Canagliflozin versus soy isoflavone for bone metabolism in model rats with type 1 diabetes mellitus

Objective To compare the effect of canagliflozin (CGLZ) and soy isoflavone (SIF) on bone metabolism in model rats with type 1 diabetes mellitus.

Methods Forty male SD rats were randomly divided into control group, model group, SIF group, low-dose CGLZ group and high-dose CGLZ group, with 8 rats in each group. Model group and treatment groups were intraperitoneally injected with streptozotocin for modeling. The rats in treatment groups were gavaged daily for 12 weeks. During and after treatment, the body mass, food intake, water consumption, fasting blood glucose (FPG), serum albumin (ALB), serum calcium (SCa), serum phosphorus (SP), serum creatinine (Scr), serum 25 hydroxyvitamin D (25-OH-D₃), urine protein (Pro), urine creatinine (Ucr), urine protein to urine creatinine ratio (UPCR) and bone metabolism related indicatorstotal bone mineral density (TBMD), regional bone mineral density (RBMD), total body salt content (TBSC), total body fat mass (TBFM) and total body muscle mass (TBMM)of rats in each group were detected. Detection sites of RBMD included head, upper limb, thigh, trunk, rib, pelvis and spine.

Results After 12 weeks of successful modeling, the water intake and food consumption of rats in model group, SIF group, low-dose CGLZ group and high-dose CGLZ group all increased, while the body mass decreased; after medication, the body mass of rats in low-dose CGLZ group and high-dose CGLZ group increased, and increased range of body mass in high-dose CGLZ group was significantly greater than that in the SIF group. The FPG level of rats after 4 weeks of treatment in low-dose CGLZ group and high-dose CGLZ group as well as after 8 and 12 weeks of treatment in the SIF group, low-dose CGLZ group and high-dose CGLZ group decreased, and efficacy ranking from high to low was high-dose CGLZ group, low-dose CGLZ group and SIF group. After 12 weeks of treatment, Pro, Ucr and UPCR of rats in each treatment group decreased significantly (P < 0.01); in the SIF group, low-dose CGLZ group and high-dose CGLZ group, serum ALB level increased significantly while Scr level decreased significantly(P < 0.01); the level of 25-OH-D₃ in high-dose CGLZ group decreased significantly (P < 0.01). After treatment of 12 weeks, TBSC in high-dose CGLZ group increased, but TBMD, TBSC, TBFM and TBMM did not increase in SIF group and low-dose CGLZ group; the increase of bone mineral density was observed in the thigh of high-dose CGLZ group, the trunk, ribs and spine of low-dose CGLZ group and high-dose CGLZ group, and the pelvis of SIF group and high-dose CGLZ group.

Conclusion Both CGLZ and SIF can reduce hyperglycemia induced by streptozotocin in model rats with type 1 diabetes mellitus, and the effect of the former is better. In terms of improving the total body bone salts, total body bone mineral density and bone mineral density at all sites, the effect of high-dose CGLZ is better than that of low-dose CGLZ, while SIF can only improve the bone mineral density of pelvis to a certain extent.