Endocrine Abstracts

Background and aims

Although bone fracture risk increases in DM, bone mineral density does not completely reflect bone fragility. It is important to explore other methods of osteoporotic fracture risk evaluation. Nowadays bone turnover markers (BTM) investigation is not widely used in clinical practice. On the other hand, the action of some glucose-lowering drugs on bone remodeling is not completely explored. The aim of this study was to investigate and to compare BTM in diabetic rats during treatment with sitagliptin (SITA), canagliflozin (CANA), and empagliflozin (EMPA).

Materials and methods

Type 2 DM was modelled in male Wistar rats by high-fat diet and streptozotocin+nicotinamide. 4 weeks after rats were divided into 4 groups: “DM” (n = 4), “SITA” (n = 4) (treatment with SITA 50 mg/kg 8 weeks) “CANA” (n = 4) (CANA 25 mg/kg for 8 weeks), “EMPA” (n = 4) (EMPA 2 mg/kg 8 weeks). Also, there was a control group “CRL” (n = 4) treated with vehicle. Blood glucose level (BGL) was studied every 3^rd day during the experiment. Blood samples for BTM (osteocalcin, OCL, osteoprotegerin, OPG, RANKL) evaluation were obtained prior to euthanasia.

Results

Treatment with both SITA and EMPA led to moderate increase in OCL level compared with DM (19.57[17.85;24.44], 16.0[15.72;17.0] and 10.69[8.87;11.03] ng/ml respectively) though OCL level did not achieve CRL value (49.1[47.98;54.57]). OCL in “CANA” (9.06[6.21;16.87]) and “EMPA” (16.0[15.72;17.0]) groups was significantly lower than in “SITA” (19.57[17.85;24.44]) and “DM” (19.57[17.85;24.44]) groups. All antihyperglycemic drugs caused decrease in OPG: (6.28[3.06;9.99], 1.26[1.04;1.88] and 1.85[1.19;1.9] pmol/l for SITA, EMPA, CANA, respectively) compared with “CRL” (12.53[11.1;13.7]) and “DM” (14.58[6.12;15.65]). Both SGLT-2 inhibitors led to more prominent decrease in OPG level than SITA (P <0.01). RANKL level in SITA (248.38[220.81;300.96] pmol/l) and EMPA (254.1[231.62;284.0] pmol/l) groups did not significantly differ from CRL one (247.81[205.36;289.67]). At the same time, the use of CANA led to significant increase in RANKL (342.86[280.0;355.29]) in comparison with other glucose-lowering agents. However, the OPG/RANKL ratio did not differ between the CRL (0.53[0.38;0.66]) and DM (0.53[0.19;0.58]) groups and was higher compared with treatment groups (0.24[0.01;0.45] for SITA, 0.005[0.003;0.007] for EMPA and 0.005[0.003;0.007] for CANA). The lowest OPG/RANKL ratio was in the EMPA and CANA groups, with no differences between them.

Conclusions

Both EMPA and CANA decrease osteogenesis and increase bone resorption, while effect of CANA might be more pronounced which manifests in higher RANKL level.