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Data arising from the recent literature directed the researchers to study on the degree and extent of bisphosphonate toxicity on oral mucosa in further detail. The aim of this study is to determine the half maximal inhibitory concentration of pamidronate (PAM) and alendronate (ALN) on human gingival fibroblasts in vitro using 3-[4.5-thiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) assay and to evaluate the effects of both agents on the proliferation and apoptotic indices. Cells used in the study were generated from human gingival specimens and divided into alendronate ( n = 240), PAM ( n = 240), and control groups ( n = 60). Based on the MTT assay results, 10−4, 10−5, 10−6, and 10−7 M concentrations of both drugs were administered and the effects were evaluated for 6, 12, 24, 48, or 72 h periods. An indirect immunofluorescence technique was used to evaluate apoptotic (anti-caspase 3) and proliferation (anti-Ki67) indices. Toxicity of both PAM and ALN was found to be the most potent at 10−4–10−5 M range. The apoptotic index of PAM group was found to be significantly higher than ALN group for all concentrations especially at 24 h incubation time ( p < 0.05). The decrease in the proliferation index was found similar in first 48 h for both drugs; however, after 72 h of incubation decrease in proliferation index in PAM group was found to be significantly higher ( p < 0.05). Micromolar concentrations of not only PAM but also ALN rapidly affect cells generated from human oral gingival tissue by inducing apoptosis together with inhibition of proliferation. Cytotoxic effects of both ALN and PAM on primary human gingival fibroblasts, which cause significant changes in apoptotic and proliferative indices as shown in this in vitro study, suggests that the defective epithelialization of oral mucosa is possibly a major factor on the onset of bisphosphonate-related osteonecrosis of the jaw cases.

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In this study, three-dimensional modeling and finite element analysis were used to evaluate and compare the stability of Le Fort I osteotomy fixed with titanium and resorbable fixation systems under molar and incisor bite forces. A three-dimensional model of 5-mm advanced hemimaxilla was generated. Contact analyses between the upper and lower segments were prescribed. Two L-plates were inserted on this model via simulation. Displacement, principal stresses, and principal elastic strains were evaluated under 44-N, 125-N incisor and, 250-N molar bite forces. These results suggest that Le Fort I osteotomies fixed with titanium miniplates and screws were stable under all tested forces. However, in resorbable group, under incisor bite forces greater than 44 N, there is a great risk of plate fracture, screw deformation, and/or failure.

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