Nicotinamide Riboside Restores Bone Health in Glucocorticoid-Induced Osteoporosis: Preclinical Findings

Synopsis

Glucocorticoid-induced osteoporosis (GIOP) is a major side effect of long-term steroid use, caused by damage to osteoblasts—the bone-forming cells. Recent studies show that ferroptosis, a type of cell death driven by iron and oxidative stress, plays a central role in this process. This study explored how mitochondrial dysfunction and SIRT3, a key NAD+-dependent enzyme, regulate ferroptosis in GIOP. In rat models treated with glucocorticoids, researchers observed osteoblast injury, increased ferroptosis markers, and reduced SIRT3 expression. Although an iron chelator (deferoxamine) reduced ferroptosis, it did not restore bone-forming activity, indicating that additional pathways were involved. Transcriptomic analysis revealed a strong link between SIRT3 and mitophagy (mitochondrial self-clearance). In cell experiments, glucocorticoids caused excessive mitophagy, mitochondrial damage, and SIRT3 suppression. Treatment with nicotinamide riboside (NR)—a vitamin B3–derived SIRT3 activator—restored mitochondrial health, reduced ferroptosis, and improved osteoblast function. These findings show that SIRT3 protects bone cells by preventing overactive mitophagy and oxidative stress, and that NR supplementation could serve as a potential therapy for glucocorticoid-induced bone loss.

Journal

International Journal of Surgery