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.

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.

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 (

Purpose In the literature, inter-vertebral MRI signal intensity changes (Modic changes) were associated with corresponding histological observations on endplate biopsies. However, tissue-level studies were limited. No quantitative histomorphometric study on bone biopsies has yet been conducted for Modic changes. The aim of this study was to characterise the bone micro-architectural parameters and bone remodelling indices associated with Modic changes. Methods Forty patients suffering from disabling low back pain, undergoing elective spinal surgery, and exhibiting Modic changes on MRI (Modic 1, n = 9; Modic 2, n = 25; Modic 3, n = 6), had a transpedicular vertebral body biopsy taken of subchondral bone. Biopsies were first examined by micro-CT, for 3D morphometric analysis of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation, trabecular number, and structure model index. Then, samples underwent histological analysis, for determination of bone remodelling indices: osteoid surface to bone surface ratio (OS/BS), eroded surface to bone surface (ES/BS) and osteoid surface to eroded surface ratio (OS/ES). Results Micro-CT analysis revealed significantly higher BV/TV (up to 70 % increase, p \ 0.01) and Tb.Th (up to ?57 %, p \ 0.01) in Modic 3 biopsies, compared to Modic 1 and 2. Histological analysis showed significantly lower OS/BS in Modic 2 biopsies (more than 28 % decrease, p \ 0.05) compared to 1 and 3. ES/BS progressively decreased from Modic 1 to 2 to 3, whereas OS/ES progressively increased with significantly higher values in Modic 3 (up to 159 % increase, p \ 0.05) than in Modic 1 and 2. Conclusions Significant differences were found in bone micro-architectural parameters and remodelling indices among Modic types. Modic 1 biopsies had evidence of highest bone turnover, possibly due to an inflammatory process; Modic 2 biopsies were consistent with a reduced bone formation/remodelling stage; Modic 3 biopsies suggested a more stable sclerotic phase, with significantly increased BV/TV and Tb.Th compared to Modic 1 and 2, linked to increased bone formation and reduced resorption.

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.

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 μm 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,P0·0001), BS/TV (r=0·74,P0·0001), Tb.Th (r=0·50,P0·02), Tb.Sp (r=−0·81,P0·0001), and Tb.N (r=0·76,P0·0001). 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.

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. (J Bone Miner Res 1997;12:632-640)

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.