**3. Conclusions**

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 be attributed to chronic, high-dose glucocorticoid administration in humans (van Staa et al., 2001). Prior and current exposure to glucocorticoids increases the risk of fractures beyond that explained by values of BMD (Civitelli & Ziambaras, 2008). Pharmacological intervention for prevention of glucocorticoid-induced osteoporosis is needed depending on dose, expected duration of treatment, age and gender of the patient, and sometimes BMD at the start of the glucocorticoid therapy. At present, calcium and vitamin D3 supplementation are considered as important support for the prevention of glucocorticoid-induced osteoporosis (Williams et al., 2004). Bisphosphonates are largely used to avoid bone loss and are cost effective in certain subgroups of patients depending on age, gender, glucocorticoid dose, and previous fracture history (Williams et al., 2004; Prinsloo & Hosking, 2006). Unfortunately, calcium and vitamin D3 supplementation may not be enough to stave off bone deterioration and bisphosphonates have safety risks associated with long-term use, such as esophageal burns, bone and muscular pain (Ettinger et al., 1998; Wysowski & Chang, 2005). Osteonecrosis of the jaw, although rare and found primarily in cancer patients undergoing dental surgery, is a very serious and debilitating side effect of bisphosphonate use (Durie et al., 2005). Therefore, a safe and effective treatment for the prevention of bone loss and osteonecrosis of the femoral head in glucocorticoid-treated subjects is still needed.

Collectively, our results strongly suggest that genistein might be a new potential therapy for the prevention of glucocorticoid-induced osteoporosis, the most important secondary cause of osteoporosis in humans. And in the minority of cases, genistein may prevent necrotic deterioration of the femoral head. Usually, drugs used in management of osteoporosis have been classified as predominantly 'antiresorptive agents' or as 'bone-forming agents', but, on the basis of the present results, genistein might represent the first therapy to overcome this classification combining a powerful bone-forming as well as an anti-resorptive activity.
