Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed.

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Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes

Early OA primarily affects articular cartilage and involves the entire joint, including the subchondral bone, synovial membrane, menisci and periarticular structures. The aim of this review is to highlight the molecular basis and histopathological features of early OA. Selective review of literature. Risk factors for developing early OA include, but are not limited to, a genetic predisposition, mechanical factors such as axial malalignment, and aging. In early OA, the articular cartilage surface is progressively becoming discontinuous, showing fibrillation and vertical fissures that extend not deeper than into the mid-zone of the articular cartilage, reflective of OARSI grades 1.0–3.0. Early changes in the subchondral bone comprise a progressive increase in subchondral plate and subarticular spongiosa thickness. Early OA affects not only the articular cartilage and the subchondral bone but also other structures of the joint, such as the menisci, the synovial membrane, the joint capsule, ligaments, muscles and the infrapatellar fat pad. Genetic markers or marker combinations may become useful in the future to identify early OA and patients at risk. The high socioeconomic impact of OA suggests that a better insight into the mechanisms of early OA may be a key to develop more targeted reconstructive therapies at this first stage of the disease. Systematic review, Level II.

Biological aspects of early osteoarthritis

Osteoarthritis (OA), the most common rheumatic disease, is characterized by joint-space narrowing due to progressive cartilage degradation and alterations in subchondral bone and the synovial membrane. These articular disturbances can have severe consequences, including pain, disability and loss of joint architectural integrity. Although the aetiology of OA is not understood, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by damage-associated molecules are thought to be involved. In this Review, we examine the relationship between Toll-like receptor 4 (TLR4) and OA in cartilage as well as in other OA-affected tissues, such as subchondral bone and synovium. We also discuss the different TLR4 agonists associated with OA and their effects in joint tissues. Finally, we describe existing and novel strategies that might be used to develop TLR4-specific disease-modifying OA drugs (DMOADs).

TLR4 signalling in osteoarthritis--finding targets for candidate DMOADs.

There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA. Level of evidence IV.

Early osteoarthritis of the knee.

In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix (ECM), the composition of which varies as a function of the tissue, the degree of maturation and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the "3Rs" guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas and liver will be presented.

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Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models.

https://www.oarsijournal.com/article/S1063-4584(10)00387-0/pdf

In vivo structural analysis of subchondral trabecular bone in osteoarthritis of the hip using multi-detector row CT.

Summary
Subchondral trabecular bone structure was analyzed in knee osteoarthritis (OA) patients using 3-T MRI to investigate structural features of subchondral trabecular bone of knee OA. With OA progression, osteoporotic changes were observed in the lateral joint, showing a higher correlation than sclerotic changes in the medial joint.

Osteoporotic changes of subchondral trabecular bone in osteoarthritis of the knee: a 3-T MRI study.

Purpose
Tibial condylar valgus osteotomy (TCVO) is a type of opening-wedge high tibial osteotomy for advanced medial knee osteoarthritis (OA) with subluxated lateral joint. We report the concept, the current surgical technique with a locking plate, and the short-term clinical and radiological results of this procedure.

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Tibial condylar valgus osteotomy (TCVO) for osteoarthritis of the knee: 5-year clinical and radiological results.

We analyzed the microstructure and degree of mineralization of the subchondral trabecular bone in hip osteoarthritis (OA) using synchrotron radiation computed tomography (SRCT) to identify the relationship between bone structure and bone turnover Subchondral bone samples were extracted from femoral heads of 10 terminal-staged hip OA patients The SRCT scan was performed at 30 keV energy and 59 µm voxel size Trabecular bone structure, bone cyst volume, and the degree of trabecular bone mineralization were measured, and correlations between bone structure and the degree of mineralization were analyzed In addition, the trabecular bone was divided into the area immediately surrounding the bone cyst and the remaining area, and they were compared The average cyst volume fraction in the whole region was 318%, and the bone volume fraction in the bone region was 556% Cyst volume was the only structural parameter that had a significant correlation with the degree of mineralization The degree of mineralization was diminished when the bone cyst was larger (r = -081, p = 0004) The trabecular bone immediately surrounding the bone cyst had a lower degree of mineralization when compared with the remaining trabecular bone (p = 0008) In the bone sclerosis of OA subchondral bone, there are many large and small bone cysts, which are expected to play a significant part in the high bone turnover of OA

https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1002/jbmr.1609

Ko Chiba

Papers

In vivo structural analysis of subchondral trabecular bone in osteoarthritis of the hip using multi-detector row CT.

Osteoporotic changes of subchondral trabecular bone in osteoarthritis of the knee: a 3-T MRI study.

Tibial condylar valgus osteotomy (TCVO) for osteoarthritis of the knee: 5-year clinical and radiological results.

Relationship between microstructure and degree of mineralization in subchondral bone of osteoarthritis: A synchrotron radiation µCT study

Heterogeneity of bone microstructure in the femoral head in patients with osteoporosis: An ex vivo HR-pQCT study