Microarchitectural alterations in arthritic subchondral bone

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

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

In this thesis, a general review on subchondral bone was provided. This reviewsummarized basic features of subchondral bone. Main risk factors influencingsubchondral bone integrity were described. Moreover, we focused on the abnormalchanges of subchondral bone in OA, and provided an overview of their potentialcontribution 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 currentstudy, we observed a significant difference between the superior STB and deepertrabecular bone (DTB) in OA. Compared to DTB, STB showed more scleroticmicroarchitecture, more active bone remodelling and higher frequency of bone cysts.This may be due to the distinct biomechanical and biochemical functions between thesetwo structures.

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

SBP provides structural support and significant mechanical function by transmittingloads 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 theabnormal alterations in STB observed in the previous study, we undertook a furtherinvestigation for the relationship between SBP integrity and the homeostasis ofunderlying STB in OA. Our study showed that, STB with full-thickness breach of SBPexhibited more sclerotic microarchitecture, higher bone remodeling level and higherSBCs frequency, as compared to those with partial-thickness breach of SBP. A mixedpathology was detected within SBCs, including fibrous tissue, abnormal blood vessels,fibrocartilaginous tissue, hyaline cartilaginous tissue, remnant bone fragments andadipose tissue. Our data indicated that SBP integrity is closely associated with thehomeostasis of underlying STB in the progression of OA. SBP may act as abiomechanical and biochemical shield between the synovial space and STB.

In contrast to the wealth of studies concerning subchondral bone in primary OA, thealterations of subchondral bone in secondary OA remain poorly acknowledged. Toinvestigate subchondral bone alterations in the subset of secondary OA withhomogenous biomechanics aetiology, we collected subchondral bone specimens infemoral heads from patients with OA secondary to hip dysplasia (HD-OA). In thecurrent study, the weight-bearing subchondral bone showed more sclerotic microarchitecture and more active bone remodeling in HD-OA, compared toosteoporosis (OP). In the non-weight-bearing region, the two diseases shared similarmicroarchitecture characteristics, but more active bone remodeling was detected inHD-OA. Distinct regional difference was only observed in HD-OA. In addition,HD-OA demonstrated more serious pathological alterations, including subchondralbone cyst, metaplastic cartilaginous tissue, bone marrow edema and fibrous tissue,especially in the weight-bearing region. Collectively, osteoarthritic deteriorations ofsubchondral bone induced by hip dysplasia spread throughout the whole joint, butexhibit region-dependent variations, with the weight-bearing region more seriouslyaffected. Biomechanical stress might exert a pivotal impact on subchondral bonehomeostasis.

Rheumatoid arthritis (RA) is a common chronic inflammatory joint disordercharacterized by persistent synovitis and juxta-articular bone erosion. However,subchondral bone, which lies distant from the cartilage-pannus junction, is an oftenneglected anatomic compartment in RA pathogenesis. Our data demonstrated that RAand OA showed similar microarchitecture patterns in both STB and DTB, despite STBin RA exhibiting higher bone resorption. In addition, there was no difference in SBCsfrequency between RA and OA. This may indicate that biomechanics exerts thedominant influence on the subchondral bone microarchitecture and remodeling in theload-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 substantiallyinvolved in the pathogenesis of OA and RA, with abnormal microarchitecture, boneremodelling and histopathological alterations. Maintenance of subchondral bonehomeostasis may represent a potential alternative therapeutic approach for theprophylaxis and treatment of OA and RA in the future.