The quality of bone in the skeleton depends on the amount of bone, geometry, microarchitecture and material properties, and the molecular and cellular regulation of bone turnover and repair. This study aimed to identify material and structural factors that alter in fragility hip fracture patients treated with antiresorption therapies (FxAr) compared to fragility hip fracture patients not on treatment (Fx).

Bone from the intertrochanteric site, femoral head (FH: FxAr = 5, Fx = 8), compression screw cores and box chisel were obtained from patients undergoing hemi-arthroplasty surgery, FxAr (6f, 2m, mean 79 and range [64–89] years), and Fx (7f, 1m, age 85 [75–93] years). Control bone was obtained at autopsy (9f, 4m, 77 [65–88] years). Treated patients were on various bisphosphonates. Samples were resin-embedded, for quantitative backscattered electron imaging of the degree of mineralisation and assessment of bone architecture. Trabecular bone volume fraction (BV/TV) and architectural parameters were not significantly different between FxAr and Fx groups.

Both groups showed normal distributions of weight (wt) % Ca; however, the FxAr was less mineralised than the Fx and the control group (mean wt % Ca: FxAr = 24.3%, Fx = 24.8%, Control = 24.9%). When comparing the FH specimens only, we found that BV/TV in the FxAr was greater than the Fx group (18% vs 15%). All other parameters were not significantly different. In addition, the mineralisation was greater in the FxAr group compared to the Fx group (25.5 % vs 25.0%) but was not significantly different.

Collectively, these data suggest the effect on bone of antiresorptives may be different for patients on antiresorptive treatment that do not subsequently fracture. Assessment of bone material property data together with other bone quality measures may hold the key to better understanding of antiresorptive treatment efficacy.

Introduction: Disc degeneration causes structural and biochemical tissue changes resulting in altered stresses that may affect vertebral bone remodelling. We hypothesized that disc degeneration alters vertebral cortical strains and disc mechanics of the motion segment, with and without the presence of zygapophyseal joints.

Methods: Twenty human lumbar functional spinal units (FSUs) were strain gauged on the lateral and anterior vertebral cortices, below the inferior endplate. Each FSU was preloaded overnight (0.2 MPa) in a bath and subjected to dynamic compression (1 MPa), flexion/extension/lateral bending (500N + 5 Nm), and axial rotation (5 Nm), before and after removal of the zygapophyseal joints. After testing, discs were macroscopically assessed and graded (1–4) for degeneration. Stiffness, phase angle (energy absorption) and principal strains were calculated. ANOVAs with the dependent variable of principal strain/stiffness/phase angle versus disc grade were performed for each testing direction.

Results: Assessment of disc degenerative condition revealed six grade 2 discs, eight grade 3, and six grade 4. Age and degeneration were highly correlated (r=0.80, P< 0.0001). The effect of disc grade on stiffness was significant overall in most loading directions, before and after removal of zygapophyseal joints (P< 0.008), apart for axial rotation (P> 0.587). Post-hoc multiple comparisons for all loading directions apart for axial rotation revealed that the stiffness of grade 4 discs was significantly larger than grades 2 and 3 discs in most loading directions.

For phase angle (approximate magnitude 5°), no significant overall effects due to degeneration were found across any loading direction (P> 0.2). ANOVA analyses on maximum/minimum principal strains found no significant effect due to disc grade (P> 0.063). However, a small number of significant effects due to disc grade were found at particular strain gauge locations for the isolated disc in flexion, the intact FSU in extension, and the intact FSU/isolated disc in right lateral bending.

Discussion: This study represents the first of its kind to investigate the effects of disc degeneration on vertebral bone cortical strain and disc mechanical properties. Significant increases in stiffness were found with increasing degeneration in all test directions apart for axial rotation. Changes in disc stiffness were consistent with other studies and may be a result of the structural and biochemical changes within the disc that accompany the degenerative process.

The non-significant small phase angles suggest that the disc behaves more like an elastic solid than a poroelastic material, and that dehydration associated with degeneration does not adversely affect damping. Principal strains were not significantly affected by disc degeneration overall, suggesting that the cortical shell adjacent to the disc-endplate boundary maintains a relatively homeostatic condition, with more dramatic architectural changes probably occurring within the trabecular bone. Applications of this research include providing important validation data for analytical/finite element models of the intact FSU and isolated disc segment, and a better understanding of the magnitudes of cortical strains that need to be maintained in order to avoid damaging vertebral bone stress-shielding effects after treatments for disc degeneration.

