Background:​ 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.

Method:​ 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.

Results:​ 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.

Conclusion:​ 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.