Demirkiran Gokhan, Dede Ozgur, Yalcin Nadir, Akel Ibrahim, Marcucio Ralph, Acaroglu Emre
Department of Orthopedics and Traumatology, Hacettepe University, Ankara, Turkey.
Eur Spine J. 2014 Feb;23(2):455-62. doi: 10.1007/s00586-013-3072-2. Epub 2013 Oct 18.
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.
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.
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).
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.
先前的研究表明,他莫昔芬治疗可预防和逆转松果体切除的鸡和双足C57BL6小鼠模型中实验性脊柱侧凸曲线的进展。雷洛昔芬是另一种选择性雌激素受体调节剂(SERM),对骨骼具有雌激素激动作用,可增加骨密度,但对人体副作用较少。为了研究SERM治疗是否可以预防双足C57Bl6小鼠模型中的脊柱侧凸进展以及与此效应相关的机制。
将80只C57BL6小鼠制成双足状态,并分为他莫昔芬(TMX)组、雷洛昔芬(RLX)组和对照组。TMX组和RLX组口服TMX和RLX,持续40周。进行前后位X线成像和组织形态计量学分析(在第20周和第40周)。
在第20周时,TMX组和RLX组显示出更高的发生率(p = 0.033,p = 0.029)和更大的曲线幅度(p = 0.018)。在第40周时,各组之间的曲线发生率相似,但TMX组和RLX组的曲线幅度较小(p = 0.001)。组织形态计量学显示,接受治疗的动物具有更高的小梁密度(p = 0.04)、更低的椎间盘总体积(p = 0.038)和生长板体积(p = 0.005)以及更小的椎体(p = 0.016)。
TMX或RLX治疗并未降低脊柱侧凸的发生率,但在40周时降低了曲线幅度。与曲线幅度降低相关的潜在机制可能是生长板的早期成熟,从而可能减缓脊柱的生长速度并增加骨密度。在褪黑素缺乏的双足小鼠中,RLX在预防脊柱侧凸曲线进展方面与TMX同样有效。