Introduction. Forelimb and tail amputations of 3-week-old C57BL/6 mice are known to yield spinal curves similar to adolescent idiopathic scoliosis (AIS). Our previous work showed that tamoxifen produces a significant decrease in severity of these curves. Vertebral osteoporosis was thought to be related to AIS. Interestingly, a histological pilot study has shown that scoliotic mice given tamoxifen were less osteoporotic than were controls. Raloxifene is an oestrogen receptor modulator (SERM) similar to tamoxifen with a more specific effect on bone and is commonly used to treat osteoporosis. We aimed to study and compare the effects of tamoxifen and raloxifene on the rate and magnitude of scoliosis on a C57BL/6 mice model. Methods. 90 female 3-week-old C57BL/6 mice underwent amputations of forelimbs and tails. 78 were available for analysis and were grouped as control (no medications; n=24), TMX group (10 mg tamoxifen/L drinking water; n=30), and RLX group (10 mg raloxifene/L drinking water; n=241). Seven mice from each group (including scoliotic ones) were killed for histological study at week 20 after posteroanterior (PA) scoliosis radiograph examinations. The rest were killed at the end of week 40 after PA radiographs were obtained. Radiographs were assessed for presence and magnitude of spinal curves. Results. Week 20 analysis showed that lower thoracic curve rate (LTr) was higher in RLX group (p=0·029) and thoracolomber rate (TLr) was higher in TMX group (p=0·33) than in the control group. TMX group had higher upper thoracic (UT) curve magnitudes than did the control group (p=0·021). Week analysis showed similar curve rates in all groups. The RLX group had significantly decreased upper (p<0·0001) and lower (p=0·014) thoracic curve magnitudes compared with the control group. The TMX group had significantly lower UT curve magnitudes than did the control group (p=0·014). Conclusions. Raloxifene is shown to be as effective as tamoxifen in decreasing the magnitude of spinal deformities in C57BL/6 mice model. These results suggest that SERMs might be useful to prevent progression of scoliotic curves. Models of higher animals may be warranted

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

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