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Subchondral bone architecture and quality in osteoarthritis
Arthritis Res Ther volume 6, Article number: 39 (2004)
Osteoarthritis (OA) is traditionally seen as a disease of articular cartilage. However, changes in the bone that have long formed part of the radiological diagnosis – subchondral sclerosis, cysts and osteophytosis – are increasingly recognised as being an integral part of the disease. It is curious that cysts, regions of bone loss, are found in sites that are loaded, whereas osteophytes grow at the joint margins in sites that might be expected to be relatively lightly loaded. This is contrary to normal expectations of mechanical regulation of bone formation and resorption. Evidence from animal models of idiopathic OA suggests that bone changes may precede cartilage deterioration, which would indicate that they are part of the primary disease process. Patients with OA changes evident on hip radiographs were found to have a higher than average bone mineral density not only in the hip, but also in the distal radius, vertebrae and calcaneus.
These gross changes in the bone are reflected in the composition, structure and organisation of the trabecular bone and in the subchondral bone plate. There is massive proliferation of cancellous bone, by up to 60% by volume, throughout the femoral head and neck. Corresponding to this, histomorphometry has shown an increase in trabecular thickness, with a concomitant reduction in trabecular number, and an increase in osteoid width and eroded surfaces. A reduction in mineralisation is found in subchondral trabecular bone, perhaps reflecting a more rapidly formed woven bone-like tissue seen using scanning electron microscopy. This is reflected in a lower material density. Scanning electron microscopy also showed instances of abnormal bone formation in the trabecular spaces and a much greater number of Howship's lacunae indicating enhanced osteoclastic activity. A thickening of the subchondral bone plate has been reported in humans and cynomolgus macaques with OA, which also suggests an imbalance between bone formation and resorption. Changes are not limited to the affected joint. The iliac crest in women with hand OA has been found to have more bone, but with a mineralization profile shifting to higher densities, suggesting reduced bone turnover.
The proliferation of subchondral bone results in an increase in apparent, or tissue, modulus. Although the apparent modulus increases, the reduction in mineral content results in a reduction in the modulus of the bone matrix itself. Indentation studies showed a reduced hardness, and by implication modulus, in the subchondral bone matrix. Using thermal analysis and X-ray diffraction, we found no differences in crystallite size, unit cell dimensions or decomposition properties indicating, however, that the nature of the mineral itself, a carbonated apatite, was not altered.
Studies have implicated the receptor activator of NF-κB/receptor activator of NF-κB ligand/osteoprotegerin regulatory pathway by showing increased levels of mRNA for receptor activator of NF-κB and a decrease in the ratio of receptor activator of NF-κB ligand to osteoprotegerin. This ratio then failed to correlate with bone remodelling indices, unlike in the normal controls, suggesting a disruption of the regulation of bone remodelling. In addition, it has been suggested that the co-regulation of the mechanical properties of bone and cartilage does not function as normal. We have also shown that the femoral head contains twice the amount of fat per unit volume of cancellous bone tissue (including bone marrow) as osteoporotic bone and has elevated levels of (n-6) fatty acids, especially arachidonic acid.
Considerable changes in bone composition, architecture, quality and regulation are hallmarks of OA. It is still not clear whether these changes follow, precede or accompany the widely studied changes in articular cartilage. Subchondral bone does not appear to play a biomechanical role in the initiation of the disease. The widespread changes in bone, the frequent presence of multiple joint involvement and the link with obesity has lead to the suggestion of a systemic musculoskeletal disorder, in contrast to the traditional cartilage-first hypothesis.
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Aspden, R. Subchondral bone architecture and quality in osteoarthritis. Arthritis Res Ther 6, 39 (2004). https://doi.org/10.1186/ar1374
- Subchondral Bone
- Average Bone Mineral Density
- Cynomolgus Macaque
- Subchondral Bone Plate
- Remodelling Index