Is decreased bone mineral density associated with development of scoliosis? A bipedal osteopenic rat model

<p>Abstract</p> <p>Background</p> <p>An association between adolescent idiopathic scoliosis and osteopenia has been proposed to exist. It is still not clear whether there is such an association and if so, whether osteopenia is a causative factor or a consequence. Our previous pilot studies have suggested the presence of osteopenia in scoliotic animals. The aim of this study was to investigate the development of scoliosis in an unpinealectomized bipedal osteopenic rat model, implementing osteoporosis as a causative factor.</p> <p>Methods</p> <p>Fifty Sprague-Dawley rats were rendered bipedal at the 3^rdpostnatal week and separated into control (25 rats) and heparin (25 rats receiving 1 IU/gr body weight/day) groups. DEXA scans after 4 weeks of heparin administration showed low bone mass in the heparin group. Anteroposterior and lateral x-rays of the surviving 42 animals (19 in heparin and 23 in control groups) were taken under anesthesia at the 40^thweek to evaluate for spinal deformity. Additional histomorphometric analysis was done on spine specimens to confirm the low bone mass in heparin receiving animals. Results of the DEXA scans, histomorphometric analysis and radiological data were compared between the groups.</p> <p>Results</p> <p>Bone mineral densities of rats in the heparin group were significantly lower than the control group as evidenced by both the DEXA scans and histomorphometric analyses. However, the incidence of scoliosis (82% in heparin and 65% in control; p > 0.05) as well as the curve magnitudes (12.1 ± 3.8 in heparin versus 10.1 ± 4.3 degrees in control; p > 0.05) were not significantly different. Osteopenic rats were significantly less kyphotic compared to control specimens (p = 0.001).</p> <p>Conclusions</p> <p>This study has revealed two important findings. One is that bipedality (in the absence of pinealectomy) by itself may be a cause of scoliosis in this animal model. Further studies on animal models need to consider bipedality as an independent factor. Secondly, relative hypokyphosis in osteopenic animals may have important implications. The absence of sagittal plane analyses in previous studies makes comparison impossible, but nonetheless these findings suggest that osteopenia may be important in the development of 3D deformity in adolescent idiopathic scoliosis.</p

Association between osteoprotegerin gene polymorphism and bone mineral density in patients with adolescent idiopathic scoliosis

Generalized low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic scoliosis (AIS) patients. Recently, many studies have shown that gene polymorphisms are related to osteoporosis. However, no studies have linked the association between gene polymorphisms and bone mass of AIS. Therefore, this study examined the association between the bone mass and RANKL, RANK, and OPG gene polymorphisms in 198 girls diagnosed with AIS. OPG 163 A → G, 209 G → A, 245 T → G, and 1181 G → C polymorphisms; RANK 421 C → T and 575 C → T polymorphisms; and RANKL rs12721445 and rs2277438 polymorphisms, as well as the bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed. The 163 A → G, 209 G → A, and 245 T → G polymorphisms in the OPG gene were in complete linkage. No RANK 421 C → T and 575 C → T polymorphisms or RANKL rs12711445 polymorphism were observed. There was a significant association between the OPG gene 1181 G → C polymorphism and LSBMD. LSBMD in AIS with the CC genotype was found to be significantly higher than in AIS with the GC (P < 0.05) or GG (P < 0.01) genotype. However, there was no significant association between LSBMD or FNBMD and the OPG gene 245 T → G polymorphism or the RANKL rs2277438 polymorphism. These results suggest that the OPG gene 1181 G → C polymorphism is associated with LSBMD in girls with AIS

Polymorphism in vitamin D receptor is associated with bone mineral density in patients with adolescent idiopathic scoliosis

Low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic scoliosis (AIS) patients. Furthermore, several recent studies have shown that gene polymorphisms are related to osteoporosis. However, no study has yet linked polymorphisms in the vitamin D receptor (VDR) gene and bone mass in AIS. Accordingly, the authors examined the association between bone mass and VDR gene polymorphisms in 198 girls diagnosed with AIS. The VDR BsmI (rs1544410), FokI (rs2228670) and Cdx2 (rs11568820) polymorphisms and bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed and compared to their levels in healthy controls. Mean LSBMD and FNBMD in AIS patients were lower than in age- and sex-matched healthy controls (P = 0.0022 and P = 0.0013, respectively). A comparison of genotype frequencies in AIS patients and controls revealed a significant difference for the BsmI polymorphism only (P = 0.0054). Furthermore, a significant association was found between the VDR BsmI polymorphism and LSBMD. In particular, LSBMD in AIS patients with the AA genotype was found to be significantly lower than in patients with the GA (P < 0.05) or GG (P < 0.01) genotypes. However, no significant association was found between LSBMD or FNBMD and the VDR FokI or Cdx2 polymorphisms. These results suggest that the VDR BsmI polymorphism is associated with LSBMD in girls with AIS