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

Abstract

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. 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. Demographic and clinical characteristics are comparable between male and female patients. OC viability was also similar between groups (<i>p</i> = 0.494). However, males exhibited a significantly higher percentage of mature OCs compared to females (<i>p</i> < 0.001). ELISA analysis revealed significantly higher levels of MMP7 and MMP9 in males (<i>p</i> < 0.001 for both), while CTSK levels did not differ significantly between groups (<i>p</i> = 0.136). 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 I.