OBJECTIVES: The aim was to evaluate the effect of three nitrogen-containing bisphosphonates at different concentrations on osteoblast growth, differentiation, and antigenic profile, using the MG-63 cell line as osteoblast model, in order to determine the role of osteoblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIALS AND METHODS: Osteoblasts were incubated in culture medium with 10(-5), 10(-7), or 10(-9) M of pamidronate, alendronate, or ibandronate. Proliferative capacity of the osteoblasts was determined by spectrophotometry (MTT) at 24 and 48 h of culture. Flow cytometry was used to study antigenic profile (CD54, CD80, CD86, HLA-DR) and phagocytic activity. Cell differentiation was evaluated at 7, 15, and 21 days by the study of nodule formation and alkaline phosphatase activity (ALP) at 24 h by spectrophotometric assay. RESULTS: Pamidronate, alendronate, and ibandronate each exerted a significant stimulatory effect on MG63 proliferation that depended on the dose and treatment duration (p < 0.05). In general, a significantly decreased expression of CD54, CD80, and HLA-DR membrane antigens was observed after 24 h of treatment with each nitrogen-containing bisphosphonate (p < 0.05), but there was no significant difference in phagocytic activity versus controls. A decrease in ALP activity was observed after 24 h of treatment and a decrease in calcium deposition after 15 and 21 days (p < 0.05). CONCLUSION: Nitrogen-containing bisphosphonates can increase the proliferation of MG-63 osteoblast-like cells, modulate their expression of co-stimulatory molecules associated with immune function, and decrease their differentiation capacity, generally at low doses. CLINICAL RELEVANCE: These findings suggest that low doses of nitrogen-containing bisphosphonates exert their effect on osteoblasts by altering their physiology, which would explain the disruption of their repair capacity and may be directly related to the development of BRONJ.
OBJECTIVES: The aim was to evaluate the effect of three nitrogen-containing bisphosphonates at different concentrations on osteoblast growth, differentiation, and antigenic profile, using the MG-63 cell line as osteoblast model, in order to determine the role of osteoblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIALS AND METHODS: Osteoblasts were incubated in culture medium with 10(-5), 10(-7), or 10(-9) M of pamidronate, alendronate, or ibandronate. Proliferative capacity of the osteoblasts was determined by spectrophotometry (MTT) at 24 and 48 h of culture. Flow cytometry was used to study antigenic profile (CD54, CD80, CD86, HLA-DR) and phagocytic activity. Cell differentiation was evaluated at 7, 15, and 21 days by the study of nodule formation and alkaline phosphatase activity (ALP) at 24 h by spectrophotometric assay. RESULTS:Pamidronate, alendronate, and ibandronate each exerted a significant stimulatory effect on MG63 proliferation that depended on the dose and treatment duration (p < 0.05). In general, a significantly decreased expression of CD54, CD80, and HLA-DR membrane antigens was observed after 24 h of treatment with each nitrogen-containing bisphosphonate (p < 0.05), but there was no significant difference in phagocytic activity versus controls. A decrease in ALP activity was observed after 24 h of treatment and a decrease in calcium deposition after 15 and 21 days (p < 0.05). CONCLUSION:Nitrogen-containing bisphosphonates can increase the proliferation of MG-63 osteoblast-like cells, modulate their expression of co-stimulatory molecules associated with immune function, and decrease their differentiation capacity, generally at low doses. CLINICAL RELEVANCE: These findings suggest that low doses of nitrogen-containing bisphosphonates exert their effect on osteoblasts by altering their physiology, which would explain the disruption of their repair capacity and may be directly related to the development of BRONJ.
Authors: J M Lane; S N Khan; W J O'Connor; M Nydick; J P Hommen; R Schneider; E Tomin; J Brand; J Curtin Journal: Clin Orthop Relat Res Date: 2001-01 Impact factor: 4.176
Authors: Francisco Javier Manzano-Moreno; Javier Ramos-Torrecillas; Elvira de Luna-Bertos; Rebeca Illescas-Montes; Timothy R Arnett; Concepción Ruiz; Olga García-Martínez Journal: Clin Oral Investig Date: 2018-06-06 Impact factor: 3.573
Authors: Francisco Javier Manzano-Moreno; Javier Ramos-Torrecillas; Lucia Melguizo-Rodríguez; Rebeca Illescas-Montes; Concepción Ruiz; Olga García-Martínez Journal: Int J Med Sci Date: 2018-02-12 Impact factor: 3.738
Authors: Francisco Javier Manzano-Moreno; Rebeca Illescas-Montes; Lucia Melguizo-Rodriguez; Victor J Costela-Ruiz; Olga García-Martínez; Concepción Ruiz; Javier Ramos-Torrecillas Journal: Int J Med Sci Date: 2019-10-21 Impact factor: 3.738