Serum Amyloid A Correlates With the Osteonecrosis of Femoral Head by Affecting Bone Metabolism

Osteonecrosis of femoral head (ONFH) is a progressive hip joint disease without disease-modifying treatment. Lacking understanding of the pathophysiological process of ONFH has become the humper to develop therapeutic approach. Serum amyloid A (SAA) is an acute phase lipophilic protein during inflammation and we found that SAA is increased for the first time in the serum of ONFH patients through proteomic studies and quantitatively verified by ELISA. Treating rBMSCs with SAA inhibited the osteogenic differentiation via Wnt/β-catenin signaling pathway deactivation and enhanced the adipogenic differentiation via MAPK/PPARγ signaling pathway activation. Finally, bilateral critical-sized calvarial-defect rat model which received SAA treated rBMSCs demonstrated reduction of bone formation when compared to untreated rBMSCs implantation control. Hence, SAA is a vital protein in the physiological process of ONFH and can act as a potential therapeutic target to treat ONFH.

Differences in the Microarchitectural and Histomorphologic Characteristics Between Glucocorticoid-induced Osteonecrosis of Femoral Head and Alcohol-induced Osteonecrosis of Femoral Head

AimsTo analyze microarchitecture and histomorphology characteristics of different regions in femoral heads from patients with glucocorticoid-induced osteonecrosis of femoral head (GIONFH) and alcohol-induced osteonecrosis of femoral head (AIONFH). MethodsPatients diagnosed with GIONFH and AIONFH were recruited. Femoral heads were obtained after total hip replacement. Micro-CT was applied to evaluate the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology were then performed to assess histopathological alterations and bone remodeling levels. Results42 GIONFH patients (50 hips) and 43 AIONFH patients (50 hips) anticipated in the study. In the necrotic region, most of the microarchitectural parameters did not differ significantly between GIONFH and AIONFH, whereas both the reactive interface and normal region illustrated significant differences in the microstructure and histomorphometry. The reactive interface and normal region exhibited a less sclerotic microarchitecture, but a higher bone remodeling level in GIONFH as compared with AIONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GIONFH. ConclusionsAlthough these two subtypes of ONFH shared similar microarchitecture and pathological features in the necrotic region, GIONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region.