PLoS ONE (Jan 2015)

Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.

  • Raul Hernandes Bortolin,
  • Bento João da Graça Azevedo Abreu,
  • Marcela Abbott Galvão Ururahy,
  • Karla Simone Costa de Souza,
  • João Felipe Bezerra,
  • Melina Bezerra Loureiro,
  • Flávio Santos da Silva,
  • Dáfiny Emanuele da Silva Marques,
  • Angélica Amanda de Sousa Batista,
  • Gisele Oliveira,
  • André Ducati Luchessi,
  • Valéria Morgiana Gualberto Duarte Moreira Lima,
  • Carlos Eduardo Saraiva Miranda,
  • Marcus Vinicius Lia Fook,
  • Maria das Graças Almeida,
  • Luciana Augusto de Rezende,
  • Adriana Augusto de Rezende

DOI
https://doi.org/10.1371/journal.pone.0125349
Journal volume & issue
Vol. 10, no. 5
p. e0125349

Abstract

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Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days) type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM), and T1DM plus zinc supplementation (T1DMS). Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus), and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic and protective effect of zinc under chronic diabetic conditions. Furthermore, these results indicate that zinc supplementation could act as a complementary therapy in chronic T1DM.