title: A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tiao
authors.initials: T
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Tong
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chandra
authors.affiliation: W.M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ, USA.
authors.forename: Shao-Yun
authors.initials: SY
authors.lastname: Hsu
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA ; Department of Orthopaedic Surgery, School of Medicine, Shihezi University , Shihezi, Xinjiang, China.
authors.forename: Haoruo
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Tseng
authors.affiliation: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania , PA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Levine
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA ; Department of Physical Medicine & Rehabilitation, Perelman School of Medicine, University of Pennsylvania and Translational Musculoskeletal Research Center, Philadelphia Veterans Affairs Medical Center , Philadelphia, PA, USA.
authors.forename: Yejia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Shi-Gui
authors.initials: SG
authors.lastname: Yan
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: X Sherry
authors.initials: XS
authors.lastname: Liu
authors.affiliation: W.M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Sun
authors.affiliation: W.M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ, USA.
authors.forename: Wise
authors.initials: W
authors.lastname: Young
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin