**4. References**

296 Basic and Clinical Endocrinology Up-to-Date

clarifying the putative antiresorptive effect being a non-apoptotic process, rather than an apoptotic process induced in antiresorptive therapy with bisphosphonates. Other mechanisms of genistein binding to glucocorticoid receptors have also been implicated.

**% of change vs vehicle**

**% of change vs vehicle**

**Bone ALP**

**A B**

**methylprednisolone methylprednisolone**

**C**

**% of change vs vehicle**

 **+ genistein**

**17.5 CTX**

**methylprednisolone methylprednisolone**

Fig. 4. A-C: Effects of aglycone genistein on serum bone-alkaline phosphatase (b-ALP), osteoprotegerin (OPG) and collagen C-telopeptides (CTX). Data are shown as % of variation from vehicle treated animals. b-ALP: \* *p*<0.005 vs methylprednisolone. OPG: \**p*<0.001 vs.

It has been demonstrated that genistein inhibits glucocorticoid receptor transactivation and may also induce a proteosomal degradation of the glucocorticoid receptor complex *via* the p53 and ubiquitin pathways (Kinyamu & Archer 2003). Another mechanism might involve genistein activity as a tyrosine kinase inhibitor *via* the limitation of the subcellular nuclear transport and the recycling of the glucocorticoid receptors, blunting in turn the effects of

Several studies and reports show a decrease in BMD and an increased risk of fractures during glucocorticoid use as well as an increase in osteonecrosis with chronic steroid use. Approximately 30% of all fractures of the hip and almost half of all fractures of the spine can

 **+ genistein**

\*

**methylprednisolone methylprednisolone**

 **+ genistein**

**0.0 2.5 5.0 7.5 10.0 12.5 15.0**

methylprednisolone. CTX: \**p*<0.001 vs. methylprednisolone.

glucocorticoids on bone (Yang et al., 1997).

**3. Conclusions** 

\*


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**Part 8** 

**Chronic Renal Disease and Endocrinology** 

