Investigating the Association between Aquaporin-4 and Osteoporosis in Patients with Neuromyelitis Optica Spectrum Disorders

Background and Aim: Neuromyelitis Optica Spectrum Disorders (NMOSD) is an uncommon disorder of the central nervous system mainly affecting the optic nerves and spinal cord. NMOSD is associated with IgG antibody binding to aquaporin-4 (AQP4) that triggers astrocyte and axon loss. Aquaporin 4 is also expressed skeletally and affects bioenergetic regulation pathways and calcium (Ca²⁺) translocations. The aim of this study was the association between AQP4 and bone loss in NMOSD patients. Material and Methods: In this study, 32 NMOSD patients were enrolled as the case group, and 37 age-matched individuals without a history of neurological disorders or other acute or chronic conditions served as the control group. Patients with NMOSD were diagnosed based on the criteria established by Wingerchuk et al. Dual x-ray absorptiometry (DEXA) was used to assess bone mineral density (BMD) at three bone sites: the total hip, femoral neck, and spinal lumbar vertebrae (L1-L4). Bone status was defined based on the Z-score in these regions, with a Z-score less than -2 classified as severe bone loss. Results: Among patients with NMOSD, 15.6% exhibited severe bone densitometry loss in at least one area (total hip, femoral neck, or spine), compared to 5.4% in the control group (P=0.01). Bone densitometry results showed that the Z-score in the femoral neck and hip regions was significantly lower in individuals with NMOSD compared to the control group (P<0.05). In NMOSD patients, the Z-score in the femoral neck and hip regions was considerably lower in aquaporin-4 positive patients compared to the control group (P<0.05). In the regression model, after adjusting for age, sex, body mass index, and history of vitamin D supplementation, patients with aquaporin-4 had lower bone mass (P=0.02). Conclusion: The study results indicate that aquaporin-4 may play a mediating role in the bone status of patients with NMOSD.