Microarchitectural alterations in arthritic subchondral bone

Guangyi Li

    Research output: ThesisDoctoral Thesis

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    Subchondral bone, consisting of subchondral bone plate (SBP) and underlying subchondral trabecular bone (STB), plays a pivotal role in the biomechanical and biochemical homeostasis of the joint. Subchondral bone is widely reported to contribute to the pathogenesis of various joint diseases.

    Osteoarthritis (OA) is the most prevalent joint disease, and the leading cause of pain and functional disability in the elderly population. Although OA has long been thought as a primary disorder of cartilage, subchondral bone is also actively involved in the initiation and progression of OA.

    In this thesis, a general review on subchondral bone was provided. This review summarized basic features of subchondral bone. Main risk factors influencing subchondral bone integrity were described. Moreover, we focused on the abnormal changes of subchondral bone in OA, and provided an overview of their potential contribution to OA pathogenesis.

    In normal joints, depth variation in the trabecular microarchitecture has been reported. However, depth variation in osteoarthritic joint is poorly investigated. In the current study, we observed a significant difference between the superior STB and deeper trabecular bone (DTB) in OA. Compared to DTB, STB showed more sclerotic microarchitecture, more active bone remodelling and higher frequency of bone cysts. This may be due to the distinct biomechanical and biochemical functions between these two structures.

    Age and gender have remarkable impacts on bone homeostasis. However, the influence of age and gender on bone metabolism in OA has been reported to be different from that in normal subjects. Consequently, we investigated age and gender dependency of microarchitecture and bone remodeling in both STB and DTB from the weight-bearing region of osteoarthritic femoral heads from 110 patients. There was no gender difference for microarchitecture and bone remodelling in STB, while distinct gender difference was detected in DTB. In both STB and DTB, no correlation between microarchitecture and age was found in both genders. However, bone remodeling of STB increased significantly with age in males, while bone remodeling parameters of DTB increased significantly with age in females. No age or gender preference was found in subchondral bone cysts (SBCs) frequency. The cyst volume fraction was correlated with neither age nor gender. To conclude, OA changed the normal age- and gender-dependence of bone homeostasis in joints, in a site-specific manner.

    SBP provides structural support and significant mechanical function by transmitting loads from cartilage towards STB. SBP is also infiltrated by a number of tiny channels, acting as a portal for biochemical interactions between cartilage and STB. Based on the abnormal alterations in STB observed in the previous study, we undertook a further investigation for the relationship between SBP integrity and the homeostasis of underlying STB in OA. Our study showed that, STB with full-thickness breach of SBP exhibited more sclerotic microarchitecture, higher bone remodeling level and higher SBCs frequency, as compared to those with partial-thickness breach of SBP. A mixed pathology was detected within SBCs, including fibrous tissue, abnormal blood vessels, fibrocartilaginous tissue, hyaline cartilaginous tissue, remnant bone fragments and adipose tissue. Our data indicated that SBP integrity is closely associated with the homeostasis of underlying STB in the progression of OA. SBP may act as a biomechanical and biochemical shield between the synovial space and STB.

    In contrast to the wealth of studies concerning subchondral bone in primary OA, the alterations of subchondral bone in secondary OA remain poorly acknowledged. To investigate subchondral bone alterations in the subset of secondary OA with homogenous biomechanics aetiology, we collected subchondral bone specimens in femoral heads from patients with OA secondary to hip dysplasia (HD-OA). In the current study, the weight-bearing subchondral bone showed more sclerotic microarchitecture and more active bone remodeling in HD-OA, compared to osteoporosis (OP). In the non-weight-bearing region, the two diseases shared similar microarchitecture characteristics, but more active bone remodeling was detected in HD-OA. Distinct regional difference was only observed in HD-OA. In addition, HD-OA demonstrated more serious pathological alterations, including subchondral bone cyst, metaplastic cartilaginous tissue, bone marrow edema and fibrous tissue, especially in the weight-bearing region. Collectively, osteoarthritic deteriorations of subchondral bone induced by hip dysplasia spread throughout the whole joint, but exhibit region-dependent variations, with the weight-bearing region more seriously affected. Biomechanical stress might exert a pivotal impact on subchondral bone homeostasis.

    Rheumatoid arthritis (RA) is a common chronic inflammatory joint disorder characterized by persistent synovitis and juxta-articular bone erosion. However, subchondral bone, which lies distant from the cartilage-pannus junction, is an often neglected anatomic compartment in RA pathogenesis. Our data demonstrated that RA and OA showed similar microarchitecture patterns in both STB and DTB, despite STB in RA exhibiting higher bone resorption. In addition, there was no difference in SBCs frequency between RA and OA. This may indicate that biomechanics exerts the dominant influence on the subchondral bone microarchitecture and remodeling in the load-bearing region which is far from the synovium, in both RA and OA.

    In summary, the studies in this thesis suggested that subchondral bone was substantially involved in the pathogenesis of OA and RA, with abnormal microarchitecture, bone remodelling and histopathological alterations. Maintenance of subchondral bone homeostasis may represent a potential alternative therapeutic approach for the prophylaxis and treatment of OA and RA in the future.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2015

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