Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products

Area of Science:

• Space medicine
• Bone biology
• Pharmacology

Background:

• Microgravity causes bone loss in astronauts, with unclear mechanisms.
• Advanced glycation end products (AGEs) are implicated in microgravity-induced osteoporosis.
• Investigating interventions to prevent spaceflight-related bone loss is crucial.

Purpose of the Study:

• To investigate if blocking AGEs formation with irbesartan can improve microgravity-induced bone loss.
• To assess the impact of irbesartan on AGEs accumulation and bone quality in a simulated microgravity model.
• To explore the correlation between AGEs, reactive oxygen species (ROS), and bone alterations.

Main Methods:

• Utilized a tail-suspended (TS) rat model to simulate microgravity.
• Administered irbesartan to TS rats and assessed AGEs (pentosidine, NE-xLR, fAGEs) and ROS (8-OHdG) levels in bone.
• Evaluated bone microstructure, mechanical properties, dynamic bone histomorphometry, and cellular activity (Osterix, TRAP).

Main Results:

• Tail-suspension significantly increased AGEs and showed an upward trend in 8-OHdG in rat hindlimbs.
• Bone quality and formation were inhibited in TS rats, correlating with elevated AGEs.
• Irbesartan treatment significantly inhibited AGEs and 8-OHdG, improving bone quality and partially altering bone remodeling.

Conclusions:

• Elevated AGEs contribute to disuse bone loss under simulated microgravity.
• Irbesartan may inhibit AGEs production by reducing ROS, thereby improving bone quality.
• AGEs primarily affect trabecular bone remodeling, suggesting milieu-dependent effects under microgravity.