Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model
- Gokhan DemirkiranAffiliated withDepartment of Orthopedics and Traumatology, Hacettepe University
- , Ozgur DedeAffiliated withDepartment of Orthopedics and Traumatology, Hacettepe University
- , Nadir YalcinAffiliated withDepartment of Orthopedic Surgery, Orthopedic Research Laboratory, University of California San Francisco
- , Ibrahim AkelAffiliated withKent Hospital
- , Ralph MarcucioAffiliated withDepartment of Orthopedic Surgery, Orthopedic Research Laboratory, University of California San Francisco
- , Emre AcarogluAffiliated withAnkara Spine Center Email author
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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.
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.
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).
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.
KeywordsScoliosis Animal model Bipedal mice Bone density Tamoxifen Raloxifene
- Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model
European Spine Journal
Volume 23, Issue 2 , pp 455-462
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- Springer Berlin Heidelberg
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- Animal model
- Bipedal mice
- Bone density
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- Author Affiliations
- 1. Department of Orthopedics and Traumatology, Hacettepe University, Ankara, Turkey
- 2. Department of Orthopedic Surgery, Orthopedic Research Laboratory, University of California San Francisco, San Francisco, CA, USA
- 3. Kent Hospital, Izmir, Turkey
- 4. Ankara Spine Center, Iran Caddesi 45/2, Kavaklidere, Ankara, 06700, Turkey