Impact loading of articular cartilage.
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Biomedical subjects
Publications and source records attributed to R M Aspden.
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For many years articular cartilage has been the focus of research aimed at improving understanding of and treatment for osteoarthritis. Although much is known about the tissue, research has had little success in elucidating the pathogenesis of generalised osteoarthritis. A new hypothesis is required. Substantial changes in many tissues, including bone, muscle, ligaments, and joint capsule, as well as cartilage, are increasingly recognised in this disease, and not all these changes are localised to the affected joints. There is also a well established link with obesity. These observations, the common origins of the mesenchymal cells that maintain these tissues, and the possible role of neuroendocrine factors that can regulate bone mass, result in the hypothesis that systemic factors that include altered lipid metabolism could explain the diversity of physiological changes in generalised osteoarthritis. If proven, this hypothesis could have important implications for a new approach to pharmacological intervention in the early stages of the disease.
Osteoporosis is a common disease with a strong genetic component. We previously described a polymorphic Sp1 binding site in the COL1A1 gene that has been associated with osteoporosis in several populations. Here we explore the molecular mechanisms underlying this association. A meta-analysis showed significant associations between COL1A1 "s" alleles and bone mineral density (BMD), body mass index (BMI), and osteoporotic fractures. The association with fracture was stronger than expected on the basis of the observed differences in BMD and BMI, suggesting an additional effect on bone strength. Gel shift assays showed increased binding affinity of the "s" allele for Sp1 protein, and primary RNA transcripts derived from the "s" allele were approximately three times more abundant than "S" allele--derived transcripts in "Ss" heterozygotes. Collagen produced from osteoblasts cultured from "Ss" heterozygotes had an increased ratio of alpha 1(I) protein relative to alpha 2(I), and this was accompanied by an increased ratio of COL1A1 mRNA relative to COL1A2. Finally, the yield strength of bone derived from "Ss" individuals was reduced when compared with bone derived from "SS" subjects. We conclude that the COL1A1 Sp1 polymorphism is a functional genetic variant that predisposes to osteoporosis by complex mechanisms involving changes in bone mass and bone quality.
STUDY DESIGN: A theoretical analysis of estimate the stresses generated in the anulus fibrosus by a loose fragment. OBJECTIVES: To test the hypothesis that a fragment can generate stress concentrations in an intervertebral disc that could lead to the progression of a fissure, and to provide a theoretical foundation for the laboratory model of lumbar disc protrusion, which proposes that a fragment is formed first and that prolapse is the final event of a chronic process. SUMMARY OF BACKGROUND DATA: A laboratory model was developed by Brinckmann and Porter in 1994, which indicated that introducing a fragment into an otherwise intact disc resulted in rapid failure of the disc under physiologic loads and flexion. Identical in vitro surgery with no reintroduction of fragments did not result in failure. METHODS: A theoretical model was developed in which a spherical fragment was impressed against a plane surface, representing the inner surface of the anulus. The stiffness of the sphere and that of the surface were varied, and the stresses generated in the anulus were calculated as a function of applied load. RESULTS: The contact stress and the shear stress increased as the stiffness of the fragment approached and exceeded that of the matrix. Increases in stiffness to more than four times that of the matrix resulted in little further increase in stress. Peak shear stresses are developed in the bulk matrix beyond the point of contact between the fragment and the anulus. For relatively small forces on the fragment, these stresses were comparable with those found in diarthrodial joints. CONCLUSIONS: It is shown that a fragment in an intervertebral disc produces localized areas of increased stress. Fatigue over long periods at these stresses could result in fissuring and premature failure of the tissue.
