Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective treatment.Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To ...Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective treatment.Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical analyses.At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.展开更多
Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorpti...Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass.While they are effective to prevent further bone loss,there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity.PTH,the only FDA-approved anabolic treatment for osteoporosis,greatly stimulates bone formation.Combined therapy of anti-resorptive treatments,such as alendronate(ALN),and PTH have been proposed and are expected to further increase bone mass.However,studies show conflicting results regarding the effectiveness展开更多
基金supported by the National Institutes of Health(R01DK095803 to LQ, 1K08HD049598 to YZ)Penn Center for Musculoskeletal Disorders P30AR050950(NIAMS/NIH)+1 种基金ASBMR Junior Faculty Osteoporosis Basic Research Award(to LQ)NIH/NIAMS R03-AR065145(to XSL)
文摘Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective treatment.Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical analyses.At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.
基金supported by McCabe pilot award and the Penn Center for Musculoskeletal Disorders(NIH/NIAMS P30AR050950)
文摘Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass.While they are effective to prevent further bone loss,there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity.PTH,the only FDA-approved anabolic treatment for osteoporosis,greatly stimulates bone formation.Combined therapy of anti-resorptive treatments,such as alendronate(ALN),and PTH have been proposed and are expected to further increase bone mass.However,studies show conflicting results regarding the effectiveness
