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.

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.

Three-dimensional confocal images of microdamage in cancellous bone.

The accumulation of microdamage in bone may contribute to loss of bone quality in osteoporosis, and the role of microdamage in the etiology of fatigue fractures is unknown. Microdamage created during testing, ex vivo, can increase the fragility of bone by decreasing the load necessary to cause fracture. Microdamage can also accumulate in vivo, but its influence on bone fragility is unknown. To date, stained microcracks are the only criteria to have been correlated with bone mechanics, leaving the influence of ultrastructural damage on bone fragility open for scrutiny. Staining en bloc has identified three morphological features in the tissue, discrete microcracks, cross-hatch staining, and diffuse staining. The relationship between these features and their identification as microdamage remains equivocal. The purpose of this study was to investigate the three-dimensional nature of microdamage in cancellous bone and also to describe stained microcracks, cross-hatch staining, and diffuse staining and to determine whether they all relate to microdamage in bone. Laser scanning confocal microscopy that provides improved spatial resolution over bright-field microscopy was used to visualize bone damage. It was found that crack surface density was highly correlated with crack density (r = 0.95, p < 0.0001), suggesting that the crack surface of preexisting cracks increases as new cracks are formed or submicroscopic cracks become visible under bright-field microscopy. Cross-hatch staining and diffuse staining included ultra-microcracks about 10 microm in length. The ultra-microcracks in cross-hatch staining were organized in bands and surrounded by diffuse staining. This study demonstrates that damage in bone occurs over a wide range and that discrete microcracks, cross-hatch staining, and diffuse staining are all indicative of bone damage. The diffuse staining still evident in association with the ultra-microcracks seen in cross-hatch staining and diffuse staining is probably due to damage at a still smaller scale than we have been able to investigate.

Assessment of cancellous bone quality in severe osteoarthrosis: bone mineral density, mechanics, and microdamage.

The role of bone microdamage (microscopic cracks or microcracks and ultrastructural collagen matrix and bone mineral damage) in diseases such as osteoarthrosis and osteoporosis is poorly understood. Microdamage accumulation in vivo is influenced by age and cyclic loading, therefore, it would be useful if the burden of microdamage in bone could be assessed by noninvasive measures such as the radiological measurement of bone mineral density (BMD). The aim of this study was to investigate the relationship between BMD, compressive strength and stiffness, and microdamage in the cancellous bone of the proximal femur in patients with severe osteoarthrosis. Trabecular bone core samples, from the intertrochanteric region of the femur, were obtained from 34 patients, with a mean age of 70.3 +/- 11.1 years, undergoing total hip arthroplasty for osteoarthrosis. Cores selected from contact X-ray images were used for BMD measurement, compressive mechanical testing or left untested (uncrushed), en bloc staining for microdamage, and bone histomorphometry. The study shows a strong dependence of both the elastic modulus and ultimate failure stress of the bone samples on BMD and a significant relationship between the elastic modulus and trabecular anisotropy (Tr. An). In multiple linear regression, BMD and Tr. An together account for about 70% of the variance in the elastic modulus. Then including microcrack crack density (Cr.Dn) and damage volume fraction (DxV/BV) variables, Tr. An alone accounts for a relatively small amount of the variation (8.5%) in ultimate failure stress and elastic modulus. The Cr.Dn accounts for more of the variation in the ultimate failure stress than in the elastic modulus (50% vs. 7%). In this experiment, data for Cr.Dn provide a measure of damage associated with the ultimate failure of cancellous bone. In specimens that were not mechanically tested, in vivo microcrack accumulation increases exponentially with age. In conclusion, data from this study suggest that BMD and Cr.Dn are the major determinants of cancellous bone strength, whereas BMD and Tr. An are major determinants of cancellous bone stiffness. In bone specimens subjected to compressive testing there was no relationship between microdamage and BMD, suggesting that BMD cannot be used to monitor changes in the mechanical properties of bone due to microdamage accumulation.

Pathogenesis of tears of the anulus investigated by multiple-level transaxial analysis of the T12-L1 disc.

