Work

Gender‐related differences in spontaneous osteoclastogenesis in knee osteoarthritis: A potential peripheral biomarker for early disease progression

Year: 2025

Type: article

Abstract: Purpose Osteoclastogenesis, the formation of bone‐resorbing osteoclasts (OCs) from peripheral blood mononuclear cells (PBMCs), is increasingly recognised as a process involved in the pathophysiology of osteoarthritis (OA). This study investigated the phenomenon of spontaneous osteoclastogenesis (OC formation without exogenous stimuli) as a potential peripheral biomarker in male and female patients with knee OA. Methods PBMCs were isolated from 40 patients with knee OA (20 males, 20 females; Kellgren–Lawrence [KL] Grades I–II) and cultured for 21 days without osteoclastogenic factors. OC viability (Alamar Blue assay), percentage of mature OCs (tartrate‐resistant acid phosphatase [TRAP] histochemical staining) and secretion of Cathepsin K (CTSK) and matrix Metalloproteinases (MMPs) 7 and 9 (enzyme‐linked immunosorbent assay [ELISA] tests) were assessed. Results Demographic and clinical characteristics are comparable between male and female patients. OC viability was also similar between groups ( p = 0.494). However, males exhibited a significantly higher percentage of mature OCs compared to females ( p < 0.001). ELISA analysis revealed significantly higher levels of MMP7 and MMP9 in males ( p < 0.001 for both), while CTSK levels did not differ significantly between groups ( p = 0.136). Conclusions This study provides the first evidence of spontaneous osteoclastogenesis in OA patients, even at early stages, and highlights significant sex‐related differences in OC maturation and protein secretion. These findings suggest that spontaneous osteoclastogenesis may reflect systemic dysregulation of bone resorption and could serve as a potential biomarker for OA progression. Larger, controlled studies are needed to validate its diagnostic and prognostic value. Level of Evidence Level I.

Source: Journal of Experimental Orthopaedics