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Azienda Ospedaliera Nazionale“SS. Antonio e Biagio e Cesare Arrigo”Working Paper of Public Healthnr. 12/20122001-2006 largely treated with BPs in public and private centres, on a monthly basis,accordingly to less recent guidelines indicating continuous BP treatment “until evidence ofsubstantial decline in a patient's general performance status” [138-140] . Secondly, on thecontrary, the SSN did not adopt adequate coverage for oral health measures, that are mainlyleft to individual choice and are mostly under care of private dentists; direct and indirectmeasures indicate an insufficient median status of oral health in Italian people, especially ofmiddle-age and elderly people (the age in which you can find most of cancer and myelomapatients). Consequently, the sum of systemic factors (large amounts of iv monthly BPs, forprolonged time, particularly of zoledronic acid) and of local factors (bad oral health status;periodontal disease; high number of teeth needed to be extracted without specific protocolduring BP treatment; etc) could explain such a high number of BRONJ cases in years 2004-2008.In Italy diffusion of knowledge of BRONJ among specialists and medical and dentistpractitioners was late in comparison with North America. In USA, since 2004 NovartisPharmaceuticals Inc , the major manufacturer of large-diffused iv bisphosphonates,pamidronate ( Aredia ) and zoledronic acid (Zometa) alerted involved specialists(oncologists, haematologists, dentists, maxillofacial surgeons) with a “white paper” drawn upin March 2004 and made public in June 2004, followed by a “dear doctor” letter (September2004); patients were even alerted through meetings with patient advocacy groups since May2004 and the diffusion of a patient information booklet [4]. In Italy , only on late 2005 and on2006, after stimulation [141] and after first publications on main international medicinejournals [142], BP manufacturers and health authorities adopted measures to inform involvedspecialists. Afterwards, especially since 2007, information about this “new disease” wasdiffused, also among dentist practitioners. However, also in Italy [143] as well as in othercountries [144-145] patients ignorance about administered BP treatment , as well as dentistsand physicians insufficient information, remains a substantial risk factor for inducing newcases of BRONJ .On the other side, the reduction of number of new BRONJ cases in latest years in some largeItalian referral centers (data not yet published) as well in one regional area [60] seemindicate encouraging results from adoption of preventive measures, together with a moreselective use of BPs (as indicated by more recent guidelines) [146-147] .In conclusion: experience of Italian patients suffering from ONJ, together with work ofItalian dentists, physicians and researchers, appears of paramount importance in order to8
Azienda Ospedaliera Nazionale“SS. Antonio e Biagio e Cesare Arrigo”Working Paper of Public Healthnr. 12/2012study ONJ and minimize as much as possible this severe side-effect of efficacious medicaltreatments.References[1] R.E. Marx, “Pamidronate (Aredia) and Zolendronate (Zometa) induced avascular necrosisof the jaws: a growing epidemic,” J Oral Maxillofac Surg., vol. 61, pp. 1115-1118, 2003.[2] S.L. Ruggiero, J. R. Tracey, S.L. Engroff “Osteonecrosis of the Jaws Associated With theUse of Bisphosphonates: A Review of 63 Cases,” J Oral Maxillofac Surg., vol.62 pp.527-534, 2004.1. [3]C.A. Migliorati “Bisphosphonates and oral cavity avascular bone necrosis”. J ClinOncol. Vol. 21(22): pp 4253-4, 2004.2. [4] S.L. Ruggiero , “Bisphosphonate-related osteonecrosis of the jaw (BRONJ): initialdiscovery and subsequent development” J Oral Maxillofac Surg., Vol. 67 (suppl 5),pp.13-18, 2009.3. [5] M.R. Allen, D.B. Burr,“ The Pathogenesis of Bisphosphonate-Related Osteonecrosisof the Jaw: So Many Hypotheses, So Few Data,” J Oral Maxillofac Surg., vol. 67, pp.61-70, 2009.[6] C.A. Migliorati, J.B. Epstein, E. Abt, J.R. Berenson, “Bisphosphonate-associatedosteonecrosis (BON) is a complication,” Nat. Rev. Endocrinol., vol. 7, pp. 34-42, 2011.[7] C.L. Estilo, M. Fornier, A. Farooki, D. Carlson, G. Bohle III, J.M. Huryn, “Osteonecrosisof the Jaw Related to Bevacizumab,” Journal of Clinical Oncology, vol. 26, no. 24, pp.4037-4043, 2008.[8] J. Ayllon, V. Launay-Vacher, J. Medioni, C. Cros, J. P. Spano, S. Oudard, “Osteonecrosisof the jaw under bisphosphonate and antiangiogenic therapies: cumulative toxicityprofile?”Annals of Oncology 20(3): pp 600-1, 2009.[9] T. L. Aghaloo, A. L. Felsenfeld, S. Tetradis, “Osteonecrosis of the Jaw in a Patient onDenosumab,” J Oral Maxillofac Surg., 68(5): pp 959-63, 2010.[10] V. Fusco, C. Galassi, A. Berruti, L. Ciuffreda, C. Ortega, G. Ciccone, A. Angeli, O.Bertetto, “Osteonecrosis of the jaw after zoledronic acid and denosumab treatment,” J ClinOncol., vol. 29, no. 17, pp. 521-522, 2011.[11] F. Bertoldo, D. Santini, V. Lo Cascio, “Bisphosphonates and osteomyelitis of the jaw: apathogenic puzzle,” Nat Clin Pract Oncol., vol. 4, no. 12, pp. 711-721, 2007.9
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