title: Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model.
abstract: OBJECTIVE
  Previous work has suggested that progression of experimental scoliotic curves in pinealectomized chicken and bipedal C57BL6 mice models may be prevented and reversed with Tamoxifen treatment. Raloxifene is another Selective Estrogen Receptor Modulator (SERM) with estrogen agonist effects on bone and increases bone density but with fewer side effects on humans. To investigate whether scoliosis progression in bipedal C57Bl6 mice model could be prevented with SERM treatment and the mechanisms associated with this effect.
  
  
  METHODS
  Eighty C57BL6 mice were rendered bipedal and divided into Tamoxifen (TMX), Raloxifene (RLX) and control groups. TMX and RLX groups received orally administered TMX and RLX for 40 weeks. Anteroposterior X-ray imaging and histomorphometric analysis (at 20th and 40th weeks) were performed.
  
  
  RESULTS
  At 20th week, TMX and RLX groups displayed higher rates (p = 0.033, p = 0.029) and larger curve magnitudes (p = 0.018). At 40th week, curve rates were similar between the groups but the curve magnitudes in TMX and RLX groups were smaller (p = 0.001). Histomorphometry revealed that treated animals had higher trabecular density (p = 0.04), lower total intervertebral disc (p = 0.038) and growth plate volumes (p = 0.005) and smaller vertebral bodies (p = 0.016).
  
  
  CONCLUSIONS
  Treatment with TMX or RLX did not reduce the incidence of scoliosis but decreased the curve magnitudes at 40 weeks. The underlying mechanism associated with the decrease in curve magnitudes may be the early maturation of growth plates, thereby possible deceleration of the growth rate of the vertebral column and increase in bone density. RLX is as effective as TMX in preventing the progression of scoliotic curves in melatonin deficient bipedal mice.
authors.affiliation: Department of Orthopedics and Traumatology, Hacettepe University, Ankara, Turkey.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Demirkiran
authors.forename: Ozgur
authors.initials: O
authors.lastname: Dede
authors.forename: Nadir
authors.initials: N
authors.lastname: Yalcin
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Akel
authors.forename: Ralph
authors.initials: R
authors.lastname: Marcucio
authors.forename: Emre
authors.initials: E
authors.lastname: Acaroglu
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012600:Scoliosis / Q000188:drug therapy* / Q000473:pathology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride