ObjectiveTo evaluate gender differences in the association between metacarpal cortical thickness - a surrogate for bone density - and severity of radiographic hand osteoarthritis (HOA) in a longitudinal observational study. MethodHand radiographs of 3,575 participants (2039 F/1536 M) from the Osteoarthritis Initiative were assessed at baseline and 48 months. A reader used a semi-automated software tool to calculate Tcort, a measurement of the cortical thickness, for metacarpals 2-4. Average Tcort at baseline and change in Tcort from baseline to 48 months was determined and stratified by gender and age for 7 5-year age groups. Spearman’s rank correlation coefficients were calculated for the association of baseline Tcort and 2 measures of baseline HOA severity: the sum of Kellgren and Lawrence (KL) grade and total number of joints with radiographic HOA. Longitudinally, logistic regression was used to assess the relationship of Tcort loss to new finger joint radiographic HOA, increase in KL grades, and incident hand pain. ResultsMale Tcort was higher than females. Significant correlations between Tcort and radiographic severity were noted for women but not men, with stronger associations among women >60 years (rho=-0.25; 95% CI= -0.31- -0.19). Statistically significant associations were seen between Tcort change and radiographic osteoarthritis change among women but not men, with substantial gender differences for Tcort change, particularly ages 50 to 70 years (p<0.01; e.g.Tcort change ages 55 to <60: Males=-0.182(0.118), Females=-0.219(0.124). ConclusionWe found significant HOA-related gender differences in cortical thickness, suggesting the involvement of female bone loss during and after menopause.