The Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis

Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period.

Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured.

Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Year	Entry
1987	Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units: report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res. December 1987;2(6):595-610.
1984	Lanyon LE, Rubin CT. Static vs dynamic loads as an influence on bone remodelling. J Biomech. 1984;17(12):897-905.
1993	Heaney RP. Is there a role for bone quality in fragility fractures? Calcif Tiss Int. February 1993;53(suppl 1):S3-S6.
2005	Thomsen JS, Laib A, Koller B, Prohaska S, Mosekilde L, Gowin W. Stereological measures of trabecular bone structure: comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies. J Microsc (Oxford). 2005;218(2):171-179.
2000	Turner CH, Hsieh Y, Müller R, Bouxsein ML, Baylink DJ, Rosen CJ, Grynpas MD, Donahue LR, Beamer WG. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res. June 2000;15(6):1126-1131.
1998	Turner CH. Three rules for bone adaptation to mechanical stimuli. Bone. November 1998;23(5):399-407.
2005	de Liefde II, van der Klift M, de Laet CEDH, van Daele PLA, Hofman A, Pols HAP. Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int. December 2005;16(12):1713-1720.
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1998	Ito M, Nakamura T, Matsumoto T, Tsurusaki K, Hayashi K. Analysis of trabecular microarchitecture of human iliac bone using microcomputed tomography in patients with hip arthrosis with or without vertebral fracture. Bone. August 1998;23(2):163-169.
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2001	Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001.
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Year

Entry

1987

Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units: report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res. December 1987;2(6):595-610.

1984

Lanyon LE, Rubin CT. Static vs dynamic loads as an influence on bone remodelling. J Biomech. 1984;17(12):897-905.

1993

Heaney RP. Is there a role for bone quality in fragility fractures? Calcif Tiss Int. February 1993;53(suppl 1):S3-S6.

2005

Thomsen JS, Laib A, Koller B, Prohaska S, Mosekilde L, Gowin W. Stereological measures of trabecular bone structure: comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies. J Microsc (Oxford). 2005;218(2):171-179.

2000

Turner CH, Hsieh Y, Müller R, Bouxsein ML, Baylink DJ, Rosen CJ, Grynpas MD, Donahue LR, Beamer WG. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res. June 2000;15(6):1126-1131.