STUDY DESIGN: Three transaxial slices, dividing each disc into four layers of equal thickness, were made in each of 19 T12-L1 discs. Naked-eye and stereoscopic examination was used to record abnormalities of the T12 (superior) surface of the upper slice, opposing surfaces of the central slice, and the L1 (inferior) surface of the lower slice. OBJECTIVES: To characterize and quantify structural abnormalities to determine their incidence and three-dimensional arrangement, and to test the hypotheses 1) that the frequency and location of tears of the anulus are related to age and nucleus condition; and 2) that rim lesions initiate the development of concentric tears. SUMMARY OF BACKGROUND DATA: Most previous studies of disc disease have been based on the examination of single sagittal slices, some on single transaxial slices, and a few have used both. This single-slice approach underrecords abnormalities that have not involved the disc center, and may inhibit the interpretation of magnetic resonance imaging and computed tomography images. METHODS: Spines from 19 human cadavers (mean age, 47.4 years; range, 20-79 years) were used. An initial transaxial slice through the center of the T12-L1 disc was followed by cranial and caudal transaxial slices midway between the center and endplate. Soft tissues were then removed to allow examination of the endplate. Abnormalities recorded at each stage were summated for all disc levels. The incidence of the abnormalities in each disc sector was analyzed using the Spearman-Rank correlation coefficient and the Bonferroni correction. RESULTS: With the exception of radiating tears, which most commonly affected the posterior disc, the right anterior quadrant tended to show abnormalities more frequently than the other quadrants. Although concentric tears (in 74%), rim lesions (in 47%), and radiating tears (in 47%) were frequent, no correlations were found between these three types of anulus tear. Concentric tears were present after approximately 10% of the anulus had undergone some delamination. Rim lesions correlated with focal thickening of anulus lamellae. One fifth of radiating tears extended to involve the outer anulus zone. CONCLUSIONS: Neither hypothesis was substantiated. Because lesions of the nucleus and anulus lack uniform shape and are three-dimensionally complex, it is inappropriate to interpret cadaver disc disease on single, mid-disc slices. The three different types of anulus tears appear to evolve independent of age and each other.

The relationship between head-neck-shaft angle, calcar width, articular cartilage thickness and bone volume in arthrosis of the hip.

The thickness of articular cartilage and the macroscopic and morphometric characteristics of bone in the proximal femur were assessed in a group of 28 surgically-treated patients with advanced idiopathic osteoarthrosis, and compared with the findings in a group of 16 non-arthrotic femora obtained at autopsy. In arthrosis, the BMI was increased, cartilage thickness at two principal stress sites was found to be significantly reduced, and the femoral head-neck-shaft angle was reduced. The calcar width of the cortical bone in the femur was unchanged. Bone volume was increased at the principal compressive region and diminished at both of the tensile regions. Regression analysis showed that in arthrosis calcar width was dependent on BMI and bone volume in the medial principal compressive region of the proximal femur. Furthermore, the volume of bone medial to the greater trochanter was significantly correlated with BMI.

The synovial response to intraarticular injection in rats of polyethylene wear particles.

To study the effect on tissues of wear particles commonly released from the articulating surfaces of joint prostheses, ultra-high-molecular-weight polyethylene particles were prepared in a joint simulator and injected into rat knees. The particles caused synovial proliferation and induced a macrophage and multinucleate giant-cell response in the subsynovium. Of particular interest was the macrophage response to particles ranging from 5 microns in maximum dimension to the limits of resolution of the light microscope; the multinucleate giant-cell response occurred in response to larger particles and aggregates of small particles. These findings emphasize the importance of wear particles in causing an adverse tissue response around joint replacements having a polyethylene component. The difference in cellular response to wear particles of different size suggests that not only the prosthesis material but also the pattern of wear and size of wear particles produced at the articulating surfaces of a prosthesis will determine the type of cellular response.

Comparative study of iliac crest and subchondral femoral bone in osteoarthritic patients.

This is a study of trabecular bone changes in selected regions of the femoral head. Iliac crest bone from osteoarthritic (OA) and control groups is compared to the bone from regions in the femoral head. The regions are the subchondral principal compressive and tensile areas. These areas of highest and lowest stress undergo dramatic change with OA. The compressive region has total cartilage loss and eburnation. Bone histomorphometry was done on undecalcified tissue sections stained by the von Kossa silver method and counter-stained with haematoxylin and eosin. Iliac crest histomorphometry is similar for the OA and control groups. The femoral trabecular structure in the stress regions changes in opposing directions with OA. In the compressive region the structural variables (BV/TV and BS/TV) increase [corrected], and in the tensile region decrease. Femoral bone turnover indices (OV/TV, OS/BS, and ES/BS) are no different, but femoral bone structure is different from that of the iliac crest. In OA patients there is no significant increase in iliac crest trabecular bone volume. The iliac crest is not useful to assess the bony changes in femoral OA.

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.

Comparative study of iliac crest and proximal femur histomorphometry in normal patients.