The anulus fibrosus of the human lumbar intervertebral disc has a complex, hierarchical structure comprised of collagens, proteoglycans and elastic fibres. Recent histological studies have suggested that the elastic fibre network may play an important functional role. In this study, it was hypothesised that elastic fibres enhance the mechanical integrity of the extracellular matrix transverse to the direction of the collagen fibres.

Using a combination of biochemically verified enzymatic treatments and biomechanical tests, it was demonstrated that degradation of elastic fibres resulted in a significant reduction in both the initial modulus and the ultimate modulus, and a significant increase in the extensibility, of radially oriented anulus fibrosus specimens. Separate treatments and mechanical tests were used to account for any changes attributable to non-specific degradation of glycosaminoglycans. Additionally, histological assessments provided a unique perspective on structural changes in the elastic fibre network in radially oriented specimens subjected to tensile deformations.

The results of this study demonstrate that elastic fibres play an important and unique role in the mechanical properties of the anulus fibrosus, and provide the basis for the development of improved material models to describe intervertebral disc mechanical behaviour.

Evidence is accumulating for the role of bone in the pathogenesis of osteoarthritis (OA). Previous studies have shown a generalised increase in bone mass and hypo-mineralisation in OA patients. However, the molecular and cellular mechanisms involved in the increased bone mass and matrix compositional profiles in OA, at distal skeletal sites to the articular cartilage, have not yet been well defined. This study examined whether gene expression of bone anabolic factors, trabecular bone architecture and matrix mineralisation are altered in human OA and non-OA hipbone. Intertrochanteric (IT) trabecular bone samples were obtained from 15 primary hip OA patients (mean age 65 [48–85] years) and 13 closely age- and gender-matched autopsy controls (mean age 63 [44–83] years). Semi-quantitative RT-PCR analysis revealed elevated mRNA expression levels of alkaline phosphatase (p < 0.002), osteocalcin (p < 0.0001), osteopontin (p < 0.05), collagen type-I α chains COL1A1 (p < 0.0001) and COL1A2 (p < 0.002), in OA bone compared to control, suggesting possible increases in osteoblastic biosynthetic activity and/or bone turnover at the IT region in OA. Interestingly, the ratio of COL1A1:COL1A2 mRNA was almost 2-fold greater in OA bone compared to control (p < 0.001), suggesting the potential presence of collagen type-I homotrimer at the distal site that may associate with hypomineralisation in OA individuals. Using a quantitative backscatter electron imaging technique, mineralisation profiles of IT trabecular bone indicated decreased mineralisation in the OA group compared to the control group (24.2 weight percent calcium [wt%Ca] versus 25.3 wt%Ca). Bone histomorphometric analysis found OA IT bone had increased surface density of bone and decreased trabecular separation compared to control bone. Taken together with a reported increase in diffuse microdamage in OA IT bone (Fazzalari et al. Bone 31:697–702, 2002), possibly due to hypomineralisation, these results are consistent with the altered bone material properties found in OA individuals. The finding of differential gene expression, altered mineralisation and architectural changes in OA bone, at a skeletal site distal to the active site of joint degeneration, supports the concept of systemic involvement of bone in the pathogenesis of OA.

Introduction The influence of annular tears on the biomechanical inter-relationship between the disc and vertebral body has a potentially important role in the mechanism of subsequent biological changes in disc and bone. The disc is a complex structure, exhibiting visco-elastic behaviour that is highly dependent on its condition and fluid content. Studies have shown that the stiffness of the disc is altered by its water content in human, ovine and bovine discs. It has also been shown that disc stiffness or modulus can be preserved if the level of water in the disc is kept constant. The importance of maintaining a reproducible state of stress in the disc during sequential testing of the same specimen is crucial to ensuring consistency of results and minimising systematic experimental errors. The aims of this study were to assess the reliability of sequential testing of the same specimen, and to determine whether stiffness, strains and pressure distribution can be restored to pre-testing levels under a uniform hydration loading environment.

