title: Osteonecrosis of the Jaw in Patients With Metastatic Renal Cell Cancer Treated With Bisphosphonates and Targeted Agents: Results of an Italian Multicenter Study and Review of the Literature.
abstract: Osteonecrosis of the jaw (ONJ) associated with the use of bisphosphonates has been rarely reported in metastatic renal cell cancer (RCC) patients. Since the introduction of combined therapies consisting of nitrogen-containing bisphosphonates (NBPs) and targeted agents, an increasing number of RCC patients were reported to develop ONJ, suggesting that therapeutic angiogenesis suppression might increase the risk of ONJ in NBPs users. We performed a multicenter retrospective study and reviewed literature data to assess the occurrence and to investigate the nature of ONJ in RCC patients taking NBPs and targeted agents. Nine Italian Centers contributed to the data collection. Patients with exposed and nonexposed ONJ were eligible for the study if they had been taking NBPs and were receiving targeted agents at the time of ONJ diagnosis. Forty-four RCC patients were studied. Patients were mostly male (82%), with a median age of 63 years (range, 45-85 years). Zoledronic acid (93%) and sunitinib (80%) were the most frequently used NBP and antiangiogenic agent, respectively. Other agents included Pamidronate, ibandronate, sorafenib, bevacizumab, mammalian target of rapamycin inhibitors. Forty-nine sites of ONJ were encountered, with the mandible being the preferred site of ONJ (52%); both jaws were affected in 5 cases (12%). The most common precipitating event was dental/periodontal infection (34%), followed by tooth extraction (30%). Oral triggers of ONJ were missing in 10 cases (23%). This unexpectedly high number of ONJ cases, in comparison with literature data, suggests that frequency of ONJ in RCC patients might be largely underestimated and suggests a potential role for targeted agents in the incremental risk of ONJ.
authors.affiliation: Medical Oncology Unit, Department of Oncology and Hematology, Ospedale SS Antonio e Biagio e C Arrigo Alessandria, Alessandria, Italy. Electronic address: vfusco@ospedale.al.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fusco
authors.affiliation: Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy; Italian Nephro-Oncology Group (Gruppo Italiano di Oncologia Nefrologica, G.I.O.N.), Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Unit of Maxillofacial Surgery, Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Saia
authors.affiliation: Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy; Italian Nephro-Oncology Group (Gruppo Italiano di Oncologia Nefrologica, G.I.O.N.), Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Paglino
authors.affiliation: Unit of Maxillofacial Surgery, Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Giordana
authors.initials: G
authors.lastname: Bettini
authors.affiliation: CTO, Azienda Ospedaliera Universitaria "Città della salute", Torino, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Scoletta
authors.affiliation: Department of Dentistry, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bonacina
authors.affiliation: Department of Otolaryngological/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Parma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vescovi
authors.affiliation: Department of Otolaryngological/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Parma, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Merigo
authors.affiliation: Medical Oncology, Santa Maria degli Angeli Hospital, Pordenone.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lo Re
authors.affiliation: Medical Oncology Unit, Department of Oncology and Hematology, Ospedale SS Antonio e Biagio e C Arrigo Alessandria, Alessandria, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Guglielmini
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Sector of Oral Medicine "V. Margiotta", University of Palermo, Palermo, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Di Fede
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Sector of Oral Medicine "V. Margiotta", University of Palermo, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Campisi
authors.affiliation: Unit of Maxillofacial Surgery, Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bedogni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D004164:Diphosphonates / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D007558:Italy; D007568:Jaw / Q000187:drug effects / Q000473:pathology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000139:chemically induced*; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D000077210:Sunitinib; D000077211:Zoledronic Acid
chemical_list: D020533:Angiogenesis Inhibitors; D004164:Diphosphonates; D007093:Imidazoles; D007211:Indoles; D011758:Pyrroles; D000077211:Zoledronic Acid; D000077210:Sunitinib
keywords: Bevacizumab; Sorafenib; Sunitinib; Zoledronic acid; m-TOR inhibitor