Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model

Abstract

Purpose 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. Methods 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. Results 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). Conclusions 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.

Estrogen promotes the onset and development of idiopathic scoliosis via disproportionate endochondral ossification of the anterior and posterior column in a bipedal rat model

“…In our study, the Triptorelin treatment reduced the incidence of scoliosis caused by estrogen. Our results on scoliosis rates in bipedal rat models differ from the results obtained by Demirkiran and colleagues 27 . The authors found that treatment with Tamoxifen (TMX) or Raloxifene (RLX) did not reduce the incidence of scoliosis, but TMX or RLX decreased the rate of progression of the deformity.…”

Cerebrospinal fluid velocity changes of idiopathic scoliosis: a preliminary study on 3-T PC-MRI and 3D-SPACE-VFAM data

“…IS is the most common (84-89%) form of scoliosis and is frequently seen in young people and called adolescent IS [9]. The etiology or mechanism of scoliosis is not fully understood [2].…”

“…The etiology or mechanism of scoliosis is not fully understood [2]. The most common etiopathogenesis of IS includes maturation disorders of the central and peripheral nervous system, connective tissue disorders in elastic and collagen fibers, muscle and bone diseases, platelet disorders, melatonin, hormone imbalances, genetic abnormalities, and leptin deficiency (essential in central nervous system development) [9][10][11]. Also, single nucleotide polymorphisms or any mutation related to ciliary functions and growth-regulating proteins may be related to IS development and progression [11][12][13].…”

Etiopathogenesis of adolescent idiopathic scoliosis: Expression of melatonin receptors 1A/1B, calmodulin and estrogen receptor 2 in deep paravertebral muscles revisited

“…Among other molecules involved in the melatonin signaling pathway, the role of estrogen receptors and CALM1 have attracted the attention of several investigators. Previous experimental studies have demonstrated that although selective estrogen receptor modulators, and CALM1 antagonists, do not prevent the occurrence of scoliotic deformities, they can decrease the rate of progression of the deformity in experimental animals (45)(46)(47). Conversely, replication studies and a meta-analysis did not confirm the previously suggested association between estrogen receptor gene polymorphisms and AIS predisposition or curve severity in humans (48)(49)(50)(51).…”