Methods Six ovine FSUs with isolated discs were used in this study. Eight, 1-mm strain gauge rosettes were then bonded to the inferior VB of each FSU at lateral and anterior positions and three heights. FSUs were equilibrated for four hours in a saline bath at room temperature in a materials testing machine. A real-time pressure sensor was placed under the VB. FSUs were tested in axial compression at 0.1 Hz to 1 MPa for 5 sinusoidal cycles. Once tested, the FSU was placed under 0.25 MPa preload for one hour in the water bath for re-equilibration and tested again. Pilot studies by this group have shown that one hour is sufficient to return the disc to its original equilibrium state in a bath after testing, with no associated change in stiffness. This sequence was repeated four times to produce a total of five tests on each FSU. Outcome measures were FSU stiffness, axial strain, peak pressure, average pressure and contact area. Data was statistically analysed using intra-class correlation coefficients (ICC), and repeated measures ANOVA or paired t-tests.

Results The ICC for the five repeated stiffness measures was 0.24 (i.e 24% of the variation in the results was due to between-specimen tests with 76% of the variation due to within-specimen tests). Repeated measures ANOVA found no significant effect on stiffness due to repeating the test five times (P = 0.445). The ICC for the eight axial strains ranged from 0.8 to 0.99. There were no significant differences within any of the eight axial strains over the five repeats (P > 0.287). ICCs, and P values (in brackets) from repeated measures ANOVA, were 0.91 (0.179) for peak pressure, 0.85 (0.44) for average pressure and 0.99 (0.077) for contact area.

Discussion The largest systematic variation was seen for stiffness and this may be due to the tissue changes over the 9 hours of testing. Axial strains showed good to excellent agreement over the five repeated tests as did all pressure parameters. We conclude that the method of allowing one hour for re-equilibration in ovine discs produces a reproducible state of stress in the disc and minimises experimental errors.

Introduction The influence of annular tears on the biomechanical inter-relationship between the disc and vertebral body (VB) has a potentially important role in the mechanism of subsequent biological changes in disc and bone. It is postulated that changes in the disc may result in increased or abnormal spinal segment motion, modified load distribution across the spinal joint and altered cancellous bone architecture. There have been no studies investigating the direct effect of disc injury on functional spinal unit (FSU) stiffness and the distribution of pressure immediately adjacent to the disc inferior endplate. The aim of this study was to determine whether minor and severe radial tear injuries to the disc alters FSU stiffness and VB surface pressure distribution.

Methods Six ovine FSUs were used in this study. The posterior elements were removed leaving the isolated disc in each FSU. The inferior VB was transversely cut immediately inferior to the endplate and the neutral axis of bending (NAB) identified and marked. FSUs were equilibrated in a saline bath at room temperature for four hours under a constant preload of approximately 0.25 MPa prior to testing. After equilibration, FSUs were transferred to a saline bath in a materials testing machine (Instron 8511, Instron, High Wycombe, UK) and a real-time pressure sensor (I-Scan 5076, Tekscan Inc., MA, USA) placed under the inferior VB.

While maintaining the preload, FSUs were loaded in axial compression at 0.1 Hz through the NAB to 1 MPa in a saline bath for 5 sinusoidal cycles. Once tested, a radial tear was introduced via scalpel injury into the left postero-lateral region of the annulus and tested after one hour of re-equilibration. A final, more severe injury, in the form of removal of a 5 mm x 2 mm window of annulus at the same location was performed and tested after re-equilibration.

Outcome measures were FSU stiffness, peak pressure, average pressure, contact area, and centroid of force location. Data was statistically analysed using repeated measures ANOVA or paired t-tests.

Results No significant differences in stiffness was found as a result of disc injury (P = 0.857), nor for peak and average pressure, contact area and centroid location (P > 0.179).

Discussion These results may not be surprising given that the disc has been shown to be remarkably resilient under axial compression, even with a severe annular or nuclear injury. Further insight will be revealed when other modes of loading are performed in both ovine and human discs for the main study planned to be undertaken in the near future.

Introduction Dynamically identifying the distribution of pressure between any two given surfaces such as articulating joints is of fundamental importance in understanding their interaction. The purpose of this laboratory study was to assess the potential of a dynamic pressure measurement system, Tekscan. ( I-Scan 5076, Tekscan Inc., MA, USA) via a study which observed the changes in the load profile through the vertebral body of harvested ovine lumbar functional spinal units (FSU’s) with a created defect in the intervertebral disc.

The system was used to determine pressure distributions in isolated vertebral bodies inferior to the disc, during axial compression of normal and injured discs of an ovine functional spinal unit.