The subchondral bone plate supports the articular cartilage in diarthrodial joints. It has a significant mechanical function in transmitting loads from the cartilage into the underlying cancellous bone and has been implicated in the destruction of cartilage in osteoarthritis (OA) and its sparing in osteoporosis (OP), but little is known of its composition, structure or material properties. This study investigated the microscopic appearance and mineral composition of the subchondral bone plate in femoral heads from patients with OA or OP to determine how these correspond to changes in composition and stiffness found in other studies. Freeze-fractured full-depth samples of the subchondral bone plate from the femoral heads of patients with osteoarthritis, osteoporosis or a matched control group were examined using back scattered and secondary emission scanning electron microscopy. Other samples were embedded and polished and examined using back-scattered electron microscopy and electron probe microanalysis. The appearances of the samples from the normal and osteoporotic patients were very similar, with the subchondral bone plate overlayed by a layer of calcified cartilage. Osteoporotic samples presented a more uniform fracture surface and the relative thicknesses of the layers appeared to be different. In contrast, the OA bone plate appeared to be porous and have a much more textured surface. There were occasional sites of microtrabecular bone formation between the trabeculae of the underlying cancellous bone, which were not seen in the other groups, and more numerous osteoclast resorption pits. The calcified cartilage layer was almost absent and the bone plate was apparently thickened. The appearance of the osteoarthritic subchondral bone plate was, therefore, considerably different from both the normal and the osteoporotic, strongly indicative of abnormal cellular activity.
Hip fracture due to osteoporosis (OP) and hip osteoarthritis (OA) are both important causes of locomotor morbidity in the elderly population. In osteoporosis, bone mass gradually decreases until the skeleton is too fragile to support the body and a fracture occurs, typically in the femur, wrist, or spine. In osteoarthritis, there is a proliferation of bone, leading to a stiffening of the tissue. Current clinical methods for assessment of bone changes in these disorders largely depend on assessing bone mineral density. However, this does not provide any information about bone structure which is considered to be an equally important factor in assessing bone quality. This paper presents a novel approach for computer analysis of trabecular (or cancellous) bone structure. The technique uses a Fourier transform to generate a "spectral fingerprint" of an image. Principal components analysis is then applied to identify key features from the Fourier transform and this information passed to a neural network for classification. Testing this on a series of 100 histological sections of trabecular bone from patients with OP and OA and a normal group correctly classified over 90% of the OP group with an overall accuracy of 77%-84%. Such high success rates on a small group suggest that this may provide a simple, but powerful, method for identifying alterations in bone structure.
Cement fixation of the acetabular component is increasingly recognized as a common site of loosening when hip replacements fail. Cement keyholes drilled into the acetabulum have been recommended to improve this fixation but little is known of the optimum positions or sizes of these holes. This study investigates the diameter, depth and number of keyholes to be drilled to maximize the failure torque in a model system. A Taguchi experimental design was used to identify the most significant factors and to predict the best configuration of keyholes within the constraints of the experimental test rig. One hole at each of the pubic, iliac and ischial sites, of 12 mm diameter and 6 mm depth, was found to be the optimum configuration. The failure torque was most strongly dependent on the hole diameter in the pubic region, decreased with increasing hole depth and was not sensitive to the number of holes.
Connective tissues have primarily a mechanical function within the body. How each tissue derives its mechanical properties from its composition and structure and how these properties are maintained by the cells are still poorly understood. Some principles that may provide a unifying basis for the material properties of these tissues as materials is described. Given this understanding current studies in Aberdeen are investigating the ways in which cells may regulate these properties in response to mechanical stimuli.
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The stiffness, density and composition were compared in bone from the calcar femorale and cortical bone from the mid-shaft of the femur from an elderly group of clinically normal patients. Variation of properties through the thickness of the bone and the stiffness, measured using ultrasound, in directions parallel and perpendicular to the bone axis were also investigated. The calcar was less stiff (30.5 GPa) than the cortical bone (33.0 GPa) (P=0.04). It was also slightly less dense (2.01 compared with 2.05 g cm-3, P<0.001)and had a lower mineral content (56.7% of wet mass) than the femoral cortex (58.0%, P<0.05). At both sites the bone stiffness, density and mineral content decreased from the outer layer towards the inside. The stiffness was greatest in an axial direction and least in a radial direction with the tangential stiffness slightly greater than the radial, indicating an orthotropic symmetry. These results show that bone from the calcar has similar material properties to cortical bone, and provide a baseline for further studies investigating possible changes in the calcar in osteoporosis which may increase our understanding of the mechanisms underlying fractures of the neck of the femur.
OBJECTIVE: To determine the site variation of material properties and cellular biosynthetic activity, and to compare these at each site, of articular cartilage from the bovine carpo-metacarpal joint in order to test its usefulness as a model system for investigating the metabolic effects of mechanical stimuli. DESIGN: The mechanical properties and composition of full-depth biopsies of articular cartilage were measured at defined sites in bovine carpometacarpal joints. Metabolic activity at the same sites was assessed by incubating further biopsies in medium containing 35S-sulfate and 3H-leucine then measuring the incorporated radioisotope and cell density. These results were compared with an estimate of the distribution of forces across the joint. RESULTS: Topographical variation of water content, stiffness, cell count or incorporated radioisotope was not significant whereas collagen and glycosaminoglycan varied in different ways. A moderate correlation was found between water and collagen contents, but the correlation between water and glycosaminoglycan contents was poor. Neither compressive stiffness nor creep compliance was predicted strongly by any of the composition measurements. A negative correlation was found between metabolic activity and cell density. CONCLUSIONS: Defining the variation of tissue properties across the bovine carpometacarpal joint and the lack of variation in biosynthetic activity will enable proper matching of experimental and control groups of biopsies in studies of the effects of mechanical stimuli on the composition and mechanical properties of articular cartilage. In addition, the lack of correlation between stiffness, water and glycosaminoglycan contents is further evidence that the mechanical properties of the tissue depend significantly on factors other than these broad measures of composition.
STUDY DESIGN: Adverse factors during pregnancy may permanently stunt the growth of the spinal canal. Subsequently, even in an optimal environment the canal cannot catch up in growth with the trunk and long bones because of its early maturation. The degree of retardation in canal size depends on the severity and timing of the adverse effect. The catch-up growth of the long bones mask the narrow canal, because the latter does not have growth potential, resulting in an adult of sufficient height and good proportions, but with a canal at risk for stenosis. OBJECTIVES: To investigate the influence of the antenatal environment on the growth of the lumber spinal canal. SUMMARY OF BACKGROUND DATA: To date, little is known about the effects of an adverse environment on the growth of the spinal canal, and no data have been reported on antenatal influencing factors. METHODS: Lumbar magnetic resonance imaging scans from 58 patients were examined. Dimensions of the central spinal canals were measured by computerized image analysis and compared with the subjects' obstetric data from their mothers' pregnancies. RESULTS: The L3 canal was found to be the most sensitive to the influence of the examined factors. Gestational age was the most significant factor; if short, it resulted in small adult canal. Small placental weight, greater maternal age, primiparity, low socioeconomic class, and low birth weight were also found to be significant in affecting the growth of the canal. CONCLUSIONS: An adverse antenatal environment does have a permanent, retarding effect on the growth of the lumbar spinal canal.
Articular cartilage biopsies were subjected to a single impact load and the metabolic response of the chondrocytes investigated using radiolabelled precursors for protein ([3H]leucine) and glycosaminoglycan ([35S]sulfate). The severity of the impact was controlled by using different masses and drop heights in a purpose built drop tower. Loss of matrix components was studied by prelabelling prior to loading, the possible repair response by pulse labelling at defined intervals after loading. There was an increase in the loss of both labels from the tissue with increasing severity of impact though the patterns of loss were different. Only 25%-40% of the sulfate was lost over a two week period and the loss increased with the severity of impact. This contrasted with 60% of the leucine being lost over the same period independently of loading. In addition to the loss of synthetic activity caused by cell death, there was a suppression of incorporation immediately following loading. This eventually recovered and increased above control values but the recovery time appeared to depend on the severity of the impact. These results provide preliminary evidence for a repair response.
STUDY DESIGN: Lumbar motion segments were tested in vitro to examine biomechanical changes after posterior fixation by a flexible device. OBJECTIVES: To assess changes in load distribution and conformation of vertebral structures after a flexible stabilization. This should provide the foundations for a scientific understanding of the immediate effects of this surgical procedure. METHODS: Hooks were placed over the proximal spinous process and the distal laminas of a motion segment and connected by a polyester braid. Tension applied to the braid then generated a compression of the posterior elements. The force between the articular facets, the displacement of the posterior anulus fibrosus of the intervertebral disc, and the change in the relative position of the adjacent vertebrae were measured as the applied tension was increased. RESULTS: Facet joint force, disc bulge, and vertebral angulation increased with applied tension until a position of "locking" was achieved, apparently when the bony margin of the superior half of the facet joint contacted the inferior pars interarticularis. A tension of between 50 to 100 N in the braid was required for this. Facet joint force was less than 40% of this, and disc bulge was only 0.15 mm. The extension of the motion segment was between 2 degrees and 8 degrees. CONCLUSIONS: The results suggest that if such a system is applied surgically, stabilization is produced by compaction of the bony margins of the facet joints. Only a relatively small proportion of the posteriorly applied load is carried by the facet joints themselves, and little angulatory change is expected with minimal disc bulge.
