Fig 6. Specific bones exhibit differential responses to anti-TNF therapy in TNF-Tg mice.

As we have noted that 6-weeks of anti-TNF therapy is sufficient to recover talus bone volumes in TNF-Tg male mice with severe arthritis at 8-months of age [50], we evaluated the response of individual bones in the tarsal region to determine reliable biomarkers of treatment effectiveness. Representative micro-CT images of the tarsal region in wild-type, placebo (IgG1 isotype antibodies) treated TNF-Tg, and anti-TNF treated TNF-Tg mice are shown. Note the general increase in bone volumes with anti-TNF therapy, although with continued abnormal bone morphology relative to wild-type (A-C). Measurements of total tarsal bone volume indicated effective response to anti-TNF relative to placebo treatment by 3-weeks post-treatment (wpt), although bone volumes remained lower than wild-type at 6wpt (D). Direct comparison of the treatment response between placebo and anti-TNF therapy for the individual bones revealed a heterogenous response. Although all bones exhibited a significantly increased bone volumes in anti-TNF compared to placebo treated TNF-Tg mice by 6wpt (E-J), effects of treatment type over time exhibited differential response between bones, quantified by η² effect size between placebo and anti-TNF groups (K, dashed line = large effect, >0.138). Statistics: 2-way ANOVA with Tukey’s multiple comparisons (D-J); * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. Sample sizes: wild-type, n = 8; placebo, n = 12; anti-TNF, n = 10 hindpaws (D-J).