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Abstract
Introduction: Osteoporosis affects millions of elderly patients, and anti-resorptive
drugs (ARD) such as bisphosphonates (BP) represent the first-line therapy.
Despite the benefits related to the use of these medications, osteonecrosis of the
jaw is a significant complication in a subset of patients receiving these drugs.
Case presentation: This report documents a case of dramatic bisphosphonate-
related osteonecrosis associated with periodontitis and dental implant removal in
an osteoporotic patient treated with per os bisphosphonates for an uninterrupted
period of 15 years.
Key words: alendronate; implant; medication
Conclusion: The aim of this report was to discuss the administration period of related osteonecrosis of the jaw;
BP in the treatment of osteoporosis, the decision-making and clinical manage- osteonecrosis; osteoporosis; periodontitis
ment of severe MRONJ and the indications for dental implant placement in these
specific patients. Accepted for publication 14 October 2014
Bisphosphonates (BPs) have been osteoclasts, resulting in the disrup- resorptive agents (Black et al. 1996,
used since 1968 for the treatment of tion of bone turnover and the heal- Reginster et al. 2000, Kanis et al.
bone diseases such as bone metasta- ing process (Fleisch 1998, 2013).
ses, multiple myeloma, Pagets Magopoulos et al. 2007). Because of Despite the benefits of these
disease and calcium metabolism dis- their confirmed effectiveness in drugs, bisphosphonate-related osteo-
orders (osteoporosis) (Fleisch 1998). reducing osteoporosis-related bone necrosis of the jaw (BRONJ), a
After being deposited on the bone fractures, oral BPs such as ibandro- severe side effect of bisphosphonate
surface, BPs are internalized by oste- nate (Bonviva, Hoffmann, La therapy, was first described in the lit-
oclasts and induce the apoptosis of Roche, Basel, Switzerland), alendro- erature in 2003 (Marx 2003). Since
nate (Fosamax, Merck Sharp & this initial identification, many cases
Conflict of interest and source of Dhome, White House Station, NJ, have been reported, typically when
funding statement USA) and risedronate (Actonel, massive doses of BP were adminis-
Sanofi-Aventis, Paris, France) and tered intravenously, usually for on-
No external funding, apart from the intravenous BP, such as zoledronate cologic reasons (Dimitrakopoulos
support of the authors institution,
(Aclasta, Novartis, Basel, Switzer- et al. 2006). Recently, similar cases
was available for this case report. The
land), are considered first-line ther- of osteonecrosis of the jaw have
authors declare that they have no con-
flicts of interest in this case report.
apy in the treatment of osteoporosis been reported in patients treated
and are widely prescribed anti- with denosumab (DMab), a human
190 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Medication-Related Osteonecrosis of the jaws 191
experience, the patient, age, family or bone necrosis in patients receiv- incidence and risk factors. Journal of Clinical
Oncology 23, 85808587.
economic costs. ing this type of therapy. As the
Black, D. M., Bauer, D. C., Schwartz, A. V.,
Alveolar bone surgery represents ageing population grows, the Cummings, S. R. & Rosen, C. J. (2012)
one of the main risk factors for the number of patients with osteopo- Continuing bisphosphonate treatment for
development of MRONJ (Badros rosis increases, and the number osteoporosisfor whom and for how long?
et al. 2006). Madrid and Sanz of patients taking BPs for the New England Journal of Medicine 366, 2051
2053.
(Madrid & Sanz 2009) reviewed one treatment of osteoporosis is Black, D. M., Cummings, S. R., Karpf, D. B.,
prospective and three retrospective increasing. Prescribers of these Cauley, J. A., Thompson, D. E., Nevitt, M.
studies and reported that there were drugs should be aware that C., Bauer, D. C., Genant, H. K., Haskell, W.
no cases of MRONJ after implant potential consequences could L., Marcus, R., Ott, S. M., Torner, J. C.,
Quandt, S. A., Reiss, T. F. & Ensrud, K. E.
placements in 217 patients who took occur at any time during treat- (1996) Randomised trial of effect of alendro-
oral BPs for less than 5 years. They ment. nate on risk of fracture in women with exist-
concluded that oral BP administra- Not all bisphosphonates are the ing vertebral fractures. Fracture Intervention
Trial Research Group. Lancet 348, 1535
tion did not affect the short-term same, so recommendations for
1541.
implant success rate from 14 years. the discontinuation of bisphosph- Campisi, G., Fedele, S., Fusco, V., Pizzo, G., di
More recently, some studies showed onates need to be drug-specific, Fede, O. & Bedogni, A. (2014) Epidemiology,
that ligatures-induced periodontitis although recommendations about clinical manifestations, risk reduction and treat-
in rats can initiate MRONJ develop- monitoring after drug discontinu- ment strategies of jaw osteonecrosis in cancer
patients exposed to antiresorptive agents.
ment. The physiopathological bone ation and reinitiating anti-frac-
Future Oncology 10, 257275.
remodelling related to periodontitis ture therapy await further Dimitrakopoulos, I., Magopoulos, C. & Karakasis,
would not occur because of the lack studies. D. (2006) Bisphosphonate-induced avascular
of osteoclast activity and the peri- Despite the low risk of MRONJ osteonecrosis of the jaws: a clinical report of 11
cases. International Journal of Oral and Maxil-
odonthopathogens would directly in oral BPs users, role of active
lofacial Surgery 35, 588593.
colonize the necrotic bone (Kang periodontitis and the fate of den- Dimopoulos, M. A., Kastritis, E., Bamia, C.,
et al. 2013). In this case, the origin tal implants in these patients Melakopoulos, I., Gika, D., Roussou, M.,
of the MRONJ process is question- remain uncertain. Patients at risk Migkou, M., Eleftherakis-Papaiakovou, E.,
able. It is difficult to determine should be given a full explana- Christoulas, D., Terpos, E. & Bamias, A.
(2009) Reduction of osteonecrosis of the jaw
whether the periodontitis on teeth tion of the potential risks of (ONJ) after implementation of preventive mea-
36/peri-implantitis or implant implant failure and BRONJ sures in patients with multiple myeloma treated
removal or a combination of both development. with zoledronic acid. Annals of Oncology 20,
triggered the MRONJ. In the peri- 117120.
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apical radiograph performed before phosphonate osteonecrosis of the jaws: is there
implant removal (Fig. 2) displays a role for resection and vascularized recon-
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L. A., Melakopoulos, I., Bozas, G., Madrid, C. & Sanz, M. (2009) What impact do
This report serves to alert den- Koutsoukou, V., Gika, D., Anagnostopoulos,
A., Papadimitriou, C., Terpos, E. & Dimopou-
systemically administrated bisphosphonates
have on oral implant therapy? A systematic
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2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Medication-Related Osteonecrosis of the jaws 195
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2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd