Those reports agree that bisphosphonate therapy promotes Cl-amidine research buy osseous repair by enhancing formation, mineralization, and mechanical strength of callus, but also slows callus remodeling. Hence, our result of high bone fill by ALN/DEX is consistent with the literature. Despite the positive impact on tibial wound healing, in contrast, ALN/DEX impaired tooth extraction wound Dasatinib order healing in the jaw and resulted in a greater incidence of exposed bone. The combined use of bisphosphonates and steroid

has been demonstrated to be associated with the development of necrotic lesions in rats [18, 19]. The impaired extraction wound healing by ALN/DEX observed in our study is consistent with these reports. It should be mentioned that although the bisphosphonate/steroid treatment impaired tooth extraction wound healing in rats, such a drug combination does not always hinder wound healing in other animals [28]. The difference in osseous healing between the tibia and jaw may be similar to what is seen in patients on antiresorptive therapy. ONJ uniquely occurs in the jaw but not in long bones [29]. Tooth extraction

wounds are different from tibial osseous wounds AZD0156 mouse in that (1) they are open wounds exposed to the oral cavity where numerous oral pathogens inhabit and dense bacterial colonization occurs [30], (2) the extraction wounds are subjected to repeated mechanical trauma from chewing, (3) the extraction sockets are surrounded by dense bundle bone while the tibial wounds are exposed to the abundance of the bone marrow milieu, (4) the embryologic origin of the maxillae and mandibles (pharyngeal arch 1) is distinct from long bones [31], and (5) the bone formation pattern of the alveolar bone is different from that of long bones (intramembranous vs. endochondral bone formation) [32]. Considering these differences, tooth extraction wound healing appears to be distinct from long bone wound healing. However, the exact mechanism of the different healing responses between the tibia and jaw is unclear. The etiopathological role of oral bacteria in ONJ has been proposed; when bacterial infection, such as periodontitis, was experimentally induced in rats receiving

bisphosphonates, necrotic lesions developed, however, no such lesions occurred in rats without bisphosphonate therapy [33, 34]. In support of this hypothesis, Lopez-Jornet et al. reported that antibiotic Rapamycin ic50 administration prior to tooth extractions in rats on the combination of bisphosphonates and DEX significantly reduced the incidence of necrotic lesions [35]. Whether bisphosphonate treatment exacerbates bacterial infection or not was studied using a rat model of infectious osteomyelitis [36]. In this study gentamycin-sensitive Staphylococcus aureus-treated implants were placed in rat tibiae with or without ALN treatment. High-grade infection and necrotic bone formation were found with ALN treatment, while neither infection nor necrotic bone was noted with placebo.