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EFFECT OF THE TIMING OF TAXOXIFEN ADMINISTRATION ON C57BL/6 MICE SCOLIOSIS

British Scoliosis Research Foundation (BSRF)



Abstract

Introduction

Previous work has shown that C57BL/6 mice develop scoliosis when rendered bipedal. Our previous work suggested that tamoxifen (TMX) might change the natural course of scoliosis when administered before scoliotic curves develop. We analysed whether the incidence of scoliosis or the magnitude of curves may be decreased by the administration of tamoxifen after curves are observed.

Methods

20 female, 3-week-old C57BL/6 mice underwent amputations of forelimbs and tails at 3 weeks, 18 of which were included in analyses. Posteroanterior scoliosis radiographs were obtained at week 20, and scoliotic curves were recorded. After week 20, all mice received 10 mg TMX per L of daily water supply for 20 weeks. The course of deformities in this group (week 20 group) was compared with that of previous study groups (receiving TMX from week 3; week 3 group).

Results

At week 20, overall, upper thoracic (UT), thoraco-lumbar (TL), and double curve scoliosis rates were similar in both groups, but the thoracic (T) scoliosis rate was lower in the week 3 group. At week 40, although T, TL, and double curve scoliosis rates were similar between groups, overall rate and the rates of UT scoliosis were significantly lower in week 3 group (table). We recorded no significant change of curve rates in week 20 group apart from the TL rate, which showed a significant increase (p=0·025). Mean Cobb angles were similar in both study groups (p>0·05) at 20 and 40 weeks.

Conclusions

This study has shown that TMX administered after scoliotic changes are observed seems to be less effective compared with prior TMX protocol in C57BL/6 mice model. This information is important for the planning of possible pharmacological intervention in human beings.