gms | German Medical Science

Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a major socio-economic impact. Higher incidence of bone fractures in children and adults with ASD, urge the investigation of alterations in the bone metabolism.

Methods: To assess the effect of autism on bone metabolism, knockout mouse models of Neuroligin 3 (NL3-/-, n=8) and Neuroligin 4 (NL4-/-, n=15) were compared with wild type (WT, n=12). After the establishment of autistic behaviour, whole body Dual X-ray Absortiometry (DXA) was carried out. After euthanasia, long bones were collected followed by radiological, biomechanical, and histological analysis of hind limbs.

Results and conclusion: Whole body DXA showed slightly higher Bone Mineral Density (BMD) in NL4-/- (Mean±SD: 0.077 ± 0.007) compared with WT (0.074 ± 0.0121). Fat% was significantly lower in NL4-/- compared with the WT (p=0.005). Movat Pentachrome stain of femora showed significantly lower non-mineralized matrix in NL3-/- when compared with NL4-/- (p = 0.011) and WT (p = 0.019). Higher trend of cartilaginous tissue area was seen in NL3-/- when compared with both WT and NL4-/-. Whereas, no difference in the calcified tissue area was seen between the groups. Although lower in both knockouts than WT, osteoclast activity assessment using TRAP enzymehistochemistry showed higher number of osteoclast in the NL3-/-group compared to the NL4-/- but not to the WT. Osteocalcin immunostaining showed increased positive area inNL3-/-group compared to the other two groups. Same pattern was also seen for number of M2 cells in bone marrow, where M1 cell number was higher in both knockouts compared to the WT.

ASD is a group of behavioural disorders clinically defined by significant function impairment. Neumeyer et al. 2015 reported the higher frequency of fractures with lower BMD among young adults with ASD. The offered treatment for ASD patients is risperidone and aripiprazole, both are steroid-based and were reported to increase fracture risk. The histological results show an imbalance in fat accumulation, bone density and cellular imbalance suggesting a regulatory role for bone cells in autism. Correlation between bone and behavioural diseases is shown in other animal models such as Tryptophan hydroxylase 2 knockout rats. Furthermore, neurological diseases with skeletal manifestation such as neurofibromatosis are managed through mesenchymal cell therapy. Such an approach in autism patient might prove beneficial for their overall health.