Preventative effects of metformin on glucocorticoid-induced osteoporosis in rats

  • Jianrong Zhao
  • Yingbin Li
  • Hao Zhang
  • Dongying Shi
  • Qingnan Li
  • Li ZuoEmail author
  • Yan MengEmail author
Original Article


This study evaluated the preventative effects of metformin (Met) on glucocorticoid (GC)-induced osteoporosis in a rat model, compared with alendronate (Aln). Twenty-eight 3-month-old female Sprague–Dawley rats were randomly assigned into four groups: normal control (Ctr), methylprednisolone (MP, 13 mg/kg/day, sc, 5 days per week), MP plus Aln orally (1 mg/kg/day), and MP plus Met orally (200 mg/kg/day). After 9 weeks, serum bone metabolic biochemistry, bone densitometry and histomorphometry were performed. The GC-induced osteoporosis model was characterized by decreased osteocalcin, increased tartrate-resistant acid phosphatase-5b (TRAP-5b), and decreased bone mineral density (BMD) in the femur and fifth lumbar vertebra (L5). Histomorphometrically, MP significantly decreased trabecular bone volume, decreased bone formation and increased bone resorption in proximal metaphysis, compared with the controls. Aln and Met increased the BMDs of femur (0.305 ± 0.011 vs. 0.280 ± 0.012, P < 0.05; 0.304 ± 0.019 vs. 0.280 ± 0.012, P < 0.05) and L5 (0.399 ± 0.029 vs. 0.358 ± 0.022, P < 0.05; 0.397 ± 0.022 vs. 0.358 ± 0.022, P < 0.05), compared with the model group. Met increased osteocalcin and decreased TRAP-5b, but Aln only decreased TRAP-5b, compared with model group. In histomorphometry of tibial proximal metaphysis, Aln and Met increased trabecular bone volume (39.21 ± 2.46 vs. 30.98 ± 5.83, P < 0.05; 38.97 ± 5.56 vs. 30.98 ± 5.83, P < 0.05), while Met increased the bone formation dynamic parameters and decreased bone resorption dynamic parameters, but Aln just decreased bone resorption dynamic parameters, compared with model group significantly. These findings suggest that metformin prevents GC-induced bone loss by suppressing bone resorption and stimulating bone formation in trabecular bone. The action mode of metformin was different from alendronate, which only suppressed bone resorption.


Metformin Glucocorticoid-induced osteoporosis Histomorphometry Alendronate Rats 



We thank Dr. Ping Sun for her kind help in facilitating the cooperation among the facilities. This work was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region, China (No. 2014BS0807), the Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region, the Beijing Natural Science Foundation (No. 7162193), the Innovative Talents Group Foundation of Nephrology Department, Affiliated Hospital, Inner Mongolia Medical University of the Fifth Inner Mongolia ‘Prairie Meritocrat’ Project, and the Doctorial Scientific Research Starting Foundation of the Affiliated Hospital, Inner Mongolia Medical University (No. NYFYBS2015013).

Compliance with ethical standards

Conflict of interest

All the authors have no conflicts of interest.


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Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NephrologyThe Affiliated Hospital of Inner Mongolia Medical UniversityHohhotPeople’s Republic of China
  2. 2.Guangdong Legend Pharmaceutical Technology Co., Ltd.JiangmenPeople’s Republic of China
  3. 3.School of DentistryHubei University of MedicineShiyanPeople’s Republic of China
  4. 4.Guangdong Laboratory Animals Monitoring Institute and Key Laboratory of Guangdong Laboratory AnimalsGuangzhouPeople’s Republic of China
  5. 5.The Center for New Drug Function Research, School of Life Science and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhouPeople’s Republic of China
  6. 6.Department of NephrologyPeking University People’s HospitalBeijingPeople’s Republic of China

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