Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA ; Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, China.
Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA ; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, China.
Bone Res. 2015 Oct 27;3:15028. doi: 10.1038/boneres.2015.28. eCollection 2015.
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 (µCT), 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.
脊髓损伤（SCI）导致的骨丢失是最严重的骨质疏松症，目前尚无有效的治疗方法。过去的动物研究主要集中在急性阶段使用青少年啮齿动物的长骨上。为了模拟人类患者的慢性 SCI，我们对 SCI 后成年大鼠的轴向和附肢骨的长期结构和力学变化进行了全面分析。在该实验中，4 月龄的 Fischer 344 雄性大鼠接受了临床相关的 T13 挫伤损伤。16 周后，从这些大鼠和额外的非手术大鼠收集亚损伤股骨、胫骨和 L4 椎体、超损伤肱骨以及血液，用于微计算机断层扫描（µCT）、微有限元、组织学和血清生化分析。在骨小梁部位，SCI 后亚损伤长骨的骺端出现了骨结构和机械性能的极度丧失，而同一骨骼的软骨下部分损伤则较轻。亚损伤 L4 椎体的骨量和强度也明显降低，但超损伤肱骨没有。在皮质部位，SCI 导致了亚损伤和超损伤长骨的结构和强度损伤。这些变化伴随着成骨细胞数量和活性的减少以及破骨细胞数量和活性的增加。总之，我们的研究揭示了 SCI 对骨骼的特定部位的影响，并证实了 SCI 慢性阶段骨形成持续抑制和骨吸收增加。
