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CALMODULIN ANTAGONISTS DECEASE THE RATE OF PROGRESSION AND SEVERITY OF SCOLIOSIS: A MELATONIN-DEFICIENT C57BL/6 MODEL

British Scoliosis Research Foundation (BSRF)



Abstract

Introduction

Calmodulin probably has a regulatory role in muscle contraction and its antagonism may decrease the magnitude and progression of scoliosis. A separate study has shown that tamoxifen (TMX), a known antagonist, is effective in altering the natural history in an avian model; however, whether the same effect is conceivable in mammals is unknown.

We aimed to analyse whether the natural course of scoliosis in mice may be altered by the administration of TMX.

Methods

60 female, 3-week-old, C57BL/6 mice underwent amputations of forelimbs and tails. 57 mice were assigned to three groups: control group, no medications; TMX group, 10 mg TMX/L drinking water; and combined group, 10 mg TMX plus 10 mg trifluoperazine (TFP)/L drinking water. PA scoliosis radiographs were taken at 20 and 40 weeks and evaluated for presence and magnitude of spinal curves.

Results

Four mice were lost to follow-up in the TMX group. Overall scoliosis rate was significantly lower in the TMX group (33%) than in the control (90%) and combined (68%) groups (p=0·001) at week 40. Similarly, upper thoracic scoliosis rate was lower in the TMX group (27%) than in control (74%) and combined (47%) groups (p=0·01). The thoracic scoliosis rate was also lower in the TMX group (7%) group than in control (63%) and combined (26%) groups (p=0·001). Combined drug group had lower thoracic and lumbar Cobb angles (17·50° [□}3·45]) than did the control group (29·40° [□}5·98]; p=0·031). Furthermore, double curve incidence at week 40 was lower in TMX group (12%) than in control (74%) and combined (47%) groups (p=0·001). Triple curve incidence was lower in combined (0%) and TMX (6%) groups than in the control group (15%), but this result was not significant (p=0·167).

Conclusions

TMX effectively decreased the incidence and magnitude of the scoliotic curves in C57BL/6 mice scoliosis model. This is a novel finding, and could be very important in opening a pathway for the conservative treatment of idiopathic scoliosis by oral drugs.