Jiang Li,1,2,* Min Liu,2,* Jian Qin,1,2 Yuxiao An,2 Xiuzhu Zheng,2 Noor Shafini Mohamad,3 Izzad Ramli4 

1Centre for Medical Imaging, Faculty of Health Sciences, Universiti Teknologi MARA, Selangor, Puncak Alam Campus, Bandar Puncak Alam, Selangor, Malaysia; 2Medical Imaging Department, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China; 3Medical Imaging Department, Faculty of Health and Life Sciences, St Luke’s Campus, Exeter, UK; 4College of Computing, Informatics and Mathematics, Universiti Teknologi MARA, Shah Alam, Selangor Darul Ehsan, Malaysia

*These authors contributed equally to this work

Correspondence: Noor Shafini Mohamad, Medical Imaging Department, Faculty of Health and Life Sciences, St Luke’s Campus, Exeter, UK, Email N.Mohamad@exeter.ac.uk Izzad Ramli, College of Computing, Informatics and Mathematics, Universiti Teknologi MARA, Email izzadramli@uitm.edu.my

Background: Diabetic osteoporosis (DOP) can cause abnormal brain neural activity, but its mechanism is still unclear. This study aims to further explore the abnormal functional connectivity between different brain regions based on the team’s previous research.
Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were obtained from 14 participants diagnosed with type 2 diabetes mellitus (T2DM) and osteoporosis. For comparison, data from 13 T2DM patients without osteoporosis were analyzed. The seed regions for functional connectivity (FC) analysis were chosen according to brain areas previously reported to exhibit abnormal regional homogeneity (ReHo).
Results: DOP patients exhibited significantly decreased BMD, T-scores, MoCA scores, and osteocalcin (OC) levels compared to controls (p< 0.05). FC analysis revealed: 1) Reduced connectivity between the left middle temporal gyrus (increased ReHo) and middle occipital gyrus; 2) Enhanced connectivity between the right angular gyrus (increased ReHo) and left Rolandic operculum; 3) Weakened the left precuneus (increased ReHo) and right superior/left middle frontal gyri. These alterations correlated with deficits in visual processing, working memory, and executive function.
Conclusion: Distinct FC reorganization in DOP patients reflects synergistic effects of metabolic and skeletal pathologies on neural networks, potentially mediating cognitive decline through visual pathway disruption and prefrontal-default mode network decoupling. The findings highlight neuroimaging biomarkers for metabolic bone disease-related cognitive disorders.

Keywords: diabetic osteoporosis, functional connectivity, regional homogeneity, bone mineral density