Fine Line Between Repair & Ruin: How Inflammation Shapes Bone Remodelling?

Inflammation serves as both a stimulus for bone regeneration and a driver of deterioration. Although the process of bone remodelling is strictly regulated by osteoblasts, osteoclasts, osteocytes, and bone-lining cells, immunological signalling significantly affects how it is balanced. Acute inflammation is crucial for initiating bone repair because cytokines such as IL-1, IL-6, and TNF-α draw neutrophils and macrophages to the fracture site, clear debris, and encourage mesenchymal stem cell differentiation into osteoblasts. However, prolonged or dysregulated inflammation promotes bone loss by tilting the RANKL/OPG axis in favour of osteoclastogenesis, a characteristic of diseases such as inflammatory bowel disease, periodontitis, and rheumatoid arthritis. The new field of osteoimmunology shows how immune cells have two different effects: Th17 cells, hyperactivated neutrophils, and pro-inflammatory macrophages speed up bone resorption, while Tregs, osteomacs, and B cell-derived OPG encourage regeneration. This review emphasises how inflammation's temporal, cellular, and molecular context determines skeletal outcomes, highlighting the thin line separating repair from ruin. Comprehending this osteoimmune paradox offers therapeutic options, such as immune cell reprogramming, cytokine modulation, and RANKL inhibition, to promote bone regeneration while reducing inflammation-induced bone loss.