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Dapagliflozin Attenuates Hyperglycemia Related Osteoporosis in ZDF Rats by Alleviating Hypercalciuria

Ji-Yu Wang1, Yan-Zhen Cheng1, Shuang-Li Yang1,2

  • 1Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Frontiers in Endocrinology
|November 30, 2019
PubMed

Insights

Dapagliflozin may not worsen osteoporosis in type 2 diabetes. This study found Dapagliflozin alleviated bone loss and improved bone quality in diabetic rats, suggesting it may prevent osteoporosis by reducing urinary calcium excretion.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Bone Biology

Background:

  • Sodium-dependent glucose transporters 2 inhibitors (SGLT2I) are used for type 2 diabetes mellitus (T2DM).
  • Concerns exist regarding potential skeletal adverse effects of SGLT2I, including fracture risk.
  • The specific impact of Dapagliflozin on osteoporosis in T2DM patients remains debated.

Purpose of the Study:

  • To investigate the effects of Dapagliflozin on bone metabolism and quality in a T2DM animal model.
  • To determine if Dapagliflozin exacerbates or alleviates osteoporosis in the context of T2DM.

Main Methods:

  • Male Zucker Diabetic Fatty (ZDF) rats, a model for diet-induced T2DM, were treated with Dapagliflozin (10 mg/kg/day).
  • Bone mineral density and microarchitecture of tibiae were assessed using micro-CT.
  • Femoral biomechanics were evaluated using a three-point bending test.
  • Serum bone biomarkers and metabolic parameters were analyzed via ELISA and other assays.

Main Results:

  • Diabetic ZDF rats exhibited osteoporosis symptoms, including elevated serum calcitonin, urinary calcium, and phosphate levels.
  • Dapagliflozin treatment alleviated these diabetic bone-related metabolic disturbances.
  • While cortical bone mineral density decreased, trabecular and mean bone mineral density in tibiae increased with Dapagliflozin.
  • Dapagliflozin administration improved femoral stiffness in diabetic rats.

Conclusions:

  • Dapagliflozin demonstrated a protective effect against osteoporosis in a T2DM rat model.
  • The mechanism may involve suppressing serum calcitonin and mitigating hyperglycemia-induced hypercalciuria.
  • Dapagliflozin appears to alleviate, rather than aggravate, diabetic osteoporosis by improving bone quality and reducing urinary calcium loss.
Keywords:
Sodium dependent glucose transporters 2 inhibitorZDF ratsbone microarchitecturedapagliflozintype 2 diabetes mellitus

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