Abstract
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.
