length. The mean fractal dimension for the 25 subjects was 1.195 +/- 0.064 and shows that in Euclidean terms the surface extent of trabecular bone is indeterminate. The Quantimet 520 was also used to perform bone histomorphometric measurements. These were bone volume/total volume (BV/TV) (per cent) = 11.05 +/- 4.38, bone surface/total volume (BS/TV) (mm2/mm3) = 1.90 +/- 0.51, trabecular thickness (Tb.Th) (mm) = 0.12 +/- 0.03, trabecular spacing (Tb.Sp) (mm) = 1.03 +/- 0.36, and trabecular number (Tb.N) (number/mm) = 0.95 +/- 0.25. Pearsons' correlation coefficients showed a statistically significant relationship between the fractal dimension and all the histomorphometric parameters, with BV/TV (r = 0.85, P < 0.0001), BS/TV (r = 0.74, P < 0.0001), Tb.Th (r = 0.50, P < 0.02), Tb.Sp (r = -0.81, P < 0.0001), and Tb.N (r = 0.76, P < 0.0001). This method for calculating fractal dimension shows that trabecular bone exhibits fractal properties over a defined box size, which is within the dimensions of a structural unit for trabecular bone. Therefore, the fractal dimension of trabecular bone provides a measure which does not rely on Euclidean descriptors in order to describe a complex geometry.

Cancellous bone structure analysis using image analysis.

The application of image analysis techniques for the analysis of histology are developing rapidly particularly where it is possible to prepare high contrast histology sections. Bone histology is one such instance, bone matrix can be stained with van Geisen. This preparation is particularly suitable for image segmentation using grey level threshold detection. This study has quantified the bias and random error that can be attributed to pixel sizing and the threshold detection level. Also, the influence of the working magnification and the intra and inter observer variability on the reproducibility and reliability of image analysis results. The study has analysed vertebral cancellous bone structure in vertebrae with low bone volume (5.53%) and high bone volume (20.85%) at a range of magnification (x4 to x640). Data were collected at various machine settings and at different times by the machine operators. Data were analysed using Student's paired t-test. Variation from the optimum threshold detection level significantly influences the magnitude of bone volume, bone mineral surface and trabecular thickness measurements. Bone mineral surface measurement increases as the working magnification increases, identifying the fractal nature of cancellous bone. Operator bias is less than 5% though random error can be as high as 13%. Image analysis can be very efficient and make quantitative tissue analyses more accessible to scientists interested in studies of comparative pathology. This study shows that reproducible and reliable data for the analysis of cancellous bone structure can be obtained by the application of a clearly defined operating protocol and adequate operator training.

Trabecular spacing in post-menopausal Australian women with and without vertebral fractures.

Histomorphometric measurements were made from iliac crest biopsies of 32 women with vertebral fractures and 37 women without fracture. All were post-menopausal Australian women who had presented with back pain to a hospital out-patient endocrinology clinic. Bone from the fracture cases was characterised by loss of individual trabecular elements, with the remaining trabeculae being spaced further apart than those in the non-fracture women (p less than 0.0001). This resulted in a significant decrease in trabecular bone volume (p less than 0.01). In addition osteoid surface was reduced (p less than 0.01). Dynamic parameters of bone turnover were not significantly different between the two groups. These data should be useful for the assessment of iliac bone histomorphometry in Australian post-menopausal women suspected of having osteoporosis.

Aluminium intoxication in renal disease.

Aluminium intoxication in renal failure occurred over weeks or months when dialysis fluid or parenteral solutions were heavily contaminated and over many years when the main source was oral administration of aluminium-containing phosphate binders. Encephalopathy was common during subacute intoxication but in slow aluminium poisoning the main brunt was borne by the bones. However, in both tempos of intoxication several organs or systems were involved. Encephalopathy was usually accompanied by bone disease, bone disease by parathyroid suppression and both by anaemia. The heart and the lymphocytes are probably damaged by aluminium overload. Among the many questions left unanswered 15 years after the incrimination of aluminium as the cause of this multi-system illness are: (1) does low level aluminium overload in renal failure cause gradual deterioration in cerebral function? And, if so, (2) does it resemble Alzheimer's disease or a slow-onset version of dialysis encephalopathy? The evidence we review suggests that the answer to (1) is 'yes' and to (2) 'probably the latter'.

Correlations between the mechanical properties, radiology and histomorphometry of human femoral bone.

Initial fixation of the femoral components of total hip replacements is related to the mechanical integrity of the bone within the proximal femur. This preliminary study examined the correlations between the mechanical properties, histomorphometry, and radiology of bone core specimens taken from the proximal femora of cadavers and of patients undergoing total hip replacement surgery. Measurements and subjective assessments of the femoral bone from radiographs were shown to have poor correlation with both compressive mechanical properties and bone volume measurements. However, the mechanical properties of the bone core specimens and the histomorphometric measurements correlated well with the bone density measured by single-photon absorptiometry, indicating that this type of imaging technique may be of value in determining bone quality prior to surgery. The prediction of the mechanical properties of the proximal femur by preoperative imaging may have direct bearing on the type of femoral component to be used in total hip replacement. Preoperative assessment of bone quality would allow the surgeon to predict the likely fixation obtainable with different designs.

Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy.

Female Sprague-Dawley rats (n = 72), 6 months old, underwent either sham operation, oophorectomy, adrenalectomy, or combined oophorectomy and adrenalectomy (O&A). They were all maintained on normal saline ad libitum and 20 g/day 1.1% calcium chow. Nine weeks after operation, the trabecular bone volume of the distal femoral shaft was significantly lower (P less than 0.001) in the adrenalectomized (11.1%), oophorectomized (7.0%), and O&A (8.3%) animals than in sham-operated animals (19.8%). Eighteen weeks after operation, the trabecular bone volume in O&A animals had fallen to a mean of 3.8% (sham 17.0%), and the length of the femur had increased to 38.8 mm after O&A (sham 36.8 mm, P less than 0.01). O&A animals treated with 0.35 mg/kg/week nandrolone decanoate from 9 weeks postoperatively onward, had twice the femoral trabecular bone volume of untreated animals at 18 weeks (P less than 0.05). By contrast, no significant differences were found in vertebral body trabecular bone between any groups, including groups receiving treatment with androgens. We have found that, by 9 weeks after operation, adrenalectomy alone causes significant loss of metaphyseal trabecular bone, similar to the progressive loss seen after oophorectomy.