Abstract:

BACKGROUND: Zoledronic acid is a new generation of diphosphate, which is the third generation of osteoporosis drugs. It is widely used to treat diseases related to increase of bone absorption in clinic. The effect of zoledronic acid on osteoclast has reached consensus, but its effect on osteoblast remains in dispute.  
OBJECTIVE: To observe the effect of zoledronic acid on the proliferation, differentiation and the mRNA expression of osteoprotegerin (OPG) and tumor necrosis factor α (TNF-α) of rat osteoblasts.
METHODS: The osteoblasts isolated from the calvaria of neonatal SD rats were cultured with different concentrations of zoledronic acid. The final concentration of zoledronic acid in the experimental group ranged from 10^-5-10^-9 mol/L. At 3, 5, and 7 days after zoledronic acid intervention, MTT colorimetric assay was used to measure the absorbance to detect the effect of zoledronic acid on the proliferation of osteoblasts. p-nitrophenyl phosphate approach method was used to detect the activities of alkaline phosphatase, while RT-PCR was used to detect OPG and TNF-α mRNA expression.
RESULTS AND CONCLUSION: Zoledronic acid at the concentration of 10^-5 mol/L could inhibit the proliferation of osteoblasts, but it had no effect at concentration of 10^-7-10^-9 mol/L. Zoledronic acid at concentration of 10^-5-10^-9  mol/L could up-regulate the OPG mRNA expression, but down-regulate TNF-α mRNA expression. Zoledronic acid at low concentration cannot influence the proliferation and differentiation of osteoblasts; whereas, it can inhibit bone resorption by regulating the OPG and TNF-α mRNA expression.