Effects of teriparatide on bone in autochthonous transgenic model mice for diabetes mellitus (Akita mice)

Abstract

Objectives: The purpose of this study is to evaluate the effects of teriparatide (TPTD) on bone mineral density (BMD), bone strength, and bone quality in Akita mouse models of diabetes mellitus. Methods: Twelve-week-old female Akita mice and control mice (C57/BL/6NCrSlc) were divided into 4 groups: control mice treated with vehicle (n = 7) or TPTD (n = 6); and Akita mice treated with vehicle (n = 6) or TPTD (n = 7). TPTD or vehicle was administered subcutaneously 3 times a week for 8 weeks. Blood glucose, serum sclerostin, total tibial BMD, femoral shaft bone strength, and bone quality using Fourier-transform infrared spectroscopy imaging were evaluated. Results: No significant differences in serum sclerostin levels were evident among these groups after 8 weeks of treatment. TPTD significantly increased BMD in control mice (+12.7%, P = 0.02) and Akita mice (+29.2%, P = 0.001) compared with vehicle. Maximum load and stiffness were significantly higher in Akita mice treated with TPTD than in Akita mice treated with vehicle (+56.6%, P = 0.03 and + 90.5%, P = 0.02, respectively). On Fourier-transform infrared spectroscopy imaging, the mineral/matrix ratio was significantly lower in Akita mice treated with vehicle than in control mice (−12.2%, P = 0.02), and TPTD treatment significantly increased the mineral/matrix ratio (P = 0.003). Conclusions: TPTD thus improved BMD and bone strength in both control mice and Akita mice, with improvements in the mineral/matrix ratio among Akita mice. Keywords: Diabetes mellitus, Akita mouse, Teriparatide, Bone mineral density, Bone strength, Bone quality