Removal of zoledronic acid by calcium phosphate adsorbents

Nowadays, dentists are facing with many bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients as the number of patients receiving nitrogen-containing bisphosphonates (N-BPs) is dramatically increasing around the world. One possible cause of BRONJ may involve an increased accumulation of N-BPs to cytotoxic levels in the jawbone. Thus, to reduce the risk of BRONJ, it is possible that adsorption of unbound N-BP molecules by calcium phosphate adsorbents may help decrease N-BP uptake into the target cells, thus preventing the cytotoxicity of N-BP. The present study aimed to compare the zoledronic acid (ZA) adsorption efficacies of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) and to determine the factors influencing their adsorption abilities. Two calcium phosphate adsorbents, i.e., HA and β-TCP, were characterized by scanning electron microscopy (SEM), attenuated total reflection-Fourier transform infrared (ATR-FTIR) and laser light scattering particle size analysis. HA and β-TCP adsorbents, used at varied quantities, were individually immersed in the ZA solution as a function of incubation time, to study the ZA adsorption efficacy. The remaining ZA concentration after a given adsorption time was determined using high-performance liquid chromatography (HPLC). The cytoprotection was assessed using an in vitro periodontal ligament (PDL) cells cytotoxicity test. The chemical interaction between each adsorbent and ZA was examined by scanning electron microscopy/energy(2)dispersive X-ray spectroscopy (SEM/EDX) and ATR-FTIR. The results showed thatthe particle size distributions of HA and β-TCP were not remarkably different. In termsof ZA adsorption efficacy, 0.02 g of HA possessed the highest adsorption efficiency,approximately 96%, regardless of the adsorption time, whereas 0.005 g of β-TCPshowed the lowest efficacy, in the range of approximately 31-41% after 1h and 24 h ofadsorption. The amount of each adsorbent used, but not the adsorption time, seemed tosignificantly affect the adsorption efficacy. Moreover, a chemical interaction betweenZA and HA, but not β-TCP, was likely occurred. It was also found that HA, but not β-TCP, appeared to rescue the number of viable PDL cells, with the 0.02 g HA groupsshowing the most cytoprotective effects, against ZA regardless of the incubation time.In conclusion, despite similar shape and size of the particles of the calcium phosphatesused, HA provided a much higher ZA adsorption efficiency than β-TCP did, possiblythrough a higher chemical bonding to ZA. In addition, HA also markedly rescued thecytotoxicity of ZA to PDL cells. This suggested that HA is a promising bone substitutematerial candidate for patients with a high risk to develop BRONJ.