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The skeletal effects of thiazolidinedione and metformin on insulin-resistant mice

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

To explore the skeletal effects and the potential underlying mechanisms of treatment with two thiazolidinediones (rosiglitazone and pioglitazone) or metformin in insulin-resistant mice, 24 female, 12-week-old C57BL6J ob/ob mice were evaluated according to the following treatment groups for 6 weeks: placebo group, pioglitazone group (Pio), rosiglitazone group (Rosi), and metformin group (Met). Bone mineral density (BMD), bone microarchitecture, bone histomorphometry, and expression of three phenotype-specific gene markers, including bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), and fatty acid-binding protein 4 (Fabp4), were compared across the four groups. At the femur, the Met group had the highest BMD (0.084 ± 0.001 g/cm2) and trabecular bone volume/total volume (0.644 ± 0.018 %) and the lowest trabecular spacing (Tb.Sp.) (0.143 ± 0.008 μm), whereas the Rosi group had lower BMD (0.076 ± 0.003 g/cm2) and a relatively higher degree of Tb.Sp. (0.173 ± 0.024 μm). A histomorphometric analysis revealed that in the Rosi group the number of adipocytes was fourfold higher than in the placebo group and fivefold higher than in the Met group, whereas the highest osteoid width and mineral apposition rate were found in the Met group (49.88 ± 48.53 μm and 4.46 ± 1.72 μm/day). Furthermore, the Rosi group displayed the highest level of Fabp4 gene expression, which was accompanied by normal expression levels of Bmp2 and Runx2. Seemingly, metformin is a bone-friendly antidiabetic drug. Rosiglitazone had adverse effects on the skeleton at the trabecular bone even in insulin-resistant mice, whereas no evidence of adverse effects was found for pioglitazone.

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Acknowledgments

We are grateful to Dr. Guo-Ying Zhu, Dr. Xiao Chen, Dr. Hui-Min Yan, and Dr. Hui Xie for their excellent and generous assistance. The study was supported by the Shanghai Science & Technology Development Fund (Project No. 08411963100) and the Shanghai Natural Science Foundation 11ZR1427300 (Science and Technology commission of Shanghai municipality).

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Authors and Affiliations

  1. Department of Central laboratory, Shanghai Tenth People’s Hospital affiliated with Shanghai Tongji University, 301 Yanchangzhong Road, 200072, Shanghai, China

    Ke-Sheng Wang, Mei-Ling Lu & Yong-Chun Yu

  2. Department of Endocrinology, Shanghai Tenth People’s Hospital affiliated with Shanghai Tongji University, Shanghai, China

    Hong Li, Chun-Jun Sheng, Xiao-Yun Cheng & Shen Qu

  3. Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People’s Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China

    Chun Wang & Jin-Wei He

  4. Emergency Department, Shanghai Sixth People’s Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China

    Sheng-Guang Chen

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  1. Chun Wang
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Correspondence to Yong-Chun Yu.

Additional information

C. Wang and H. Li contributed equally to this work.

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Wang, C., Li, H., Chen, SG. et al. The skeletal effects of thiazolidinedione and metformin on insulin-resistant mice. J Bone Miner Metab 30, 630–637 (2012). https://doi.org/10.1007/s00774-012-0374-0

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  • DOI: https://doi.org/10.1007/s00774-012-0374-0

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