Periarticular Bone Changes in Osteoarthritis
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Keywordsosteoarthritis subchondral bone osteoclast micro-SPECT micro-CT
Osteoarthritis (OA) can be considered an organ failure with pathological aspects in cartilage, bone, ligaments, and synovium. Altogether, these tissue changes can result in pain and immobilization—a failure of the joint. It is well regarded that OA is a complex multifactorial disease with many risk factors and different etiological pathways that all lead to an apparently similar end stage. Bony changes are clearly observed in advanced OA. However, little understanding exists on the role of these changes, whether they are a consequence of cartilage damage or precede this damage and maybe play an important role in the etiological process. Even more important is the issue of pain. Radiological scores of OA do not match well with pain and mobility scores, which questions the value of these scoring systems. It seems that we do not assess the most relevant parameters. Evaluation of conventional and new radiographic parameters is still an extensive part of the OA research field. We may have overlooked certain (subtle) parameters that can be extracted from x-rays, but other imaging modalities such as MRI, CT, or SPECT might better represent OA in a clinically relevant manner.
Subchondral Bone Adaptation in Osteoarthritis
Another interesting hypothesis came from the work of Westacott et al. , who found that bone cells from OA patients can adversely influence cartilage metabolism. This provided a hint that the increased subchondral bone activity in OA joints can lead to cartilage degeneration. Of course, this hypothesis requires diffusion of harmful agents between the subchondral bone compartment and the cartilage, which might be difficult if the mineralized cartilage and subchondral plate are relatively dense. To further investigate the role of subchondral bone in OA, we decided to first investigate the cascade of events in subchondral bone during the progression of OA in animal models using micro-CT for in vivo evaluations at various time points after induction of OA.
Observations from a Murine Model of Osteoarthritis
Surprisingly, higher bone turnover is an extremely fast response in the MIA model, contrary to the idea that MIA directly targets the cartilage, thereby inducing OA. This finding could be interpreted as the bone alteration occurring first. However, care must be taken with this interpretation. What we call “first” also relates to how much we can see with our imaging and/or histological methods. The bone SPECT scan is an extremely sensitive tool for measuring a bone response, and the cartilage might have been responsive to the MIA trigger at the 2-day time point as well, but maybe the histology was not sensitive enough to show it.
The animal models and the imaging tools provide a powerful combination for studying OA. What did we learn from the current approaches? It has been known for some years that subchondral bone is a highly adaptive tissue, and changes in subchondral bone can be accurately visualized and quantified by CT  and scintigraphy  even in a clinical setting. Animal CT and SPECT have been improved in the last decade to higher resolutions [3, 12], enabling refined in vivo evaluation in small animal research. Besides evaluations of subchondral bone and cartilage with the microimaging modalities, SPECT/CT can image macrophage activation as well . With repetitive imaging of animals, we will learn the precise sequence of events that occur in the various tissues of the diseased joint. The bone scan analyses, with its fast (2 days) response in bone turnover in the MIA OA model, substantiate the often suggested crosstalk between the bone and cartilage compartments. In the different animal models, this sequence of events might be different; in one model, the problems might start in the cartilage, whereas in another model the bone might be triggered first. Each model might expose a different etiological pathway, similar to the differences in OA etiology in humans. Hopefully, these new tools will elucidate concepts and targets that help us in the design of new therapeutic interventions for OA.
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The author certifies that his institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
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- 6.Müller-Gerbl M. The subchondral bone plate. Adv Anat Embryol Cell Biol 141:III-XI, 1–134, 1998.Google Scholar
- 8.Piscaer TM, Müller C, Mindt TL, Lubberts E, Verhaar JA, Krenning EP, Schibli R, De Jong M, Weinans H. Imaging of activated macrophages in experimental osteoarthritis using folate-targeted animal single-photon-emission computed tomography/computed tomography. Arthritis Rheum 63:1898–907, 2011PubMedCrossRefGoogle Scholar