Ian H. Parkinson

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.

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.

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 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.

Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis.

IntroductionOsteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate (MIA)-induced OA using in vivo micro-computed tomography (CT).MethodsMale Wistar rats received a single intra-articular injection of low-dose MIA (0.2 mg) in the right knee joint and sterile saline in the left knee joint. The animals were scanned in vivo by micro-CT at two, six, and ten weeks post-injection, analogous to early, intermediate, and advanced stages of OA, to assess architectural changes in the tibial subchondral bone. The articular cartilage changes in the tibiae were assessed macroscopically and histologically at ten weeks post-injection.ResultsInterestingly, tibiae of the MIA-injected knees showed significant bone loss at two weeks, followed by increased trabecular thickness and separation at six and ten weeks. The trabecular number was decreased at all time points compared to control tibiae. The tibial subchondral plate thickness of the MIA-injected knee was increased at two and six weeks and the plate porosity was increased at all time points compared to control. At ten weeks, histology revealed loss of proteoglycans, chondrocyte necrosis, chondrocyte clusters, cartilage fibrillation, and delamination in the MIA-injected tibiae, whereas the control tibiae showed no changes. Micro-CT images and histology showed the presence of subchondral bone sclerosis, cysts, and osteophytes.ConclusionsThese findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments.

Failure strength of human vertebrae: Prediction using bone mineral density measured by DXA and bone volume by micro-CT

Significant relationships exist between areal bone mineral density (BMD) derived from dual energy X-ray absorptiometry (DXA) and bone strength. However, the predictive validity of BMD for osteoporotic vertebral fractures remains suboptimal. The diagnostic sensitivity of DXA in the lumbar spine may be improved by assessing BMD from lateral-projection scans, as these might better approximate the objective of measuring the trabecular-rich bone in the vertebral body, compared to the commonly-used posterior-anterior (PA) projections. Nowadays, X-ray micro-computed tomography (μCT) allows non-destructive three-dimensional structural characterization of entire bone segments at high resolution. In this study, human lumbar cadaver spines were examined ex situ by DXA in lateral and PA projections, as well as by μCT, with the aims (1) to investigate the ability of bone quantity measurements obtained by DXA in the lateral projection and in the PA projection, to predict variations in bone quantity measurements obtained by μCT, and (2) to assess their respective capabilities to predict whole vertebral body strength, determined experimentally. Human cadaver spines were scanned by DXA in PA projections and lateral projections. Bone mineral content (BMC) and BMD for L2 and L3 vertebrae were determined. The L2 and L3 vertebrae were then dissected and entirely scanned by μCT. Total bone volume (BV(tot)=cortical+trabecular), trabecular bone volume (BV), and trabecular bone volume fraction (BV/TV) were calculated over the entire vertebrae. The vertebral bodies were then mechanically tested to failure in compression, to determine ultimate load. The variables BV(tot), BV, and BV/TV measured by μCT were better predicted by BMC and BMD measured by lateral-projection DXA, with higher R(2) values and smaller standard errors of the estimate (R(2)=0.65-0.90, SEE=11%-18%), compared to PA-projection DXA (R(2)=0.33-0.53, SEE=22%-34%). The best predictors of ultimate load were BV(tot) and BV assessed by μCT (R(2)=0.88 and R(2)=0.81, respectively), and BMC and BMD from lateral-projection DXA (R(2)=0.82 and R(2)=0.70, respectively). Conversely, BMC and BMD from PA-projection DXA were lower predictors of ultimate load (R(2)=0.49 and R(2)=0.37, respectively). This ex vivo study highlights greater capabilities of lateral-projection DXA to predict variations in vertebral body bone quantity as measured by μCT, and to predict vertebral strength as assessed experimentally, compared to PA-projection DXA. This provides basis for further exploring the clinical application of lateral-projection DXA analysis.

Interrelationships between structural parameters of cancellous bone reveal accelerated structural change at low bone volume.

This study shows that change to cancellous bone structure is bone volume‐dependent in a nonlinear manner. At low bone volume (<15%), trabecular thickness and trabecular separation change at a much greater rate than at higher bone volume. This suggests that the structural integrity of the cancellous bone may become rapidly compromised when bone volume falls below a critical value.

AGE-RELATED CHANGES IN FEMORAL TRABECULAR BONE IN ARTHROSIS

Age-related changes in the cancellous bone in selected regions of the proximal femur and iliac crest were assessed. An arthrosis group and a control cadaver group, partitioned into subjects younger and older than aged 50 years, were compared. The control group comprised 69 heads of femur and iliac crest samples. The arthrosis group comprised 28 consecutive heads of femur affected by primary arthrosis and an iliac crest biopsy taken during hip arthroplasty. Cancellous bone was sampled from four selected regions in the proximal femur. Histomorphometric estimates of percentage bone volume were determined using image analysis. In the young controls the bone volume was higher than that in the old controls for all the regions. In the arthrosis group the bone volume was higher than that of the old controls except for the subchondral principal tensile and medial to the greater trochanter regions. The old controls had regression of bone volume on age for the subchondral and medial principal compressive regions and the iliac crest. The arthrosis group had a minimal dependence of bone volume on age. Our study showed that primary arthrosis modulates the age dependence of bone volume in the proximal femur.

EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair

Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts. In the present study, we examined the role of EphB4 during bone repair after traumatic injury. We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter (Col1‐EphB4) and investigated the bone repair process up to 12 weeks postfracture. The data indicated that Col1‐EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild‐type mice. The fractured bones of Col1‐EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild‐type mice. These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture, as demonstrated by increased safranin O and von Kossa staining, respectively. Interestingly, Col1‐EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells (CFU‐F), with an increased capacity to form mineralized nodules in vitro under osteogenic conditions, when compared with those of the wild‐type control mice. Furthermore, Col1‐EphB4 mice had significantly lower numbers of TRAP‐positive multinucleated osteoclasts within the callus site. Taken together, these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones.

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.