Microarchitectural Alterations Of Subchondral Bone In Human Femoral Heads

OBJECTIVE: 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, including osteoarthritis(OA) and rheumatoid arthritis(RA). This study investigated age- and gender- related changes of microstructure and bone remodeling in subchondral bone in OA. This study also explored the relationship between breach of SBP and STB deterioration in OA. In addition, this thesis analyzed the differences in microarchitecture, bone remodeling and bone marrow pathology of subchondral bone in femoral heads from patients with OA secondary to hip dysplasia(HD-OA) and osteoporosis(OP). In the end, this study assessed the differences in microarchitecture and bone remodeling of subchondral bone in femoral heads from patients with RA and OA.METHODS: The first part: STB and deeper trabecular bone(DTB) were extracted in the load-bearing region of femoral heads from 110 patients with OA. Micro-CT and histomorphometry were performed to analyze microarchitectural and bone remodeling changes of all samples. The second part: Subchondral bone cylinders were extracted in the load-bearing region of femoral heads from 110 patients with late-stage OA after hip replacement surgery. SBP integrity, STB microarchitecture and subchondral bone cysts(SBCs) were examined by micro-CT. Bone remodeling in STB and pathological changes inside SBCs were assessed by histology. The third part: Subchondral bone specimens were extracted from both weight-bearing and non-weight-bearing regions of femoral heads from 20 patients with HD-OA and 20 patients with osteoporotic femoral neck fracture, during hip replacement surgery. Micro-CT and histologic examination were performed to assess the microarchitecture, bone remodeling and bone marrow pathology. The fourth part: Peri-articualr bone samples, including STB and DTB were extracted from the load-bearing region of femoral heads from 20 patients with RA and 40 patients with OA during hip replacement surgery. Micro-CT, histomorphometry and backscatter scanning electron microscopy were performed to assess microarchitecture and bone histology parameters.RESULTS: The first part: There were distinct differences in microarchitecture and bone remodeling between STB and DTB. OA changed the normal ageand gender-dependence of bone homeostasis in joints, in a site-specific manner. The second part: SBP integrity is closely associated with the homeostasis of underlying STB in the progression of OA. The third part: Osteoarthritic deterioration of subchondral bone induced by hip dysplasia may spread throughout the whole joint, but exhibit a region-dependent variation, with the weight-bearing region more seriously affected. The fourth part: Apart from higher bone resorption in the general subchondral bone of RA samples, the peri-articular bone exhibited similar microarchitectural and bone remodeling characteristics in RA and OA.CONCLUTIONS: 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.