PMID- 31781028
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201005
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 10
DP  - 2019
TI  - Dapagliflozin Attenuates Hyperglycemia Related Osteoporosis in ZDF Rats by 
      Alleviating Hypercalciuria.
PG  - 700
LID - 10.3389/fendo.2019.00700 [doi]
LID - 700
AB  - Recent studies showed that in patients with type 2 diabetes mellitus (T2DM), 
      Sodium-dependent glucose transporters 2 inhibitor (SGLT2I) may cause potential 
      adverse effects on the skeleton such as increasing the risk of fracture. This 
      risk is possibly mediated by effects induced by all SGLT2I class drugs, but 
      whether Dapagliflozin aggravates osteoporosis in patients with T2DM remains 
      controversial. Therefore, we designed this study to explore how Dapagliflozin 
      affects the metabolism and the quality of bone in T2DM animal models. The effect 
      of Dapagliflozin on the skeleton was evaluated on male ZDF (Zucker Diabetic 
      Fatty) rats-a rat model of diet induced spontaneous T2DM. Dapagliflozin was 
      administrated via gavage at the dosage of 10 mg/kg/day. Bone tissue mineral 
      density and the microarchitecture of tibiae were measured with micro-CT and 
      biomechanics characteristic of the femora were tested using a three-point bending 
      test. Serum bone biomarkers and other metabolic parameters were also tested via 
      ELISA or other assays. Our results found that diabetic rats demonstrated symptoms 
      of osteoporosis and Dapagliflozin could help to alleviate these defections caused 
      by diabetes. Compared to the negative controls, the serum CT (calcitonin) level 
      in ZDF rats as well as the uric calcium and phosphate levels were elevated, and 
      these symptoms were alleviated by Dapagliflozin. Tibiae of Dapagliflozin treated 
      rats demonstrated decreased cortical tissue mineral density while trabecular 
      tissue mineral density and mean bone mineral density received a rise when 
      compared to the matched controls. ZDF rats also showed defections in femora 
      stiffness which could be relieved by Dapagliflozin administration. The mechanism 
      of Dapagliflozin affecting bone quality is possibly connected to the suppression 
      of serum calcitonin and excretion of calcium via urine rose by hyperglycemia. In 
      conclusion, Dapagliflozin can prevent osteoporosis in ZDF rats by alleviating 
      hypercalciuria.
CI  - Copyright (c) 2019 Wang, Cheng, Yang, An, Zhang, Chen and Yang.
FAU - Wang, Ji-Yu
AU  - Wang JY
AD  - Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Cheng, Yan-Zhen
AU  - Cheng YZ
AD  - Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Yang, Shuang-Li
AU  - Yang SL
AD  - Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical 
      University, Guangzhou, China.
AD  - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of 
      GuiZhou Medical University, Kaili, China.
FAU - An, Min
AU  - An M
AD  - Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Zhang, Hua
AU  - Zhang H
AD  - Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Chen, Hong
AU  - Chen H
AD  - Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical 
      University, Guangzhou, China.
FAU - Yang, Li
AU  - Yang L
AD  - Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical 
      University, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20191105
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
EIN - Front Endocrinol (Lausanne). 2020 Sep 02;11:524. PMID: 33013683
PMC - PMC6856656
OTO - NOTNLM
OT  - Sodium dependent glucose transporters 2 inhibitor
OT  - ZDF rats
OT  - bone microarchitecture
OT  - dapagliflozin
OT  - type 2 diabetes mellitus
EDAT- 2019/11/30 06:00
MHDA- 2019/11/30 06:01
PMCR- 2019/01/01
CRDT- 2019/11/30 06:00
PHST- 2019/05/05 00:00 [received]
PHST- 2019/09/27 00:00 [accepted]
PHST- 2019/11/30 06:00 [entrez]
PHST- 2019/11/30 06:00 [pubmed]
PHST- 2019/11/30 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2019.00700 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2019 Nov 5;10:700. doi: 10.3389/fendo.2019.00700. 
      eCollection 2019.