Abstract
INTRODUCTION: Patients treated with nitrogen-containing bisphosphonates, such as zoledronic acid (ZA), have frequently shown oral bone exposure areas, termed osteonecrosis. In addition, these patients may also present low repair and regeneration potential, mainly after tooth extractions. These side-effects caused by bisphosphonates may be due to their inhibitory effects on oral mucosa and local bone cells. OBJECTIVE: To evaluate the effects of ZA on the mineralization capacity of cultured osteoblasts. MATERIALS AND METHODS: Human immortalized osteoblasts (SaOs-2) were grown in plain culture medium (Dulbecco's Modified Eagle Medium [DMEM] + 10% fetal bovine serum [FBS]) in wells of 24-well plates. After 48-hour incubation, the plain DMEM was replaced by a solution with ZA at 5 µM which was maintained in contact with cells for seven, 14 or 21 days. After these periods, cells were evaluated regarding alkaline phosphatase (ALP) activity and mineral nodule formation (alizarin red). Data were statistically analyzed by Mann-Whitney test, at 5% of significance level. RESULTS: ZA caused significant reduction on ALP activity and mineral nodules formation by cultured osteoblasts in all evaluated periods (p < 0.05). CONCLUSION: These data indicate that ZA causes inhibition on the osteogenic phenotype of cultured human osteoblasts, which, in turn, may reduce bone repair in patients subjected to ZA therapy.
Highlights
Patients treated with nitrogen-containing bisphosphonates, such as zoledronic acid (ZA), have frequently shown oral bone exposure areas, termed osteonecrosis
Bisphosphonates are indicated for the treatment of diseases characterized by intense bone resorption. Their main mechanism of action is inhibition of osteoclast maturation and activity. The use of these drugs has been linked to the development of osteonecrosis in the oral cavity, a condition that seems to be associated with the reduction of tissue repair capacity[2, 3]
Several studies demonstrate that bisphosphonates present inhibitory effect on different cell types, like osteoblast and epithelial cells, what may explain, at least partially, the development of osteonecrosis[1, 11, 14]
Summary
Patients treated with nitrogen-containing bisphosphonates, such as zoledronic acid (ZA), have frequently shown oral bone exposure areas, termed osteonecrosis These patients may present low repair and regeneration potential, mainly after tooth extractions. After 48-hour incubation, the plain DMEM was replaced by a solution with ZA at 5 μM which was maintained in contact with cells for seven, 14 or 21 days After these periods, cells were evaluated regarding alkaline phosphatase (ALP) activity and mineral nodule formation (alizarin red). The zoledronic acid (ZA) is known as a potent bisphosphonate, due to its greater capacity of adherence to the bone tissue[9] It is administered intravenously, with the frequency of use varying according to the disease to be treated and the established therapy[9]. Patients in treatment with this kind of bisphosphonate have presented higher risk for the development of osteonecrosis, what is directly related to the dose and the frequency of use[9]
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