科研之友
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摘要
Zoledronic acid is regarded as the most potent bisphosphonate and is widely used in patients with osteoporosis; however, its side effects, including acute-phase reactions, gastrointestinal complaints, renal dysfunction and bisphosphonate-associated osteonecrosis impair the safety and quality of life of patients. The present study was designed to determine the minimal effective concentration of zoledronic acid through testing the dose-dependent effects of zoledronic acid on osteoclast suppression. A primary culture of bone marrow mononuclear cells obtained from C57 mice (age, 6 weeks) was established and induced to form osteoclasts. The number of multinuclear cells was determined by tartrate-resistant acid phosphatase staining and compared among cultured marrow cells treated with different concentrations of zoledronic acid. Furthermore, the cellular properties, including adhesion, migration and bone resorption, were compared at the minimal effective concentration. At a concentration of 1x10(-6) mol/l, zoledronic acid significantly inhibited the formation of osteoclasts. This inhibitory effect was further enhanced at the concentration of 1x10(-5) mol/l. However, the inhibitory effect of zoledronic acid tapered at the concentration of 1x10(-4) mol/l and there was no further dose-dependent increase. In addition, the concentration of 1x10(-6) mol/l was sufficient to alter cellular functions, including cell adhesion, migration and bone resorption. In conclusion, zoledronic acid was effective in reducing osteoclast formation and suppressing cellular functions. The minimal effective concentration of zoledronic acid in vitro was 1 mu mol/l. Based on these results, a comparable dosage should be explored in clinical applications.
- 出版日期2018-6
- 单位河北医科大学