Patients with osteoarthritis (OA) rarely fracture the neck of the femur whereas this is common in patients with osteoporosis (OP). The reasons for this are not clear. In this study, cores of trabecular bone and thin slices of bone from the calcar were obtained from the femoral neck of patients with OA or OP following hip arthroplasty and a normal group post mortem. The mechanical properties, densities and material composition were measured. The aim was to determine whether differences in these properties could explain why osteoarthritic patients did not suffer from fractured neck of femur. No difference was found in the density or stiffness of the calcar between the groups, though there appeared to be a small increase in mineralization in the OA bone compared with the OP. However, there was a 72% increase in the volume of trabecular bone in the OA group compared with a loss of about 20% in the OP group. This increased apparent density of the OA trabecular bone resulted in a greater stiffness, yield strength and energy absorbed to yield, whereas the same properties of OP bone were not significantly lower than normal. These marked changes in the OA bone could result in a redistribution of stresses due to loads caused by falling, thereby absorbing the energy of impact and preventing the formation of a fracture surface.
OBJECTIVE: To determine the material properties of the subchondral bone plate in patients with osteoarthritis or osteoporosis. METHODS: Femoral heads were obtained after surgical removal from age and sex matched groups of patients with either osteoporosis (OP), after a fractured neck of femur, or osteoarthritis (OA) and compared with a normal group. The mechanical stiffness, density, and composition of the subchondral bone plate from sites selected to represent areas of heavy, intermittent, and light loading were measured. RESULTS: Overall, OP bone was the least stiff and dense, followed by OA bone; normal bone was stiffer and more dense (p < 0.05). Though OP bone contained less mineral, the organic and water contents were increased in proportion suggesting no change in the relative amount of organic matrix. OA bone was also hypomineralised (p < 0.05) but had different organic and water fractions suggesting a defect in the matrix. Site variation of most properties was small, though across all the groups the superior region was significantly stiffer than the inferior. CONCLUSION: This study shows that subchondral bone plate is less stiff than normal in both OP and OA and so cannot, by itself, explain the preserving of the overlying cartilage in OP while aiding its destruction in OA. However, the subchondral bone plate is only one part of the bony structure of the femoral head and changes in the cancellous bone need to be considered. The generalised changes in bone composition found in patients with OA support the hypothesis that the disease could involve the bone in the primary pathogenesis.
The material properties of cancellous bone from patients with osteoporosis (OP) or osteoarthritis (OA) were determined and compared with normal controls. Samples were selected from defined sites in human femoral heads which are subjected to different loads in vivo. Overall, OP bone had the lowest stiffness and OA the highest, and this same order was reflected in the apparent densities of the bone, with OA being the most dense and OP the least. Normal and OP bone were found to have very similar stiffness-density relationships and composition. However, OA bone differed significantly from normal. The stiffness of OA bone increased more slowly with apparent density and its material density was significantly reduced. These findings were due to an altered composition of the bone in which the mass fraction of mineral is 12% less than normal. There was also greater site variation of both apparent and material density, suggesting an altered sensitivity to applied load. These results support the concept that osteoporosis is a loss of normal bone. They also provide evidence for the hypothesis that osteoarthritis is, at least partly, a bone disease in which proliferation of defective bone results in an increase in bone stiffness.
The upright thoraco-lumbar spine resembles an Euler column buckled in the second mode (n = 2) when viewed in the sagittal plane. An advantage of n = 2 buckling is that further load can be carried without adopting a stooped posture. Flexion of the spine is considered as the first quarter cycle of an Euler pendulum. This is possible if the antagonistic muscles which control movement increase the bending stiffness, EI, to a value of about 15 N m2. If the muscles are incapable of increasing EI sufficiently to support the weight of the body, or any excess load, the spine will be dynamically unstable. This conclusion is consistent with a static model which considers spinal instability as 'loss of stiffness' and a dynamic model which suggests that it arises from ineffective adaptive control. The flexed spine resembles an n = 1 buckled column.