Protective effect of genistein aglycone on the development of osteonecrosis of the femoral head and secondary osteoporosis induced by methylprednisolone in rats

Abstract

Glucocorticoid (GC)-induced osteoporosis (GIO) is the most important secondary cause of bone loss. Clinical evidence suggests a role for genistein (GEN) aglycone in the prevention of osteoporosis. We investigated whether GEN could prevent GIO as well as the development of osteonecrosis in the femoral head using an experimental rat model. A total of 28 female SpragueDawley rats were used in the study. GIO and osteonecrosis were induced by daily s.c. injections of 30 mg/kg of methylprednisolone (MP; nZ7). Another group of animals (MPCGEN; nZ7) concomitantly received MP (30 mg/kg per s.c.) and GEN aglycone (5 mg/kg per i.p.) for 60 days. Control animals were administered daily with vehicle (VEH) or GEN (5 mg/kg per i.p.) only. At the beginning and end of the treatment, animals were examined for bone mineral density (BMD) and bone mineral content (BMC). After killing, serum was collected to determine bone-alkaline phosphatase (b-ALP), carboxyterminal collagen crosslink (CTX) and osteoprotegerin (OPG) levels. Femurs were removed and tested for breaking strength and bone histology analyzed for structural quality of the femoral neck. GEN aglycone prevented bone loss as measured by BMD and BMC. Moreover, GEN significantly increased the bone formation markers b-ALP and OPG, reduced the bone resorption marker CTX and statistically maintained comparable strength versus the VEH only group. Finally, histological scoring revealed a protective effect of GEN on bone structure statistically comparable with the VEH control animals. Results suggest that the GEN aglycone might be a preventive treatment for GIO and complications of osteonecrosis with long-term GC treatment.

Premature T cell senescence in Ovx mice is inhibited by repletion of estrogen and medicarpin: a possible mechanism for alleviating bone loss

“…We hypothesize that Ovx increases the production of CD4 + CD28null premature senescent cells, and these cells secrete inflammatory cytokines like TNF-α which in turn enhance bone resorption. Additionally, phytoestrogens confer substantial benefits to bone health without posing the risk of cancer associated with HRT [19,20]. Recently, we have shown bone conserving effect of medicarpin (Med), a pterocarpantype phytoalexin present in dietary legume, in Ovx mice, suggesting its E2-"like" effect on bone.…”

Genistein Aglycone Demonstrates a Protective and Reversible Effect on the Development of Steroid-Induced Secondary Osteoporosis and Increases Bone Breaking Strength in Rats

“…In our study (Figure 1), genistein succeeded in preventing osteoporosis and osteonecrosis of the femoral head when co-administered with the glucocorticoid. The isoflavone statistically maintained bone mineral density (Figure 2) and content (Bitto et al, 2009) over the methylprednisolone-treated group and showed comparable efficacy with the vehicle group. Genistein co-administered with methylprednisolone also statistically maintained femoral bone's resistance to rupture compared with the methylprednisolone group ( Figure 3C) and preserved the normal architecture of cartilage as well as both cortical and trabecular bones with a well-organized matrix in femoral head (Figure 3 A and B).…”

“…Once osteonecrosis occurs, glucocorticoids also cause inhibition of bone regeneration (Takano-Murakami et al, 2009). In a rat model, we studied genistein preservative effects on methylprednisolone-induced bone loss and osteonecrosis of the femoral head (Bitto et al, 2009). In our study (Figure 1), genistein succeeded in preventing osteoporosis and osteonecrosis of the femoral head when co-administered with the glucocorticoid.…”

Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate

“…However, the therapeutic use of GCs in the management of immunosuppression following organ transplantation or of inflammatory diseases is always accompanied by substantial adverse outcomes including diabetes and obesity as well as bone loss, which is referred to in this case as GC-induced osteoporosis (GIOP) (3)(4)(5). Bone loss induced by GCs occurs early and progresses at a fast rate becoming significant within the first 6 months (6). Previous studies have demonstrated that the long-term administration of GCs resulted in the development of osteoporosis in approximately 50% of patients with asthma (7).…”