# Protective Effect of Methyl Sulfonyl Methane on the Progression of Age-Induced Bone Loss by Regulating Oxidative Stress-Mediated Bone Resorption

## TL;DR

Methyl sulfonyl methane (MSM) helps reduce age-related bone loss by fighting oxidative stress and improving bone health in aged mice.

## Contribution

This study demonstrates that MSM supplementation reverses age-induced bone loss through antioxidant mechanisms.

## Key findings

- MSM improved bone microarchitecture and osteocyte gene expression in aged mice.
- MSM reduced bone resorption markers and pro-inflammatory cytokines in serum and bone marrow.
- MSM enhanced antioxidant status via activation of the Nrf2 pathway and related genes.

## Abstract

Aging is associated with detrimental bone loss, often leading to fragility fractures, which may be driven by oxidative stress. In this study, the outcomes of comparing the differences among young, adult and aged C57BL/6J mice found that the trabecular bone volume was significantly lower in the aged mice compared to young mice, and the bone characteristics were significantly correlated with the oxidative status. To counteract the adverse effects of aging, methyl sulfonyl methane (MSM), a stable metabolite of dimethyl sulfoxide, was used to supplement the drinking water (400 mg/kg/day) of the aged mice (73 weeks old) for 8 weeks. The MSM supplementation improved the maximum load, bone microarchitecture, and mRNA levels of osteocyte-specific genes in the tibia. Furthermore, MSM reduced the serum level of the C-terminal telopeptide of type I collagen, a marker of bone resorption, and downregulated the mRNA levels of genes related to osteoclast proliferation and activity. MSM also decreased the levels of pro-inflammatory cytokines in both the serum and bone marrow. Importantly, the MSM-treated mice exhibited an enhanced antioxidant status, characterized by increased glutathione peroxidase (GPx) activity and glutathione concentration in plasma, erythrocytes and bone marrow. These improvements were linked to the activation of the nuclear factor E2 related factor 2 (Nrf2) pathway and its downstream antioxidant gene expression, including that of superoxide dismutase and GPx. These findings suggested that age-related bone loss is closely tied to oxidative stress, and MSM supplementation effectively reverses bone loss by mitigating oxidative stress-mediated bone resorption.