Abstract
This study investigates the effects of zoledronic acid (ZA) and compressive force on osteoblast functions, to elucidate the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). MC3T3-E1 cells were exposed to ZA (1, 10 and 100 µM) to evaluate the effects of ZA on cell proliferation. Furthermore, to investigate the influence of ZA with or without compressive force on osteoblast differentiation, real-time polymerase chain reaction and Alizarin Red S staining were performed. ZA concentrations > 10 μM were highly cytotoxic to MC3T3-E1 cells. Combining 1-μM ZA with compressive force influenced expression levels of osteoblast-related genes and matrix mineralization. The inhibitory effects of ZA on cell proliferation and the combination of ZA and compressive force on osteoblast differentiation may contribute to the pathogenesis of MRONJ.
Highlights
Bisphosphonates (BPs) have seen wide use in the treatment of various bone diseases [1,2]
Several reports have demonstrated that diabetes mellitus, severe periodontitis and traumatic tooth extraction represent risk factors for the progression of medication-related osteonecrosis of the jaw” (MRONJ) [6,7,8]
We investigated the effects of Zoledronic acid (ZA) and compressive force on osteoblast functions, to clarify the possible pathogenesis of MRONJ
Summary
Bisphosphonates (BPs) have seen wide use in the treatment of various bone diseases [1,2]. Zoledronic acid (ZA) is considered one of the most intensive and effective BPs, and is widely used in clinical practice for the treatment of various bone diseases. Despite the many beneficial effects of BPs, bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a problem, and the number of identified BRONJ cases appears to be increasing rapidly. Compressive force as seen in traumatic occlusion, bruxism and bite force from ill-fitting dentures may contribute to the pathogenesis of MRONJ. The effects of compressive force and ZA on osteoblast proliferation and differentiation remain uncertain. We investigated the effects of ZA and compressive force on osteoblast functions, to clarify the possible pathogenesis of MRONJ
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