Abnormal trabecular bone health and FIX to support bone preservation following hemarthrosis in normal and in FIX^−/−mice. (A) Experimental animals include the same conditions as in Figure 4, that is, 2-week postinjury images from sham-treated WT, sham-treated FIX^−/−, and hemophilia B mice treated at 20 minutes after wounding with a single dose of 250 IU/kg IV rFIX (Benefix) FIX^−/− + rFIX or a single dose of 250 IU/kg IV glycoPEGylated rFIX (N9-GP) FIX^−/− + N9-GP. Images of the trabecular bone region of analysis of the proximal tibia demonstrate less bone in the representative image from the injured, placebo-treated hemophilia B mouse when compared with the WT placebo-treated mouse, as well as relatively less good preservation of bone density by single-dose rFIX in comparison with N9-GP. (B) Quantitative analysis of vBMD outcomes at 2 weeks following injury. Although large variations between mice were seen within each group, single-dose rFIX only partially preserved connectivity density of the trabecular struts, whereas the N9-GP or the 2 week replacement with rFIX preserved connectivity. (C) Trabecular bone microarchitecture changes following hemarthrosis include increase in trabecular separation in hemophilia mice compared with mice with intact hemostasis. Mean trabecular separation was preserved following hemarthrosis (not different from WT) by each of the replacement rFIX and N9-GP approaches. Normal trabecular separation was preserved by a single dose of N9-GP but required multiple dose rFIX therapy. Points that are significantly different from “WT” are indicated by “*.” Points that are significantly different from “NS” are indicated by “#.” Markers of significance are used as follows: *P < .05, **P < .01, ^#P < .05, ^##P < .01.