Research Article Beneficial Effects of Concentrated Growth Factors and Resveratrol on Human Osteoblasts In Vitro Treated with Bisphosphonates Elisa Borsani , 1,2 Veronica Bonazza, 1 Barbara Buffoli , 1,2 Pier Francesco Nocini, 3 Massimo Albanese, 3 Francesca Zotti, 3 Francesco Inchingolo, 4 Rita Rezzani , 1,2 and Luigi F. Rodella 1,2 1 Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Brescia, Italy 2 Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs (ARTO)”, University of Brescia, Brescia, Italy 3 Department of Surgery, Dentistry, Pediatric and Gynecology, Division of Oral and Maxillofacial Surgery, University of Verona, Verona, Italy 4 Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Bari, Italy Correspondence should be addressed to Elisa Borsani; elisa.borsani@unibs.it Received 30 November 2017; Revised 19 February 2018; Accepted 5 April 2018; Published 16 May 2018 Academic Editor: Mirella Falconi Copyright © 2018 Elisa Borsani et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bisphosphonates are primary pharmacological agents against osteoclast-mediated bone loss and widely used in the clinical practice for prevention and treatment of a variety of skeletal conditions, such as low bone density and osteogenesis imperfecta, and pathologies, such as osteoporosis, malignancies metastatic to bone, Paget disease of bone, multiple myeloma, and hypercalcemia of malignancy. However, long-term bisphosphonate treatment is associated with pathologic conditions including osteonecrosis of the jaw, named BRONJ, which impaired bone regeneration process. Clinical management of BRONJ is controversy and one recent approach is the use of platelet concentrates, such as Concentrated Growth Factors, alone or together with biomaterials or antioxidants molecules, such as resveratrol. Te aim of the present study was to investigate the in vitro efects of Concentrated Growth Factors and/or resveratrol on the proliferation and diferentiation of human osteoblasts, treated or not with bisphosphonates. Human osteoblasts were stimulated for 3 days in complete medium and for 21 days in mineralization medium. At the end of the experimental period, the in vitro efect on osteoblast proliferation and diferentiation was evaluated using diferent techniques such as MTT, ELISA for the quantifcation/detection of osteoprotegerin and bone morphogenetic protein-2, immunohistochemistry for sirtuin 1 and collagen type I, and the Alizarin Red S staining for the rate of mineralization. Results obtained showed that Concentrated Growth Factors and/or resveratrol signifcantly increased osteoblast proliferation and diferentiation and that the cotreatment with Concentrated Growth Factors and resveratrol had a protective role on osteoblasts treated with bisphosphonates. In conclusion, these data suggest that this approach could be promised in the clinical management of BRONJ. 1. Introduction Bisphosphonates are primary pharmacological agents against osteoclast-mediated bone loss promoting the apoptosis of osteoclasts actively engaged in the degradation of mineral on the bone surface. Bisphosphonates, such as zoledronic acid or zoledronate, alendronate, and pamidronate, are important inhibitors of bone resorption and are widely used for manag- ing a variety of skeletal conditions characterized by increased osteoclast-mediated bone resorption, including multiple forms of osteoporosis (e.g., juvenile, postmenopausal, or se- nile), osteogenesis imperfecta, Paget disease of bone, hyper- calcemia, and malignancy metastatic to bone. However, long- term bisphosphonate treatment is associated with a rare but Hindawi BioMed Research International Volume 2018, Article ID 4597321, 13 pages https://doi.org/10.1155/2018/4597321