Complex network model reveals the positive effect of melatonin on bone parameters in rats with induced...

Melatonin (MEL) has been investigated as a strategy to prevent bone loss related to oestrogen deficiency. However, its systemic impact on multiple bone properties is not completely established. This study evaluated the effects of chronic MEL administration on bone parameters commonly compromised by hypoestrogenism, using complex network analyses as an innovative approach to integrate bone outcomes.

A total of 40 female Wistar rats were allocated into four groups: control + vehicle (CG), ovariectomized + vehicle (OG), melatonin (MG), and ovariectomized + melatonin (MOG). OG and MOG underwent bilateral ovariectomy (OVX) at 15 weeks of age. One week later, animals received daily melatonin (MG and MOG, 10 mg.kg^-1) or vehicle (CG and OG) via orogastric gavage during the dark period for 12 weeks. At the end, bilateral femora were collected for metric, physical, mechanical, chemical, and micro-CT analyses. Two-way analysis of variance (ANOVA) was conducted and parameter interactions were explored with complex network analyses with PageRank and Betweenness centrality metrics.

Traditional analyses confirmed that OVX impaired bone health, while MEL treatment improved mechanical strength and preserved bone properties. Overall, treated animals exhibited values closer to CG than to OG and complex network analyses elucidated the physiological adjustments in response to interventions. Centrality metrics indicated that MEL modulated parameters to enhance the bone's load-bearing capacity, while biophysical aspects were more central in other groups and became key connectors in MG with Betweenness centrality.

Our results suggest that MEL administration positively influences bone mechanics under different stress conditions and prevents deterioration related to osteometabolic disorders caused by OVX. Complex network analyses highlighted biomechanical variables as central in groups treated with MEL, while biophysical variables acted as key connectors. These findings provide an integrative understanding of the physiological adaptations promoted by MEL to maintain bone strength, through reorganization of the functional importance of biomechanical and biophysical parameters under hypoestrogenism conditions over 12 weeks.