Figure 6. An FTI (ABT-100) ameliorates bone disease in Lmna^HG/+ mice.

(A) Radiographs of a 6-month-old vehicle-treated Lmna^HG/+ mouse and a littermate FTI-treated Lmna^HG/+ mouse. (B) Kyphotic index in FTI-treated and vehicle-treated Lmna^HG/+ and Lmna^+/+ mice. The degree of kyphosis in Lmna^HG/+ mice was greater (a smaller kyphotic index) than in Lmna^+/+ mice (P < 0.0001) and was significantly reduced (a larger kyphotic index) after FTI treatment (P = 0.02; n = 10 per group). (C) Reduced number of rib fractures in FTI-treated Lmna^HG/+ mice. After 24 weeks, surviving mice were euthanized, and the number of rib fractures was counted. The number of rib fractures in the FTI-treated Lmna^HG/+ mice was significantly lower than in vehicle-treated Lmna^HG/+ mice (P < 0.0001). (D) μCT scans illustrating reduced numbers of rib fractures in FTI-treated Lmna^HG/+ mice. Red arrowheads indicate rib fractures and surrounding callus. In the FTI-treated mouse, there was thinning of 1 rib along with a small amount of callus. No rib fractures were observed in Lmna^+/+ mice. (E and F) FTI treatment improved bone mineralization (E) and bone cortical thickness (F) in Lmna^HG/+ mice without affecting the bones of Lmna^+/+ mice. Error bars are too small to be seen in E. gHA/cm³, grams of hydroxyapatite per cubic centimeter.