Lipid Dysregulation and Bone Fragility: Emerging Mechanisms in Osteoporosis Development

Shaban, Salma Mohamed; Gad El Rab, Mai Hassan; Mahrous, Sohair Maher; Abdel Rahman, Lamiaa Ahmed  Abdel Rahim; Fahmy, Mai Mahmoud

doi:10.21608/smj.2025.382583.1565

Lipid Dysregulation and Bone Fragility: Emerging Mechanisms in Osteoporosis Development

Document Type : Review Article

Authors

¹ Rheumatology and Rehabilitation, Faculty of medicine , sohag university

² Rheumatology

³ Rheumatology department faculty of medicine sohag university hospitals

⁴ Community medicine, faculty of medicine, Sohag university, Sohag, Egypt

⁵ rheumatology

10.21608/smj.2025.382583.1565

Abstract

Osteoporosis is a common and serious metabolic bone disorder that significantly impacts millions of individuals worldwide and places a growing burden on healthcare systems. It is primarily characterized by a progressive decline in bone mineral density, which increases the risk of fragility fractures and leads to a substantial reduction in quality of life. Traditional treatment approaches focus mainly on stimulating bone formation and preventing bone loss. However, a deeper understanding of the cellular and molecular mechanisms underlying osteoporosis is essential for the development of more effective therapies. Osteoblasts, the cells responsible for bone formation, originate from bone marrow mesenchymal stem cells (BM-MSCs), and their differentiation competes directly with adipocyte formation. This balance between osteogenesis and adipogenesis is regulated by several signaling pathways, most notably the Wnt/β-catenin pathway and the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. Recent research highlights the crucial role of lipid metabolism in the progression of osteoporosis. Lipids influence bone remodeling by modulating immune cell function, especially macrophages, which secrete pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α. These cytokines enhance osteoclastogenesis, shifting the bone remodeling process toward resorption. Furthermore, oxidative stress associated with obesity reduces antioxidant enzyme activity and impairs osteoblast function, worsening bone loss. This review emphasizes the interconnected roles of lipid metabolism, chronic inflammation, and oxidative stress in osteoporosis and suggests that managing these factors may offer promising strategies for improving bone health and developing more targeted treatments for osteoporosis.

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