Liver fibrosis reflects tissue scarring in the liver due to the accumulation of excessive extracellular matrix in response to chronically persistent liver injury. Hepatocyte cell death can trigger capillarization of liver sinusoidal endothelial cells, stimulation of immune cells including macrophages and Kupffer cells, and activation of hepatic stellate cells (HSCs), resulting in progression of liver fibrosis. Liver cirrhosis is the terminal state of liver fibrosis and is associated with severe complications, such as liver failure, portal hypertension, and liver cancer. Nevertheless, effective therapy for cirrhosis has not yet been established, and liver transplantation is the only radical treatment for severe cases. Studies investigating HSC activation and regulation of collagen production in the liver have made breakthroughs in recent decades that have advanced the knowledge regarding liver fibrosis pathophysiology. In this review, we summarize molecular mechanisms of liver fibrosis and discuss the development of novel anti-fibrotic therapies.

Liver fibrosis reflects tissue scarring in the liver due to the accumulation of excessive extracellular matrix in response to chronically persistent liver injury. Hepatocyte cell death can trigger capillarization of liver sinusoidal endothelial cells, stimulation of immune cells including macrophages and Kupffer cells, and activation of hepatic stellate cells (HSCs), resulting in progression of liver fibrosis. Liver cirrhosis is the terminal state of liver fibrosis and is associated with severe complications, such as liver failure, portal hypertension, and liver cancer. Nevertheless, effective therapy for cirrhosis has not yet been established, and liver transplantation is the only radical treatment for severe cases. Studies investigating HSC activation and regulation of collagen production in the liver have made breakthroughs in recent decades that have advanced the knowledge regarding liver fibrosis pathophysiology. In this review, we summarize molecular mechanisms of liver fibrosis and discuss the development of novel anti-fibrotic therapies.

Objectives: The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women. Methods: Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters. Results: Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure. Conclusions Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HRpQCT parameters in the tibia than in the radius, the magnitude of association is modest.

Objectives: The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women. Methods: Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters. Results: Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure. Conclusions Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HRpQCT parameters in the tibia than in the radius, the magnitude of association is modest.

Objectives: Physical activity to maintain bone mass and strength is important for hip fracture prevention. We aim to investigate the relationship between physical performance/activity status and bone mineral density (BMD)/hip structural analysis (HSA) parameters among postmenopausal women in Japan. Methods: Sixty-two postmenopausal women diagnosed with osteoporosis (mean age: 72.61 ± 7.43 years) were enrolled in this cross-sectional observational study. They were evaluated for BMD and HSA in the proximal femur by dual-energy X-ray absorptiometry and underwent several physical performance tests, the Geriatric Locomotive Function Scale of 25 questions (GLFS-25). Principal component analysis (PCA) was used to summarize data on the BMD/HSA parameters. Partial correlation analysis, multiple regression analysis, and structural equation modeling (SEM) were performed to investigate the relationship between physical performance/activity status and BMD/HSA parameters of the proximal femur. Results: In a partial correlation analysis adjusted for age and body mass index (BMI), GLFS-25 scores were correlated with HSA parameter (|r| = 0.260–0.396, P < 0.05). Principal component 1 (PC1) calculated by PCA was interpreted as more reflective of bone strength based on the value of BMD/HSA parameters. The SEM results showed that the model created by the 3 questions (Q13, brisk walking; Q15, keep walking without rest; Q20, load-bearing tasks and housework) of the GLFS-25 had the best fit and was associated with the PC1 score (β = −0.444, P = 0.001). Conclusions The GLFS-25 score was associated with the BMD/HSA parameter, which may reflect the bone strength of the proximal femur as calculated by PCA.

Wide resection of malignant bone and soft tissue tumors of the extremities may require resection of muscles, which correspondingly impairs limb movements. We describe a 67-year old man with a malignant soft tissue tumor of the right upper arm. Preoperatively, there was no impairment of right upper extremity function. The patient underwent wide resection of the tumor and triceps muscle. Postoperative rehabilitation included range of motion exercises, residual muscle strength exercises, and activities of daily living (ADL) exercises. One week postoperatively, the patient could independently perform the ADL exercises. Two weeks postoperatively, the patient scored 2 during manual muscle testing (MMT) for elbow extension, indicating a complete range of motion in a gravity-eliminated position. However, the patient could not raise the arm without bending it. Considering the needs of the patient, we prescribed an elbow extension brace to support the upper limb while being raised. With this brace, the patient was able to sustain elbow extension during upper limb elevation. Three months postoperatively, the patient's elbow joint extension remained MMT 2, grip strength was 28 kg, and the International Society of Limb Salvage and Musculoskeletal Tumor Society score was 76.7％．Although the triceps muscle was resected, there was no problem with the patient's ADL. However, the patient could not maintain elbow extension in an anti-gravity position while raising the upper limb. In such cases, prescribing an elbow brace may be useful.

Wide resection of malignant bone and soft tissue tumors of the extremities may require resection of muscles, which correspondingly impairs limb movements. We describe a 67-year old man with a malignant soft tissue tumor of the right upper arm. Preoperatively, there was no impairment of right upper extremity function. The patient underwent wide resection of the tumor and triceps muscle. Postoperative rehabilitation included range of motion exercises, residual muscle strength exercises, and activities of daily living (ADL) exercises. One week postoperatively, the patient could independently perform the ADL exercises. Two weeks postoperatively, the patient scored 2 during manual muscle testing (MMT) for elbow extension, indicating a complete range of motion in a gravity-eliminated position. However, the patient could not raise the arm without bending it. Considering the needs of the patient, we prescribed an elbow extension brace to support the upper limb while being raised. With this brace, the patient was able to sustain elbow extension during upper limb elevation. Three months postoperatively, the patient’s elbow joint extension remained MMT 2, grip strength was 28 kg, and the International Society of Limb Salvage and Musculoskeletal Tumor Society score was 76.7％．Although the triceps muscle was resected, there was no problem with the patient’s ADL. However, the patient could not maintain elbow extension in an anti-gravity position while raising the upper limb. In such cases, prescribing an elbow brace may be useful.