Fig 2. TNF-Tg females exhibit accelerated bone loss with temporal transition from phalange to tarsal erosions.

Patterns of bone loss in particular hindpaw compartments (tarsals, red; metatarsals, blue; proximal phalanges, yellow; distal phalanges, white; and sesamoids, green) were analyzed for temporal and genotype effects. Representative images of hindpaws at 5-months of age are shown for wild-type males (starting sample size, n = 6 hindpaws), wild-type females (n = 8 hindpaws), TNF-Tg males (n = 8 hindpaws), and TNF-Tg females (n = 14 hindpaws) with the compartments labeled by colored stars (A-D). Although both TNF-Tg males and females exhibited consistent bone loss across time (E, *p<0.05, between timepoints), TNF-Tg females showed unique time-dependent erosions by particular compartment. For TNF-Tg females, there was a dramatic decrease in the bone volume of the tarsals between 4-5-months of age (F) that was preceded by early erosions starting at 2-months of age in the bones associated with the phalanges that was not sustained past 4-months (G-J). On the other hand, males showed relatively slow progression of erosions with limited statistical change for particular compartments at monthly intervals, except for the metatarsals (F-J). Also note the “U”-shaped progression of bone volumes in the TNF-Tg male sesamoids, likely representing bone remodeling and fusion following an initial period of erosions (J). Compared to wild-type mice, both TNF-Tg male and female mice showed significantly reduced bone volumes in all compartments starting at 3-months and 2-months of age, respectively (#p<0.05). Statistics: 2-way ANOVA (males) and mixed-effects analysis (females) with Tukey’s multiple comparisons (E-J).