osteoprotegerin and Scoliosis

Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS), and ghrelin has been shown to have a positive effect on bone metabolism. However, the circulating level of ghrelin is increased in AIS osteopenia, and the relationship between ghrelin and low bone mass in AIS osteopenia remains unclear.. A total of 563 AIS and 281 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Plasma ghrelin levels were determined by enzyme-linked immunosorbent assay (ELISA) in both AIS and control groups. An improved multiplex ligation detection reaction was performed to analyze single-nucleotide polymorphisms (SNPs). Facet joints were collected and subjected to immunohistochemistry; osteogenic gene and protein expression was also measured. Furthermore, primary cells were extracted from facet joints and bone marrow to observe the response to ghrelin stimulation.. The body mass index was lower and circulating ghrelin was markedly higher in the AIS osteopenia group than in the control group. No significant difference was observed in four ghrelin level-related SNPs between the AIS osteopenia and control groups. RNA and protein analyses revealed higher RANKL/OPG and lower runx2 levels in AIS cancellous bone. Compared with normal primary osteoblasts and BMSCs, AIS osteopenia primary cells were insensitive to the same ghrelin concentration gradient and showed lower osteogenic ability, increases in OPG and decreases in RANKL.. Our results indicate that high circulating ghrelin levels may not result from gene variations in AIS osteopenia. Dysregulation of the ghrelin/RANKL/OPG pathway may lead to decreased osteogenic ability of osteoblasts and BMSCs, which may be related to lower bone mass in AIS osteopenia.

Topics: Adolescent; Bone Density; Bone Diseases, Metabolic; Ghrelin; Humans; Kyphosis; Osteoprotegerin; RANK Ligand; Scoliosis

Osteopenia have been well documented in adolescent idiopathic scoliosis (AIS). Adiponectin has been shown to be inversely proportional to body mass index and to affect bone metabolism. However, the circulating levels of adiponectin and the relationship between adiponectin and low bone mass in AIS remain unclear.. A total of 563 AIS and 281 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay (ELISA) in the AIS and control groups. An improved multiplex ligation detection reaction was performed to study on single nucleotide polymorphism. Facet joints were collected and used to measure the microstructure, the expression of RANKL, OPG, osteoblast-related genes, inflammatory factors, adiponectin and its receptors by qPCR, western blotting and immunohistochemistry. Furthermore, primary cells were extracted from facet joints to observe the reaction after adiponectin stimulation.. Our results indicated that high circulating adiponectin levels may result from gene variations in AIS osteopenia. Adiponectin has a negative effect on bone metabolism, and this negative effect might be mediated by the ADR1-RANKL/OPG and ADR1-IL6 pathways.

Topics: Adiponectin; Adolescent; Bone and Bones; Bone Diseases, Metabolic; Case-Control Studies; Female; Humans; Interleukin-6; Male; Organ Size; Osteoblasts; Osteoclasts; Osteoprotegerin; Polymorphism, Single Nucleotide; RANK Ligand; Receptors, Adiponectin; Scoliosis; Signal Transduction; Spine; X-Ray Microtomography; Zygapophyseal Joint

Adolescent idiopathic scoliosis (AIS) is a complex three dimensional spinal deformity which occurs mostly in prepubertal and pubertal girls. Although bracing and surgery have been the mainstays of treatment for AIS, because of the complications and poor compliance, many patients with this disorder continue to experience significant residual symptoms. The etiology and pathogenesis of AIS is unclear, but recent studies show the association between osteopenia and AIS and imply that osteopenia play a causative role in the development of AIS. Anti-osteoporosis treatment can improve bone strength, prevent osteoporosis and rebalance the OPG-RANK-RANKL system, which may help to prevent curve progression in AIS. This report proposes that anti-osteoporosis treatment may be an effective treatment for AIS.

Topics: Adolescent; Antibodies, Monoclonal, Humanized; Bone Diseases, Metabolic; Denosumab; Female; Humans; Models, Biological; Osteoprotegerin; Piperidines; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; 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.

Topics: Adolescent; Base Sequence; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Child; DNA Mutational Analysis; Female; Femur Neck; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Lumbar Vertebrae; Osteoporosis; Osteoprotegerin; Polymorphism, Genetic; Radiography; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Scoliosis