(A) Male mice, 10 weeks old, received vehicle (Control) or 2 doses of streptozotocin (STZ) to induce type 1 diabetes, and blood glucose was measured 14 days later. Twenty-eight days after the start of STZ, control and diabetic mice (glucose > 290 mg/dL) received a 0.8-mm burr hole on the anterior surface of the right tibia, as described in Figure 2. On postsurgical days (PSD) 1–9, mice were given daily intraperitoneal injections of either vehicle or cinaciguat (10 μg/kg/d), and they were euthanized on PSD 10. (B) μCT images of mineralized bone formed in the drill hole defect were reconstructed in 3D as described in Supplemental Figure 3. (C) Bone volume fraction (BV/TV), bone mineral density (BMD), trabecular number (Tb.N), and trabecular spacing (Tb.Sp) were determined in the “volume of interest,” centered in the cortical defect, as described in Figure 2B (n = 7 mice in each of the control groups, and n = 8 mice in each of the diabetic groups). (D and E) Collagen stained by aniline blue was measured on trichrome-stained sections, as described in Figure 2C, in the 0.1-mm² “region of interest” in the defect of the injured tibiae (n = 5–6 mice per group; scale bars: 50 μm). (F) Osteoblasts attached to newly formed BSs in the region of interest were counted on trichrome-stained sections (n = 5–6 mice per group). (G) Vegfa, Bmp2, and Bmp4 mRNAs were quantified by qRT-PCR in tibiae of control and diabetic mice treated with vehicle or cinaciguat (Cin); mRNA amounts were normalized to 18S rRNA, and the mean mRNA level found in tibiae of vehicle-treated control mice was assigned a value of 1 (n = 6–7 mice per group). The graphs show means ± SEM; *P < 0.05, **P < 0.01, and ***P < 0.001 for the indicated pairwise comparisons by 2-way ANOVA. ^#P < 0.05, ^##P < 0.01, and ^###P < 0.001 for the comparison with untreated control mice.