Bone Abstracts

Objectives: Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine and its etiology remains unknown. Girls with AIS have taller stature, longer arm span, lower BMI, and generalized osteopenia. Leptin has been postulated as one of the etiologic factors of AIS because of its important physiological functions in neuro-osseous development affecting skeletal growth, bone metabolism, energy expenditure and body composition. Previous studies on the relationship between leptin and HR-pQCT derived bone quality parameters had found abnormal correlations in AIS girls, and suggested possible abnormalities in the leptin regulated bone metabolic pathways. This study aimed to investigate and compare the effect of leptin on the functional responses of osteoblasts in AIS and control subjects.

Methods: In vitro assays were performed on osteoblasts cultured from biopsies obtained intraoperatively from 12 AIS girls and six control subjects. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/ml). Cell proliferation was evaluated with MTT assay; differentiation with ALP activity assay and osteocalcin ELISA; and mineralization with von Kossa staining.

Results: Leptin stimulated control osteoblasts to proliferate in a dose dependent manner, while AIS osteoblasts showed no proliferative response to leptin. For differentiation, control group showed significant increasing trends in ALP activity and osteocalcin secretion to increasing leptin concentrations, while no responses were observed in the AIS osteoblasts (Fig. 1A). For mineralization, control osteoblasts showed increasing amount of calcium nodules to leptin concentrations, and again no response was observed in AIS (Fig. 1B).

Conclusion: The results indicated that the AIS osteoblasts had significantly lower functional response to leptin challenge when compared with controls. The observation might be related to dysfunction of the leptin signaling pathway and accounting for the low bone mass and deranged bone quality reported in AIS. Further studies would be warranted.

Disclosure: The authors declared no competing interests.

Figure 1A Effect of leptin on alkaline phosphatase (ALP) activity of osteoblasts from control and AIS patients after 14 days of leptin treatment. B. von Kossa staining of control and AIS osteoblasts at day 14, 21, 28, and 35. Formation of calcium nodules in control osteoblast increased as the days of treatment and leptin concentration increases, but AIS osteoblast showed no response to leptin treatment.