Marcio A. de Oliveira Denise A. Asahi Celey A. E. Silveira Luiz Antonio P. A. Lima Michael Glick Marina Gallottini The effects of zoledronic acid and dexamethasone on osseointegration of endosseous implants: histological and histomorphometrical evaluation in rats Authors’ affiliations: Marcio A. de Oliveira, Denise A. Asahi, Luiz Antonio P. A. Lima, Marina Gallottini, Department of Stomatology, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil Celey A. E. Silveira, Department of Rheumatology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil Michael Glick, Department of Oral Medicine, Dental School of University at Buffalo, Buffalo, NY, USA Corresponding author: Marcio Augusto de Oliveira Department of Oral Pathology School of Dentistry, University of Sao Paulo Av. Prof. Lineu Prestes 2227 Cidade Universit aria – CEP 05508-000, S~ ao Paulo Brazil Tel.: +55 11 30911279 Fax: +55 11 30917894 e-mail: maocape@usp.br Key words: animal model, bisphosphonates, endosseous implants Abstract Background: Bisphosphonates are a widely used class of drugs that prevent bone loss. Several side effects related to bisphosphonate therapy have been reported, including osteonecrosis of the jaws associated with invasive dental procedures and implants placement. Objectives: To evaluate the influence of intravenous nitrogen-containing BPs in combination with or without dexamethasone on osseointegration of titanium implants placed in an animal model. Methods: Twenty-seven male Wistar rats were divided into three groups: group 1 was treated solely with zoledronic acid, group 2 was treated with zoledronic acid and dexamethasone, and group 3 did only receive saline solution injections. Two endosseous implants were placed in each tibia, and three animals from each group were sacrificed at postoperative times of seven, 14, and 28 days. Non-decalcified sections were observed with light microscopy for histological and histomorphometrical analyses. Results: Histomorphometrical analysis using the animals and the implants as unit of measurement revealed no statistically significant difference regarding bone-implant contact and bone density among the three groups. Histological observation revealed that zoledronic acid-treated animals in combination with or without dexamethasone showed expressive less bone remodeling activity at 14 and 28 days after implants placement, compared with control specimens. Conclusions: The studied bisphosphonate regimens did not interfere with the osseointegration of the implants, cortical, or medular bone deposition, but a possible lack of bone remodeling of the original cortical bone may affect long-term osseointegration. Bisphosphonates (BPs) are a class of drugs that prevent bone loss by inhibiting osteo- clast-mediated bone resorption, promoting osteoclast apoptosis, and impairing blood supply. There are two main types of BPs based on route of administration (oral vs. intravenous) and chemical composition (nitrogen vs. non-nitrogen containing). Oral BPs are used to treat osteopenia and osteopo- rosis, and intravenous (IV) nitrogen-contain- ing BPs are extensively used to prevent or delay cancer-related skeletal complications, such as new metastasis, pathological frac- tures, bone pain, and tumor growth, espe- cially associated with multiple myeloma, breast, and prostate carcinoma. (Durie et al. 2005; Favus 2010; Khosla et al. 2012) A range of anti-cancer protocols utilized a combina- tion regimen of zoledronic acid (ZA), an IV administered nitrogen-containing BP, antian- giogenic agents, and glucocorticoids to achieve a synergistic effect resulting in possi- ble enhanced apoptosis effect. (Bagan et al. 2006; Christodoulou et al. 2009) Several side effects related to BPs therapy have been reported, including fever, fatigue, flu-like symptoms, bone and muscle pain, stomach problems, anemia, and osteonecrosis of the jaws. Marx and Migliorati initially described osteonecrosis of the jaw in a group of individ- uals exposed to IV BPs, in 2003. (Marx 2003; Migliorati 2003) Since them letters, case reports, and case series of jaw osteonecrosis have been published in the oncology, dental, maxillofacial surgery, and general medical lit- erature. Despite that, there is a consensus that the benefits of BPs therapy, especially in malignant diseases, generally overshadow the risks. (Scully et al. 2006; Bagan et al. 2009; Ruggiero et al. 2009; Khosla et al. 2012). Date: Accepted 11 December 2013 To cite this article: de Oliveira MA, Asahi DA, Silveira CAE, Lima LAPA, Glick M, Gallottini M. The effects of zoledronic acid and dexamethasone on osseointegration of endosseous implants: histological and histomorphometrical evaluation in rats. Clin. Oral Impl. Res. 00, 2014, 1–5 doi: 10.1111/clr.12335 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1