Abstract
Beginning with the first reports in 2001 and continuing to the present time, exposed bone in the jaws and, more recently, femoral fractures caused by the toxic effects of bisphosphonates on osteoclasts have become epidemic. In less than 10 years, more than 1,100 publications have been published on bisphosphonates-induced osteonecrosis of the jaw (BIONJ). 16 organizations have produced position papers, and tens of thousands of individuals have been afflicted by this serious drug-induced adverse side effect. The predictability of BIONJ occurring in humans has long been recognized, in the historical accounts of the phossy jaw epidemic between 1850 and 1906 and in the disease of osteopetrosis. BIONJ, as well as both of these pathologies, results from the over suppression of bone turnover (renewal), such that brittle and often necrotic bone develops in areas of the skeleton subject to the highest turnover in response to compressive forces and bending forces (e.g., alveolar bone in the jaws and the mid femur). The current challenge to clinicians is not to be ambivalent concerning the cause of BIONJ, as it is due to the bisphosphonate molecule itself, with all other medical conditions and drugs playing only contributing roles as co-morbidities. Accordingly, both the dose and the frequency of administration must be moderated. In addition, dental/oral and maxillofacial surgical teams must be able to competently manage and treat these individuals to control or resolve the disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Marx RE, Stern D (2002) Oral and maxillofacial pathology; a rational for diagnosis and treatment. Quintessence, Carol Stream
Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Surg 61:1567–1575
Ruggiero SL, Mehrota B, Rosenberg TJ et al (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527
Greenberg MS (2004) Intravenous bisphosphonates and osteonecrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 98:259–260
Migliorati CA, Schubert MM, Peterson DE, Seneda LM (2005) Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer 104:83–93
Durie BGM, Katz M, McCoy L, Crowley J (2004) Osteonecrosis of the jaws in myeloma: time dependent correlation with Aredia and Zometa use. Blood 104(1):216a
Durie BGM, Katz M, Crowley J (2005) Osteonecrosis of the jaws and bisphosphonates. N Engl J Med 353:99–100
Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 23(34):8580–8587
Hellstein C, Marek C (2005) Bisphosphonate osteonecrosis (bis-phossy jaw): is this phossy jaw of the 21st century? J Oral Maxillofac Surg 63:682–689
Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B (2009) American association of oral and maxillofacial surgeons position paper on bisphosphonate-related osteonecrosis of the jaws–2009 update. J Oral Maxillofac Surg 67(Suppl):2–12
Migliorati CA, Casiglia J, Epstein J, Jaclosen PL, Sioegel MA, Woo SB (2005) Managing the care of patients with bisphonate associated ostenecrosis: an American academy of oral medicine position paper. J Am Dent Assoc 136:1658–1668
Tarassoff P, Csermak K (2003) Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillfoac Surg 61:1238–1239
Hoff AO, Toth BB, Altunday K, Johnson MM, Warnecke CL et al (2008) Frequency an drisk factors associated with osteonecrosis of the jaw in cancer patient treated with intravenous bisphosphonates. J Bone Miner Res 23:826–836
Kilby JM, Saag MS (1997) The pathogenesis of HIV-1 infection. In: Powserly WG (ed) Manual of HIV therapeutics. Lippincot-Raven, Philadelphia, pp 1–6
Marx RE (2008) Uncovering the cause of “phossy jaw” Circa 1858 to 1906: oral and maxillofacial surgery closed case files–cased closed. J Oral Maxillofac Surg 66(11):2356–2363
Simon J (1863) FIFO Report of the medical officer of the privy council. HMSU, London
Campston JE (2010) Bisphosphonates and atypical femoral fractures: a time for reflection. Maturitas 65:3–4
Shane E (2010) Evolving data about subtrochanteric fractures and bisphoshonates. N Engl J Med 362:1761–1771
Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG (2008) Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma 22(5):346–350
Thorpe TE, Oliver T, Cunnigngham G (1899) Report on the use of phosphorus in manufacture of Lucifer mathches. HMSO, London
Miles AEW (1972) Phosphorus necrosis of the jaws: “phossy jaw”. Br Dent J 133:203–206
Hellenstein JW, Marek CL (2006) Bisphosphonate induced osteochemonecrosis of the jaws. An ounce of prevention may be worth a pound of cure. Spec Care Dent 26:8–12
Van Beek ER, Lowe CWGM, Papapoulos SE (2002) Bisphosphonates suppress bone resorption by a direct effect on early osteoclast precursors without affecting the osteoclastogenic capacity of osteogenic cells: the role of protein geranlyations in the action of nitrogen-containing bisphosphonates on osteoclast precursors. Bone 30:64
Rogers MJ, Gordon S, Benford HL et al (2000) Cellular and molecular mechanisms of action of bisphosphonates. Skeletal complications of malignancy. Cancer 88(Suppl):2961
Lasseter KC, Porras AG, Denker A et al (2005) Pharmacokinetic considerations in determining the terminal elimination half lives of bisphosphonates. Clin Drug Invest 25(2):107–114
Dixon RB, Trickler ND, Garetto LP (1997) Bone turnover in elderly canine mandible and tibia. J Dent Res 76:2579
Vignery A, Baron R (1980) Dynamic histomorphometry of alveolar bone remodeling in the adult rat. Anta Res 196:191–198
Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Horizon Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18):1809–1822
Aghaloo TL, Feinsenfeld AL, Pretetradis S (2010) Osteonecrosis of the jaws in a patient on denosumab. J Oral Maxillofac Surg 68:959–963
Gorlin RJ, Cohen MM, Henneham RCM (2001) Syndromes of the head and neck, 4th edn. Oxford University Press, New York, pp 285–289
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Milan
About this chapter
Cite this chapter
Marx, R.E. (2012). Introduction. In: De Ponte, F. (eds) Bisphosphonates and Osteonecrosis of the Jaw: A Multidisciplinary Approach. Springer, Milano. https://doi.org/10.1007/978-88-470-2083-2_1
Download citation
DOI: https://doi.org/10.1007/978-88-470-2083-2_1
Published:
Publisher Name: Springer, Milano
Print ISBN: 978-88-470-2082-5
Online ISBN: 978-88-470-2083-2
eBook Packages: MedicineMedicine (R0)