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Horm Metab Res 2013; 45(01): 1-8
DOI: 10.1055/s-0032-1321874
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Thiazolidinediones (TZDs) Affect Osteoblast Viability and Biomarkers Independently of the TZD Effects on Aromatase

A. Seth
1   The Friedman Diabetes Institute, Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, New York, USA
,
V. Sy
1   The Friedman Diabetes Institute, Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, New York, USA
,
A. Pareek
1   The Friedman Diabetes Institute, Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, New York, USA
,
P. Suwandhi
1   The Friedman Diabetes Institute, Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, New York, USA
,
Z. Rosenwaks
2   Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University New York, New York, USA
,
L. Poretsky
1   The Friedman Diabetes Institute, Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, New York, USA
,
D. Seto-Young
1   The Friedman Diabetes Institute, Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, New York, USA
› Author Affiliations
Further Information

Publication History

received 16 March 2012

accepted 04 July 2012

Publication Date:
09 August 2012 (online)

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Abstract

Thiazolidinediones (TZDs) are insulin sensitizers used for treatment of diabetes. We have previously reported that TZDs reduce estrogen synthesis by inhibiting aromatase activity in human granulosa cells (HGC). Multiple clinical trials demonstrated that TZDs increase the risk of fractures in postmenopausal women with type 2 diabetes. We studied mouse osteoblasts alone or in a co-culture with HGC to determine whether TZD inhibition of aromatase plays a role in their effects on bone metabolism. Mouse osteoblasts were cultured with and without HGC, and incubated in a medium with or without testosterone, pioglitazone or rosiglitazone. Cell growth, oleic acid uptake, alkaline phosphatase activity, and osteocalcin production were measured. TZDs inhibited estradiol production by up to 84% in HGC/mouse osteoblast co-cultures. TZDs induced mouse osteoblast death and increased oleic acid uptake. TZDs also inhibited alkaline phosphatase activity (58–75%, p<0.046) and osteocalcin production (52–75%, p<0.031). For all the parameters, there were no significant differences between the osteoblast cultures alone and the HCG/osteoblast co-cultures. TZD effects on osteoblast viability, oleic acid uptake, alkaline phosphatase and osteocalcin production are independent of their effects on aromatase.

Key words

osteoblast - oral antidiabetic drugs - bone homeostasis
 

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