title: The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing.
abstract: CONCLUSIONS
  The present study shows no adverse effects of the anti-diabetic drug metformin on bone mass and fracture healing in rodents but demonstrates that metformin is not osteogenic in vivo, as previously proposed.
  
  
  BACKGROUND
  In view of the increased incidence of fractures in patients with type 2 diabetes mellitus (T2DM), we investigated the effects of metformin, a widely used T2DM therapy, on bone mass and fracture healing in vivo using two different rodent models and modes of metformin administration.
  
  
  METHODS
  We first subjected 12-week-old female C57BL/6 mice to ovariectomy (OVX). Four weeks after OVX, mice received either saline or metformin administered by gavage (100 mg/kg/daily). After 4 weeks of treatment, bone micro-architecture and cellular activity were determined in tibia by micro-CT and bone histomorphometry. In another experiment, female Wistar rats aged 3 months were given only water or metformin for 8 weeks via the drinking water (2 mg/ml). After 4 weeks of treatment, a mid-diaphyseal osteotomy was performed in the left femur. Rats were sacrificed 4 weeks after osteotomy and bone architecture analysed by micro-CT in the right tibia while fracture healing and callus volume were determined in the left femur by X-ray analysis and micro-CT, respectively.
  
  
  RESULTS
  In both models, our results show no significant differences in cortical and trabecular bone architecture in metformin-treated rodents compared to saline. Metformin had no effect on bone resorption but reduced bone formation rate in trabecular bone. Mean X-ray scores assessed on control and metformin fractures showed no significant differences of healing between the groups. Fracture callus volume and mineral content after 4 weeks were similar in both groups.
  
  
  CONCLUSIONS
  Our results indicate that metformin has no effect on bone mass in vivo or fracture healing in rodents.
authors: Department of Comparative and Biomedical Sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU, UK.
authors: J
authors: J
authors: Jeyabalan
authors: B
authors: B
authors: Viollet
authors: P
authors: P
authors: Smitham
authors: S A
authors: SA
authors: Ellis
authors: G
authors: G
authors: Zaman
authors: C
authors: C
authors: Bardin
authors: A
authors: A
authors: Goodship
authors: J P
authors: JP
authors: Roux
authors: M
authors: M
authors: Pierre
authors: C
authors: C
authors: Chenu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005264:Femoral Fractures / Q000503:physiopathology; D005269:Femur / Q000201:enzymology; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology*; D008687:Metformin / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000503:physiopathology; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D055372:AMP-Activated Protein Kinases
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