The relation between the bone histomorphometric profile of the iliac crest and regions of the proximal femur was investigated. In the proximal femur four blocks were selected, representing the subchondral principal compressive (SPC) and tensile (SPT) regions, the zone near the medial cortex in the principal compressive region (MPC), and the zone medial to the greater trochanter (MGT). Undecalcified tissue sections stained by the von Kossa silver method and counterstained with haematoxylin and eosin were used for quantitation. The SPT region was most representative of the iliac bone profile, in particular the structural parameters of mineralised bone, trabecular thickness, and trabecular spacing and resorption surface. Most parameters in the regions studied showed inconsistent and variable results when compared with those of the iliac crest. There was only a weak association, therefore, between the histomorphometric parameters of the iliac crest and the proximal femur despite the appeal of the use of the iliac biopsy specimen as a simple clinical test.

A rat model of resorption of bone at the cement-bone interface in the presence of polyethylene wear particles.

Resorption of bone and the formation of a membrane at the interface between acrylic cement and bone were induced by particles of high-density polyethylene that were similar in size to those that are present in the tissues surrounding a human joint prosthesis. A non-weight-bearing plug of methylmethacrylate was inserted through the knee joint into the distal part of the femur of the rat. The plug rapidly became surrounded by a shell of bone. After repeated injections of particles of high-density polyethylene into the knee joint, resorption of bone occurred at this stable interface. No resorption of bone occurred after the opposite knee was injected with a control preparation that did not contain particles. The resorption of bone that occurred around the plug after the injection of particles of polyethylene took place in the absence of mechanical causes for loosening and in the absence of infection.

Influence of prednisolone and methotrexate on cellular and biochemical aspects of acute and chronic inflammation studied in subcutaneously implanted sponges in rats.

The effects of prednisolone and methotrexate on the histology and the content of collagen and proteoglycans of the inflammatory tissue in polyurethane sponges impregnated with heat killed M. tuberculosis and implanted subcutaneously in hooded Wistar rats for up to 63 days were studied. Drugs were administered during the 6-day period before sponge removal 7, 21, 35, 49 and 63 days after implantation. Our findings indicate that prednisolone and methotrexate have profound effects on the cellular events of acute and chronic inflammation, and influence the synthesis or degradation of connective tissue macromolecules at certain stages of the inflammatory process.

The effect of isoxicam-aspirin combinations on the polyurethane sponge implantation model in the rat.

1 Anti-inflammatory effects of isoxicam alone and in combination with aspirin were studied in rats using the polyurethane sponge implantation model of acute inflammation. 2 Dose-response studies were performed to delineate a suppressive (high) and non-suppressive (low) dose of isoxicam prior to studying these doses in combination with aspirin. 3 The results indicate that a combination of aspirin with isoxicam does not have an additive anti-inflammatory effect. 4 The interference demonstrated by aspirin with the anti-inflammatory effects of other NSAIDs such as indomethacin is also demonstrated with aspirin/isoxicam combinations.

Distribution and elimination of coated polymethyl [2-14C]methacrylate nanoparticles after intravenous injection in rats.

Surfactant-coated polymethyl [2-14C]methacrylate nanoparticles had significantly different time-course distribution patterns in rats than noncoated and albumin-coated particles. Blood concentrations of poloxamer 188-coated particles were 70-fold higher after 30 min, and the particles persisted at higher levels in the circulation for up to 2 h. The initial and final liver levels were significantly lower (38% after 30 min, 51% after 7 d) and spleen levels were significantly higher (21% after 30 min, 23% after 7 d) than non-coated particles (74% in the liver and 5% in the spleen after 7 d) and the albumin-coated particles (84% in the liver and 5% in the spleen after 7 d). Specific activity was somewhat higher for the surfactant-coated particles in other organs such as the lungs, kidneys, testicles, ovaries, and lymph nodes. The bovine serum albumin sorption behavior of polymethyl methacrylate nanoparticles was followed under various conditions, and adsorption was found to increase with increasing protein concentration and increasing temperature, reaching a maximum at the isoelectric point of pH 4.9 after approximately 12 h of incubation. The zeta potential of the particles decreased with increasing pH, and the change was more pronounced with the albumin-coated particles.

Assessment of nonsteroidal anti-inflammatory drug combinations by the polyurethane sponge implantation model in the rat.

The anti-inflammatory effect of single doses and combinations of aspirin and commonly used nonsteroidal anti-inflammatory drugs was investigated by the polyurethane sponge implantation model of acute inflammation. Dose response curves were performed to delineate a suppressive (high) and nonsuppressive (low) dose of each drug prior to studying these doses in combination with aspirin. The results suggest that a combination of aspirin in either high or low dose does not increase the anti-inflammatory effect of other nonsteroidal anti-inflammatory drugs in this model of inflammation.