Methods Four ovine lumbar segments L1-L3 were harvested The superior vertebral body (VB) remained complete, whilst the inferior VB was sectioned 2mm from the endplate and the surface smoothed using emery paper in order to achieve maximum contact area. The neutral axis of bending for each specimen was identified and marked. In accordance with the manufacturer guidelines, the sensor was conditioned and calibrated between 20-200N of load. Testing was carried out in a materials testing machine (Instron 8511, Instron, High Wycombe, UK), where 200N of axial load was applied through the FSU and a snapshot of the instantaneous pressure distribution was taken. A 12 x 2 mm gap defect was created in the right ventro-lateral (2 specimens) and the right lateral (2 specimens) aspect of the IVD. The specimens were returned to the Instron and 200N of load was applied axially through the NAB. A recorded image of the pressure footprint was taken.

Results Comparing the recorded colour-coded images together with their centroids of force of the pre- and post-injury pressure distributions of the vertebral bodies, it was clearly evident that there was a major shift of the load through the IVD. As predicted and as seen in the pressure footprint, the pressure shifted in the opposing direction of the injury in order to maintain a balanced system. A pressure reading validation was also carried out with the use of the Instron, where the experimental pressure of the sensor was within 3% of the NATA calibrated load cell.

Discussion The system was used to sample pressure in real time and display it as a 3D colour-coded map, allowing for visualisation of normal pressure distributions. The associated software has numerous aids and functions, allowing real-time visualisation of the dynamic forces and the balance of forces across two interacting surfaces, making the system an invaluable analytical tool.

The Tekscan system will be used to observe the effect of disc injury on the pressure distribution of the adjacent vertebral body. The relationship between the pressure distribution across the vertebral body and bone architecture will also be studied

This study illustrated that this system is a valid tool for qualitatively and quantitatively assessing dynamic pressure distributions.

Introduction Vertebral deformity, disc disorganisation, and change to vertebral bone architecture are morphological features that are associated with degeneration of the spine and with back pain. Observations from our earlier studies found that the BV/TV is always a maximum in the inferior third of the vertebral body (VB), and minimum in the central third. Animal model studies have reported that the strain in loaded vertebra is a minimum in the central third of the vertebra. There have been no studies investigating the direct affect of VB removal on functional spinal unit (FSU) stiffness, strain magnitude and the distribution of pressure immediately adjacent to the sectioned VB. There were a number of aims for this study. The first aim was to determine whether the strain varies between supero-inferior locations on the VB. The second aim was to determine if strain symmetry was present across the normal VB. The third aim was to determine whether transverse sectioning of the VB alters the stiffness, strains and pressure distributions of the functional spinal unit (FSU) and VB.

Methods Six ovine FSUs with isolated discs were used in this study. Eight, 1-mm strain gauge rosettes were then bonded to the inferior VB of each FSU at lateral and anterior positions and three heights. FSUs were equilibrated in a saline bath at room temperature in a materials testing machine. A real-time pressure sensor was placed under the VB. FSUs were tested in axial compression at 0.1 Hz to 1 MPa for 5 sinusoidal cycles. The inferior VB was then sectioned transversely at 1/3 of its height and placed under preload for one hour for re-equilibration and re-tested. This procedure was repeated at 2/3 of VB height and immediately adjacent to the endplate. Outcome measures were FSU stiffness, axial strain, peak pressure and average pressure. Data was statistically analysed using repeated measures ANOVA or paired t-tests.

Results The results of the first aim found no significant difference in strains within the right lateral or left lateral (P > 0.134) columns of strain gauges. However, for the anterior column of strain gauges, the superior strain was 30% higher than the inferior strain (P = 0.047). The results of the second aim found no significant differences between laterally opposing strain gauges (P > 0.139). For the third aim, transverse sectioning of the VB over three levels produced no significant differences for FSU stiffness (P = 0.275), strains for any strain gauge (P > 0.087), or peak and average pressures (P > 0.076).

Discussion This complex pilot study has shown that overall, axial cortical strain in a normal, ovine FSU did not vary with VB supero-inferior location laterally, but did vary anteriorly. Strains were symmetrical between laterally opposing VB locations at each of three levels, and was not affected by transverse sectioning of the VB at three levels. The finding that anterior column strains differ, may relate to changes in load distribution governed by VB surface second moment of area differences (laterally compared to anteroposteriorly), and the absence of a disc inferiorly. Further insight will be revealed when other modes of loading are performed in both ovine and human discs for the main study planned to be undertaken in the near future.

