title: Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats.
abstract: We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae.
  
  
  BACKGROUND
  The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats.
  
  
  METHODS
  We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3-4 and L5-6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5-6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression.
  
  
  RESULTS
  At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats.
  
  
  CONCLUSIONS
  Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.
authors.affiliation: Medical Research Center, Affiliated Hospital of Hebei United University, Tangshan, People's Republic of China.
authors.forename: F-m
authors.initials: FM
authors.lastname: Tian
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University, No. 73 Jianshe South Rd, Tangshan, 063000, Hebei, People's Republic of China.
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Pathology of Basic Medical Sciences School, Hebei United University, Tangshan, People's Republic of China.
authors.forename: W-y
authors.initials: WY
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University, No. 73 Jianshe South Rd, Tangshan, 063000, Hebei, People's Republic of China.
authors.forename: S-y
authors.initials: SY
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University, No. 73 Jianshe South Rd, Tangshan, 063000, Hebei, People's Republic of China.
authors.forename: H-p
authors.initials: HP
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Y-z
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University, No. 73 Jianshe South Rd, Tangshan, 063000, Hebei, People's Republic of China. zhliu130@sohu.com.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001851:Bone Diseases, Metabolic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002116:Calcitonin / Q000627:therapeutic use*; D024043:Collagen Type II / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D010052:Ovariectomy; D013314:Stress, Mechanical; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D050071:Bone Density Conservation Agents; D024043:Collagen Type II; C028815:salmon calcitonin; D002116:Calcitonin; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1
keywords: Biomechanics; Intervertebral disk degeneration; Micro-computed tomography; Osteopenia; Salmon calcitonin