| Background:With the incidence of osteoporosis (OP) increasing rapidly as the population ages, there are currently 200 million osteoporosis patients worldwide. OP-related fractures have become a formidable public health threat due to the high mortality and morbidity. Early screening and interventions have been proved to be effective strategies in fracture prevention for the population at risk. The currently diagnosis and assessment of osteoporosis and prediction of fracture risk mainly relies on the bone mineral density (BMD) measurements using dual energy X-ray absorptiometry (DXA). However, it has been proved that the obtained performance is being unsatisfied. Previous studies reported that during disease progression of OP, pathological deterioration would lead a heterogeneous distribution of bone structure, which could be observed in composition, trabecular microstructure and mechanical property. However, few studies have been carried out on the characteristics and quantitative evaluation of the above mentioned bone structure heterogeneity (BSH) in OP patients. The association between BSH and the severity of OP or the fracture risk remains unknown. A complete evaluation of BSH would provide an additional value for the evaluation of OP, benefiting the diagnosis, severity assessment and fracture risk estimation.Purpose:(1) To explore the characteristic of bone structure in osteoporotic femoral head (FH) to achieve the quantitative evaluation of BSH, and to assess the association between BSH and severity of OP. (2) To extend the concept of BSH from femoral head to proximal femur and calculate BMD heterogeneity (BMD-H) by DXA tests, and to assess the association between BMD-H and fracture risk and the potential clinical utility of BMD-H.Methods:(1) A novel method for accurately locating and trephining trabeculae in FH was developed using a computed tomography (CT) and 3D-printed technology, offering a methodological support for the comparison of bone-tissue properties of different individuals. (2) DXA, quantitative computed tomography (QCT), Micro-CT and biomechanical test were used to measure BMD, microstructural parameters of trabecular bone (Tb.N, Tb.Th, Tb.Sp, etc) and mechanical properties of FH. BSH was calculated using BMD and the association between BSH and anatomical location or severity of OP was investigated. (3) A case-control study among osteoporotic fracture (OPHF) patients and non-osteoporosis (NOP) patients was performed to examine the association between BMD-H of the proximal femur, calculated using non-invasive measurement of hip DXA, and BMD or OPHF risk or geometric and mechanical parameters of the hip. The association of BMD-H with OPHF risk was preliminary discussed and the potential clinical utility of BMD-H was also assessed.Results:(1) Osteoporotic FH showed a heterogeneous structure. The center part of FH was not sensitive during the progression of OP, which could be used as reference, while the up part of PCT, the main weight-bearing surface, was sensitive to reflect the amount of remaining bone and could be used as indicator. Then the quantitative assessment of BSH could be obtained with using data from the above-mentioned parts. (2) In patients with severe OP, BSH in the PCT but not in the NWB area could reflect the bone resorption of FH. (3) The value of BSH was greatly influenced by the spatial deviation of extracting trabecular column. After further controlling the anatomical factors, BSH in the PCT was found to be significantly associated with severity of OP (Pearson’s correlation:-0.29～-0.70, P<0.05). (4) The case-control study indicated a generalizability of the association between BSH and OP severity. BMD-H of the proximal femur was significantly associated with the OP severity (Pearson’s correlation:-0.32～-0.46, P＜0.001). Further analysis revealed that BMD-H was an effect modifier for BMD. The BMD-H with high values demonstrated that the association strength between BMD and OPHF risk was higher (OR 14.04, P＜0.001), compared with the BMD-H with middle values (OR 3.08, P<0.001) and low values (OR 4.40, P＜0.001). Combing BMD-H with BMD would provide a more precise evaluation of OP severity and OPHP risk.Conclusion:(1) A generalizability of the association between BSH and OP severity exists in OP patients, which has been validated in FH and proximal femur in this study. (2) In patients with severe OP, after excluding the impact of the anatomical factors, BSH of FH can reflect the severity of OP from a perspective of structure variation. (3) The case-control study indicated that BMD-H of the proximal femur is closely related to the severity of OP. BMD-H is an effect modifier for BMD. Combining BMD-H with BMD would provide a more precise evaluation of OP severity and OPHP risk. |
PDF Full Text Request