SGLT2 Inhibitors Increase Bone Strength by Increasing Procollagen Type 1 Amino-Terminal Propeptide in Patients with Type 2 Diabetes

With regard to osteoporosis in diabetic patients due to SGLT2 inhibitors (SGLT2is), there is no consensus on its onset as yet. At the meeting of the European Association for the Study of Diabetes in 2015, we reported improvement of bone strength after 6-month treatment with three SGLT2is as revealed by quantitative ultrasound analysis of 115 Japanese type 2 diabetic patients. In this study, we investigated the influence of SGLT2is on the bone strength, density and quality in Japanese patients with type 2 diabetes through both quantitative ultrasound analysis and D dual-energy X-ray absorptiometry (DEXA) before and after 6-month of SGLT2i treatment. The study was conducted in 19 Japanese patients with type 2 diabetes mellitus. Treatment with luseogliflozin 2.5 mg qd or dapagliflozin 5 mg qd for 6 months resulted in significant elevation of the ultrasound-measured bone density (ratio to young adults) of the heel from 88 ± 16% to 91 ± 15% (P<0.05). On the other hand, the lumbar spine bone density and femoral bone density measured by DEXA showed no significant difference before and after the treatment. Since the bone density measured by ultrasound is regarded to be equal to the bone quality + bone density, these results suggest that the bone density, reported to account for 70% of the bone strength, was not altered by the treatment with SGLT2is. In other words, the improvement of the bone strength revealed by ultrasound analysis appears to reflect improved bone quality rather than improved bone density. The serum level of TRACP-5b (a marker of bone destruction) did not differ significantly between before and after treatment, while the serum level of total procollagen type 1 amino-terminal propeptide (P1NP) increased significantly after the treatment (from 35.2 ± 10.3 μg/L to 39.0 ± 12.8 μg/L, P<0.05). The improvement of the bone quality and elevation of bone strength following treatment with SGLT2i appears to be correlated with elevation of the serum P1NP level.