Introduction: The development of scoliosis in pinealectomised chickens was first observed by Machida¹ and since reported by others. That melatonin deficiency following pinealectomy may be a factor in causing scoliosis has been postulated. The relationship between pinealectomy, scoliosis and serum melatonin levels has been subject to experimental investigations. This study reports the incidence and type of scoliosis in pinealectomised, sham operated and unoperated chickens, and related serum melatonin levels.

Methods: Serum melatonin levels were obtained at sacrifice up to six weeks postoperatively. Radiological and histological examination of the spine was performed.

Results: The vertebral motion segment comprises a synovial joint lacking any discs. 19% of the un-operated group had a sharp angular deformity in contrast to the smooth curve seen in adolescent idiopathic scoliosis (AIS). There was a 38% incidence of scoliosis after sham operation (mostly of the angular variety) and a 75% incidence in the pinealectomy group (of which half were smooth curves similar to those in human AIS. Melatonin was not abolished by pinealectomy or sham operation but was at significantly lower levels than in the unoperated group. There was no difference in Melatonin levels between birds with the two types of curves.

Discussion: The avian spine has fundamental structural differences with the human. There is a natural incidence of short angular scoliosis that increases with posterior fossa surgery in the chicken. We confirm that scoliosis similar to AIS forms after pinealectomy but it is not directly related to diminished melatonin levels.

The cancellous bone adjacent to major load-bearing joints such as the hip and knee has complex architecture. The loading patterns across these joints influence the architecture of the cancellous bone, which varies according to the magnitude and direction of these forces. Articular lesions are associated with alterations in the loading patterns and hence change to the cancellous architecture. The fractal dimension, as a numerical descriptor of complex shapes, enables these changes to be quantitated.

The fractal analysis was performed by a box counting method. The perimeter of binary profiles of cancellous bone samples was measured for different box sizes. The fractal dimension is 1-D (where D is the slope of the straight-line segments from the plot of log of perimeter versus of log box size). Samples of cancellous bone were taken at autopsy from three subchondral regions, superior to the fovea in the femoral head (n=56) and the tibial (n=25) and femoral (n=25) condyles of the knee. 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. Fractal 1 describes the complexity of bone surface detail influenced by osteoclast and osteoblast activity, fractal 2 describes the shape or form of individual trabeculae and fractal 3 describes the overall spatial complexity of the cancellous structure.

The results show that for fractal 1, all three regions are the same. For fractal 2, the femoral head is greater than the condyles (1.40±0.07 versus 1.36±0.05 and 1.36±0.05) and for fractal 3, the femoral head is significantly greater than the condyles (1.76±0.06 versus 1.73±0.04 and 1.70±0.05).

These data show that cancellous bone architecture differs between skeletal sites. In particular, the fine surface detail influenced by bone cell activity and described by fractal 1 is the same in each region, while the shape of individual trabeculae as described by fractal 2 is more complex in the femoral head. The overall spatial complexity of the cancellous structure as described by fractal 3 is the same in each condyle of the knee while in the femoral head it is significantly greater. The fractal dimension, as a descriptor of complexity, enables the effect of differences in the mechanical micro-environment on cancellous bone architecture to be quantified so that pathology affecting these regions can be studied.

The presence of microdamage in bone and its targeted repair by activating bone remodelling has been controversial partly because it is difficult to locate and difficult to quantify. A number of studies have now validated techniques to locate and quantify microdamage and microdamage repair in human cortical and trabecular bone samples. The purpose of this study is to determine if microcracks accumulate in the cancellous bone of the intertrochanteric region of the proximal femoral shaft and influence the strength of bone. We have used en bloc basic fuchsin staining to identify in vivo microcracks in 70 micron sections. Trabecular bone was sampled in 33 patients undergoing total hip replacement for primary osteoarthritis. The study sample had a median age of 73 years and included 18 women (aged 49 to 84 years) and 15 men (aged 45 to 85 years). Histomorphometry was used to quantify the number of cracks in each case. In a selection of 12 cases the bone sample was also biomechanically tested to determine the cancellous bone strength. We found that microcracks accumulate with age, particularly after the age of about 60 years. This indicates that the bone from the elderly is more susceptible to fatigue damage than bone from the young. In addition, an increased number of microcracks in the cancellous bone significantly reduced the ultimate failure stress of the bone. Bone screws or pins placed in cortical or trabecular bone create microdamage adjacent to an implant, and the area in which this microdamage occurs is the same as that which subsequently remodels. Microdamage may be the result primarily of procedures during prosthetic implantation, but bone screws or pins can create stress concentrations that can be sites for initiation of new cracks. Therefore, if bone remodelling targets bone microdamage for repair then accumulation of microdamage around prosthetic implants may be responsible for the biologic responses which lead to implant loosening. This phenomenon is understudied in orthopaedic research and is an area requiring further investigation.

