title: Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat.
abstract: BACKGROUND
  Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats.
  
  
  METHODS
  Posterolateral lumbar fusion (PLF) at L4-5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague-Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography.
  
  
  RESULTS
  Histological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae.
  
  
  CONCLUSIONS
  These results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar fusion.
authors.affiliation: Orthopaedic Research Institution of Hebei, Third Hospital of Hebei Medical University, Shijiazhuang, 050017, P.R. China.
authors.forename: Chang-Cheng
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Medical Research Center, North China University of Science and Technology, Tangshan, 063000, P. R. China. tfm9911316@163.com.
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Tian
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, No. 73 Jianshe South Rd., Tangshan, Hebei, 063000, P.R. China. 39094572@qq.com.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, No. 73 Jianshe South Rd., Tangshan, Hebei, 063000, P.R. China. 459350252@qq.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, No. 73 Jianshe South Rd., Tangshan, Hebei, 063000, P.R. China. 772866280@qq.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gou
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, No. 73 Jianshe South Rd., Tangshan, Hebei, 063000, P.R. China. agan_8898@qq.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063000, P. R. China. wangwenya7@126.com.
authors.forename: Wen-Ya
authors.initials: WY
authors.lastname: Wang
authors.affiliation: Orthopaedic Research Institution of Hebei, Third Hospital of Hebei Medical University, Shijiazhuang, 050017, P.R. China. shenyong2015@yeah.net.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Orthopaedic Research Institution of Hebei, Third Hospital of Hebei Medical University, Shijiazhuang, 050017, P.R. China. zhang_yingye@126.com.
authors.forename: Ying-Ze
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Orthopaedic Research Institution of Hebei, Third Hospital of Hebei Medical University, Shijiazhuang, 050017, P.R. China. zhliu130@sohu.com.|Department of Orthopedic Surgery, Affiliated Hospital of North China University of Science and Technology, No. 73 Jianshe South Rd., Tangshan, Hebei, 063000, P.R. China. zhliu130@sohu.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002116:Calcitonin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D055959:Intervertebral Disc Degeneration / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion / Q000009:adverse effects*; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D002116:Calcitonin