Zoledronic Acid Improves Bone Quality in the Streptozotocin-Induced Diabetes Rat through Affecting the Expression of the Osteoblast-Regulating Transcription Factors

Abstract

Aims To evaluate the short term effect of zoledronic acid on bone remodeling in the streptozotocin induced diabetes rats.

Materials and Methods Diabetes was induced by an injection of streptozotocin (60 mg/kg). The rats were treated with zoledronic acid (0.1 mg/kg) at the onset of diabetes (Z-I group) and 2 weeks later (Z-II group). Rats were sacrificed at the 1, 2, 3, 4 and 5 weeks after the onset of diabetes. Real–time PCR and western blot were performed to detect the expression of the following osteogenic gene mRNAs and their proteins: bone morphogenetic proteins 2 (BMP2), Runx2, Osterix and Noggin. The bone mineral density (BMD) and the mechanical resistance test was measured.

Results BMP2, Runx2 and Osterix mRNA and protein expression in group D had regulated down, while Noggin expression increased. Z-I treatment could reverse the results. However group Z-II showed only a transient reversing effect. On the 5^th week in group D, the BMD decreased, the bone trabecular distance increased, while the trabecular thickness and bone trabecular volume were reduced, the biomechanics index decreased significantly. Zoledronic acid treatment restored these alterations.

Conclusions Zoledronic acid administered in the early stage of the diabetes could prevent the osteopenia. The underlying mechanisms might be that zoledronic acid treatment reversed the effect of diabetes on the expression of osteoblast-regulating transcription factors: BMP2, Runx2 and Osterix.

Key words

bisphosphonates - osteopenia - diabetes mellitus

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