Purpose: The aim of this study was to examine the intervertebral disc (IVD) biomechanics in a sheep model with concentric tears.

Methods: Fifty two adult merino wethers were randomly allocated into two groups with circumferential tears introduced by injection with saline (group 1) or needle stick with no saline (group 2). They were then sacrificed at 0, 1, 3, 6, 12 and 18 months for biomechanical testing. An additional ten sheep were used as an unoperated control at time 0 (Group 0). Biomechanical tests on each functional spinal unit (FSU) and IVD were performed.

Results: The effect of procedure overall was significant for torsion (P< 0.022), axial compression (P< 0.014), extension (P< 0.001) and left lateral bending (P< 0.004) for both the FSU and IVD. In almost every case, both groups 1 and 2 were significantly stiffer than group 0 but no different to each other. The effect of time overall was significant for flexion (P< 0.0028) and right lateral bending (P< 0.022) for both the FSU and IVD. In torsion, twisting to the left was significant for the intact FSU (P=0.008) and twisting to the right for the isolated IVD (P=0.009).

Discussion: The results of this study show that any intervention in the disc alters the biomechanics compared to an unoperated control group. To our knowledge this has not been shown before and these findings may have relevance to any intervention into the disc in the patient.

The cellular and molecular mechanisms that lead to particular trabecular structures in healthy bone and in skeletal disease, such as osteoarthritis (OA), are poorly understood. Osteoclast differentiation factor (ODF) is a newly described regulator of osteoclast formation and function, whose activity appears to be a balance between interaction with its receptor, RANK, and with an antagonist binding protein, osteoprotegerin (OPG). We have examined the relationship between the expression of ODF, RANK and OPG mRNA, and parameters of bone structure and turnover, in human trabecular bone. Intertrochanteric trabecular bone was sampled from patients with primary hip OA (n=13; median age 66 years) and controls taken at autopsy (n=12; median age 68.5 years), processed for histomorphometric analysis and RNA isolated for RT-PCR analysis of ODF, RANK and OPG mRNA expression. The ratios of ODF/OPG and ODF/RANK mRNA are significantly lower in OA (1.78±0.98; 0.59±0.31) compared to the controls (3.41±1.94, p< 0.02; 2.53±1.5, p< 0.001). This suggests that in OA there is less ODF mRNA available per unit RANK mRNA, and that osteoclast formation may be reduced. Furthermore, eroded bone surface (ES/BS[%]) was significantly lower (p< 0.05) in the OA group (6.37±3.17) compared to controls (9.74±4.53). Stong associations were found between the ratio of ODF/OPG mRNA and bone volume (ODF/OPG vs BV/TV[%], r=−0.67; p0.05) and bone turnover (ODF/OPG vs ES/BS, r=0.93; p< 0.001; ODF/OPG vs osteoid surgace (OS/BS[%], r=0.80; p< 0.001) in controls. In contrast to controls, these relationships were not evident in the OA group, suggesting that bone turnover maybe regulated differently in this disease.

A clinical, radiological and histopathological study of femoral heads from 125 patients with fracture of the neck of the femur and from 30 cadavers was carried out to identify various risk factors. The findings showed that the Singh index was unreliable as a radiological indicator of the bone content of the femoral heads; that the bone content of the femoral head in patients sustaining a fracture of the femoral neck did not differ from that of the controls; that osteomalacia was not found in any of the heads examined; and that the distribution of trabecular microfractures did not support the hypothesis that fracture of the neck was the result of progressive fatigue. It was concluded that the single most important factor leading to fracture in this Australian population was injury caused by falls and that such injury was frequently associated with other disease processes.