Display options
Cite
McCarthy AD, Cortizo AM, Sedlinsky C. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy. World J Diabetes. 2016;7(6):122-33doi: 10.4239/wjd.v7.i6.122.
McCarthy, A. D., Cortizo, A. M., & Sedlinsky, C. (2016). Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy. World journal of diabetes, 7(6), 122-33. https://doi.org/10.4239/wjd.v7.i6.122
McCarthy, Antonio Desmond, et al. "Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy." World journal of diabetes vol. 7,6 (2016): 122-33. doi: https://doi.org/10.4239/wjd.v7.i6.122
McCarthy AD, Cortizo AM, Sedlinsky C. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy. World J Diabetes. 2016 Mar 25;7(6):122-33. doi: 10.4239/wjd.v7.i6.122. PMID: 27022443; PMCID: PMC4807302.
Copy Download .nbib Format: NLM
Share it on

World J Diabetes. 2016 Mar 25;7(6):122-33. doi: 10.4239/wjd.v7.i6.122.

Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy.

World journal of diabetes

Antonio Desmond McCarthy, Ana María Cortizo, Claudia Sedlinsky

Affiliations

  1. Antonio Desmond McCarthy, Ana María Cortizo, Claudia Sedlinsky, Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina.

PMID: 27022443 PMCID: PMC4807302 DOI: 10.4239/wjd.v7.i6.122

Abstract

Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or "diabetic osteopathy". These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint.

Keywords: AMP-activated kinase; Bone fractures; Diabetes mellitus; Metformin; Osteoporosis

References

  1. J Cell Physiol. 2009 Dec;221(3):740-9 - PubMed
  2. Diabetes Care. 2001 Jul;24(7):1192-7 - PubMed
  3. Biochem Soc Trans. 2003 Feb;31(Pt 1):216-9 - PubMed
  4. PLoS One. 2015 Jun 22;10(6):e0130480 - PubMed
  5. Drugs Today (Barc). 2008 Apr;44(4):303-14 - PubMed
  6. Biochem Biophys Res Commun. 2011 Jan 28;404(4):1004-9 - PubMed
  7. J Endocrinol. 2012 Mar;212(3):277-90 - PubMed
  8. Eur J Pharmacol. 2006 Apr 24;536(1-2):38-46 - PubMed
  9. Diabetologia. 1999 Aug;42(8):920-5 - PubMed
  10. BMC Cell Biol. 2007 Nov 29;8:51 - PubMed
  11. Bone Joint J. 2013 Nov;95-B(11):1575-80 - PubMed
  12. J Bone Miner Metab. 2012 Nov;30(6):630-7 - PubMed
  13. Diabetes Care. 2011 Nov;34(11):2474-6 - PubMed
  14. Curr Protein Pept Sci. 2008 Oct;9(5):478-92 - PubMed
  15. Calcif Tissue Int. 1991 Sep;49(3):155-60 - PubMed
  16. Biochem Biophys Res Commun. 2010 Apr 23;395(1):146-51 - PubMed
  17. Clin Sci (Lond). 2013 Apr;124(8):491-507 - PubMed
  18. J Bone Miner Metab. 2015 Mar;33(2):207-12 - PubMed
  19. Lancet. 1998 Sep 12;352(9131):854-65 - PubMed
  20. J Biol Chem. 2013 Apr 26;288(17):12187-96 - PubMed
  21. Endocrinology. 2002 Jun;143(6):2376-84 - PubMed
  22. J Clin Invest. 2013 Jul;123(7):2764-72 - PubMed
  23. J Diabetes Complications. 2010 Sep-Oct;24(5):334-44 - PubMed
  24. Osteoporos Int. 2013 Oct;24(10 ):2659-70 - PubMed
  25. Cell Biochem Funct. 2014 Jun;32(4):368-77 - PubMed
  26. J Bone Miner Res. 2009 Sep;24(9):1618-27 - PubMed
  27. Clin Sci (Lond). 2012 Mar;122(6):253-70 - PubMed
  28. FEBS J. 2013 Sep;280(17):4118-30 - PubMed
  29. Diabetologia. 2005 Jul;48(7):1292-9 - PubMed
  30. Eur J Pharmacol. 2014 Mar 15;727:8-14 - PubMed
  31. J Clin Invest. 2001 Oct;108(8):1167-74 - PubMed
  32. Diabetes. 2002 Jul;51(7):2074-81 - PubMed
  33. Biochem Biophys Res Commun. 2008 Oct 24;375(3):414-9 - PubMed
  34. Mediators Inflamm. 2014;2014:973986 - PubMed
  35. J Clin Invest. 2010 Jul;120(7):2355-69 - PubMed
  36. Exp Clin Endocrinol Diabetes. 2008 Jun;116(6):333-40 - PubMed
  37. Metabolism. 2005 Jun;54(6):829-34 - PubMed
  38. J Clin Endocrinol Metab. 2001 Jan;86(1):32-8 - PubMed
  39. J Diabetes Res. 2014;2014:453940 - PubMed
  40. J Pharm Pharmacol. 2008 Dec;60(12):1695-700 - PubMed
  41. J Clin Endocrinol Metab. 2010 Jan;95(1):134-42 - PubMed
  42. Diabetes Obes Metab. 2011 Nov;13(11):1036-46 - PubMed
  43. Eur J Pharmacol. 2011 Oct 15;668(3):477-85 - PubMed
  44. Cell Metab. 2015 Jun 2;21(6):799-804 - PubMed
  45. Endocrinology. 2004 Jan;145(1):401-6 - PubMed
  46. Endocrinology. 2005 Mar;146(3):1226-35 - PubMed
  47. J Periodontol. 2015 Jun;86(6):729-37 - PubMed
  48. Diabetes Care. 2008 Feb;31(2):199-203 - PubMed
  49. J Bone Miner Res. 2008 Aug;23(8):1334-42 - PubMed
  50. Diabetes. 2007 Aug;56(8):2062-9 - PubMed
  51. J Bone Miner Res. 2007 Sep;22(9):1317-28 - PubMed
  52. Lancet Diabetes Endocrinol. 2015 Jan;3(1):8-10 - PubMed
  53. J Bone Miner Res. 2010 Feb;25(2):211-21 - PubMed
  54. Bone. 2010 Aug;47(2):309-19 - PubMed
  55. Bone. 2010 Nov;47(5):926-37 - PubMed
  56. PLoS One. 2011;6(10 ):e25900 - PubMed
  57. Diabetes Res Clin Pract. 2013 Aug;101(2):177-86 - PubMed
  58. Osteoporos Int. 2010 Feb;21(2):195-214 - PubMed
  59. J Cell Biochem. 2011 Oct;112(10):2902-9 - PubMed
  60. Eur J Pharmacol. 2010 Jun 10;635(1-3):231-6 - PubMed
  61. Trends Endocrinol Metab. 2015 Jun;26(6):275-86 - PubMed
  62. Bone. 2011 Apr 1;48(4):885-93 - PubMed
  63. N Engl J Med. 2006 Dec 7;355(23):2427-43 - PubMed
  64. Eur J Endocrinol. 2012 Apr;166(4):711-6 - PubMed
  65. Endocr Rev. 2015 Apr;36(2):194-213 - PubMed

Publication Types