Genistein prevents bone loss in type 2 diabetic rats induced by streptozotocin

Diabetic osteoporosis has become a severe public health problem in the aging societies. Genistein has been reported to play an important role in preventing and treating metabolic diseases via its anti-inflammatory, antioxidant, anti-estrogenic, and estrogen-like functions.

We aimed to investigate whether genistein exerts bone-protective effect on diabetic rats induced by 35 mg/kg streptozotocin (STZ) plus a 4-week high-fat diet.

Sprague-Dawley rats were randomly divided into four groups: (1) control group, (2) type 2 diabetes mellitus (T2DM) model group, (3) T2DM with 10 mg/kg genistein, and (4) T2DM with 30 mg/kg genistein. After an 8-week treatment with genistein, the femurs, tibias, and blood were collected from all rats for further analysis.

Genistein at 10 mg/kg showed little effect on diabetic osteoporosis, whereas genistein at 30 mg/kg significantly improved glucose and bone metabolisms compared with diabetic rats. Our results showed that 30 mg/kg genistein significantly increased bone mineral density, serum osteocalcin, and bone alkaline phosphatase. Genistein also effectively lowered fasting blood glucose, tartrate-resistant acid phosphatase 5b, tumor necrosis factor-α, interleukin-6, and numbers of adipocytes and osteoclasts. Compared with the T2DM group, protein levels of receptor activator of nuclear factor κB ligand (RANKL) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were decreased, while protein levels of osteoprotegerin (OPG), β-catenin, and runt-related transcription factor 2 (Runx-2) were increased after genistein intervention.

Genistein could effectively improve abnormal bone metabolism in STZ-induced diabetic rats; the underlying molecular mechanisms might be related to OPG/RANKL, PPAR-γ, and β-catenin/Runx-2 pathways.