Fig. 7: Combination studies of Wnt mimetic antibodies with currently available therapeutics.
From: Development of selective bispecific Wnt mimetics for bone loss and repair
a 12-week-old C57BL6/J female mice were injected bi-weekly for 28 days with intraperitoneal administration of FB-L5 (10 mg/kg) antibody and compared to a negative control anti-β-gal (10 mg/kg) and positive control bi-weekly subcutaneous administration of 25 mg/kg anti-sclerostin antibody or a combination of anti-sclerostin antibody and FB-L5. A 2-week washout period then followed (day 42 assessment). Longitudinal DEXA measurements were collected and whole-body % BMD change quantified for days 0, 14, 28, and 42, normalized to baseline. At day 28, combination treatment induced statistically significant increases in BMD compared to individual treatments. At day 42, combination treatment maintained the bone accrual gained during the first 4 weeks of treatment and remained statistically significant compared to individual treatments. b 12-week-old C57BL6/J female mice were injected bi-weekly for 28 days with intraperitoneal administration of FB-L5 (10 mg/kg) antibody and compared to a negative control anti-β-gal (10 mg/kg). From day 28 through day 42, animals were treated with either vehicle or alendronate at 1 or 4 mg/kg. Longitudinal DEXA measurements were collected and whole-body % BMD quantified for days 0, 14, 28, and 42, normalized to baseline. a, b Graphs represent mean values ± SD, n = 8 mice/group. Statistical significance determined by two-way ANOVA (**p < 0.01, ****p < 0.0001), where the following letters define groups, a (a = anti-β-Gal, b = Anti-Sclerostin, c = FB-L5, d = FB-L5 + Anti-Sclerostin) and b (a = anti-β-Gal + Vehicle, b = FB-L5 + Vehicle, c = FB-L5 + Alendronate (1 mg/kg), d = FB-L5 + Alendronate (4 mg/kg)). a Day 14, a vs. b, p ≤ 0.0001, a vs. c, p ≤ 0.0001, a vs. d, p ≤ 0.0001, b vs. c, p ≤ 0.0001, b vs. d, p ≤ 0.0001. Day 28, a vs. b, p ≤ 0.0001, a vs. c, p ≤ 0.0001, a vs. d, p ≤ 0.0001, b vs. c, p ≤ 0.0001, b vs. d, p ≤ 0.0001, c vs. d, p ≤ 0.0001. Day 42, a vs. b, p ≤ 0.0001, a vs. c, p ≤ 0.0001, a vs. d, p ≤ 0.0001, b vs. c, p = 0.0031, b vs. d, p ≤ 0.0001, c vs. d, p ≤ 0.0001. b Day 14, a vs. b, p ≤ 0.0001, a vs. c, p ≤ 0.0001, a vs. d, p ≤ 0.0001. Day 28, a vs. b, p ≤ 0.0001, a vs. c, p ≤ 0.0001, a vs. d, p ≤ 0.0001. Day 42, a vs. b, p ≤ 0.0001, a vs. c, p ≤ 0.0001, a vs. d, p ≤ 0.0001, b vs. c, p = 0.0023, b vs. d, p ≤ 0.0001.
