# The impact of dyslipidemia on skeletal health - from an immunoregulatory perspective

## TL;DR

This review explores how abnormal lipid levels affect bone health by altering immune responses, leading to conditions like osteoporosis.

## Contribution

The paper provides a comprehensive overview of the lipid–immune–bone axis and its role in metabolic bone diseases.

## Key findings

- High lipid levels shift macrophages to a pro-inflammatory state, promoting bone resorption.
- Hyperlipidemia disrupts T-cell balance, increasing osteoclast activity through Th17/Treg imbalance.
- B cells contribute to bone damage by switching from protective to destructive cytokine production.

## Abstract

Dyslipidemia and obesity are key risk factors for cardiometabolic diseases and are also linked to osteoporosis and other bone disorders. Evidence shows lipid metabolism influences bone homeostasis largely through immune regulation. This review first explains how abnormal lipid metabolism disrupts adipogenic and osteogenic differentiation in bone marrow mesenchymal stem cells and alters adipokines like leptin and adiponectin, upsetting bone formation and resorption and leading to bone loss. It then examines the lipid–immune–bone axis. In innate immunity, high lipid levels shift macrophages from M2 to pro-inflammatory M1, increase bone-resorbing cytokines such as TNF-α and IL-1β, and trigger neutrophil senescence and lipid peroxidation with excess reactive oxygen species, all of which promote osteoclast formation and suppress bone growth. In adaptive immunity, hyperlipidemia changes T-cell metabolism, weakens Treg function, and drives Th17 differentiation; this Th17/Treg imbalance boosts osteoclasts via RANKL, IL-17, and related pathways. Meanwhile, in inflammation, B cells switch from producing OPG to releasing RANKL and G-CSF, while Breg-derived IL-10, IL-35, and TGF-β1 protect bone. The review also highlights how M1 macrophages and Th17 cells work together to worsen bone damage. Understanding these immune mechanisms could lead to new treatments for metabolic bone diseases. Despite these advances, the translation of these preclinical findings into clinical practice remains a challenge that warrants further investigation.