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Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model

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Abstract

Purpose

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.

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Acknowledgments

This study was supported by research grants from the “Yves Cotrel Foundation”, Paris, France.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Orthopedics and Traumatology, Hacettepe University, Ankara, Turkey

    Gokhan Demirkiran & Ozgur Dede

  2. Department of Orthopedic Surgery, Orthopedic Research Laboratory, University of California San Francisco, San Francisco, CA, USA

    Nadir Yalcin & Ralph Marcucio

  3. Kent Hospital, Izmir, Turkey

    Ibrahim Akel

  4. Ankara Spine Center, Iran Caddesi 45/2, Kavaklidere, Ankara, 06700, Turkey

    Emre Acaroglu

Authors
  1. Gokhan Demirkiran
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  2. Ozgur Dede
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  3. Nadir Yalcin
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  4. Ibrahim Akel
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  5. Ralph Marcucio
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  6. Emre Acaroglu
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Corresponding author

Correspondence to Emre Acaroglu.

Additional information

First three authors (Drs. Demirkiran, Dede and Yalcin) have equally contributed to the research project as well as the preparation of the manuscript. Their present order of appearance is arbitrary in this sense.

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Demirkiran, G., Dede, O., Yalcin, N. et al. Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model. Eur Spine J 23, 455–462 (2014). https://doi.org/10.1007/s00586-013-3072-2

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  • DOI: https://doi.org/10.1007/s00586-013-3072-2

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