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Paolo Vescovi DDS, MScProfessore Associato di Clinica Odontostomatologica

Direttore EMDOLA (European Master Degreeon Oral Laser Applications)

Università degli Studi di Parma

OSTEONECROSIDELLA

MANDIBOLA

OSTEONECROSIS OF THE JAWS (ONJ)

BISPHOSPHONATE THERAPY (BPT)

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2003 2004 2005 2006 2007 2008 2009july

ONJ

ONJ ANDBisphosphonates

OsteonecrosisANDBisphosphonatesOsteonacrosis ofthe jaws ANDBisphosphonates

ONJ - BPT

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Osteonecrosis of thejaws

ONJ

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WIKIPEDIAwiki - vocabolo hawaiano = veloce

pedia - suffisso di enciclopedia

L’Espresso

VERO

Marzo 2008

Novembre 2007

sasalluteuteFebbraio 2008

Maggio 2008Radio Dee Radio Dee JayJay

…… ANCORA ANCORAMOLTI DUBBI MOLTI DUBBI ……??????????

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Non omogeneità di denominazione:

• osteochemonecrosis• bisphosphonate osteochemonecrosis of the jaws• “Bis-Phossy Jaw”• avascular osteonecrosis• bisphosphonate-induced osteopetrosis

• ONJ-BP (osteonecrosis of the jaws and bisphosphonate)• ONJ-BPT (osteonecrosis of the jaws –bisphosphonate

treatment related)• BON (bisphosphonate associated osteonecrosis)• BAJO (bisphosphonate associated jaw osteonecrosis)• BRON (bisphosphonate-related ostenecrosis)• BRONJ (bisphosphonate-related ostenecrosis of the jaw)• BONJ (bisphosphonate-associated osteonecrosis of the jaw )

?? OSTEONECROSI DELLA MANDIBOLA

110 PAZIENTI AFFETTI DA BRONJ: SEDIMANDIBOLARE 73 (66,4%) MASCELLARE 27 (24,5 %)

ESPERIENZA DELL’AMBULATORIO DI PATOLOGIA E CHIRURGIA ORALE

LASER ASSISTITADELL’ UNIVERSITA’ DI PARMAGennaio 2004 – Agosto 2009

CONTEMPORANEE 10 (9%)

OSTEONECROSI

DEI MASCELLARI

BRONJ

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BRONJ: Bisphosphonate-RelatedOsteonecrosis of the Jaws

PATOGENESI

STORIA

EPIDEMIOLOGIA

ASPETTI CLINICI

ASPETTI RADIOLOGICI

FATTORI DI RISCHIO

TERAPIA BRONJ

MULTIFACTORIALPATHOGENESIS

• A critical review of theliterature reveals thatthe etiology of ONJremains unknown and todate no direct causallink to bisphosphonateshas been established.

• Multifactorialpathogenesis

Silverman SL, Landesberg R: Osteonecrosis of the jaw and role of bisphosphonates: a criticalreview. The American Journal of Medicine 2009 Feb122(24):533-45

Migliorati CA, Siegel MA, Elting LS: Bisphosphonate-associated osteonecrosis: a long termcomplication of bisphosphonate treatment. Lancet Oncol 2006 June (7) 508-514

Migliorati CA: Lancet Oncol 2006;7:508-514

PATOGENESI

BONEREMODELLINGSUPRESSION

PATOGENESI

• In humans intracorticalremodelling rates of the jaw are10-20 times higher than insidethe cortex of the iliac creste

• Daily oral alendronatesignificantly suppressed theintracortical bone formation rateof the mandible in particular inthe alveolar region

Han ZH, Palmikar S, Rao DS et al: Effects of ethnicicy and age of menopause on the remodeling andturnover of the iliac bone: implications of mechanisms of bone loss. J Bone Mineral Res 1997;12:498

Allen MR, Burr DB: Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonatetreatment. J Oral Maxillofac Surg 2008;66:987

Allen MR. and Burr DB: J Oral Maxillfac Surg 67, 2009 suppl 1.

EFFECTS ON THE OSTEOCYTES

• BPs accumulate in theosteocyte lacunae

• Regions of non viablebone matrix : theosteocyte network filledwith minerals

• Most often observed inthe alveolar portion ofthe jaws

Allen MR, Burr DB: Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonatetreatment. J Oral Maxillofac Surg 2008;66:987

Allen MR. and Burr DB: J Oral Maxillfac Surg 67, 2009 suppl 1.

PATOGENESI

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ANGIOGENESIS SUPRESSION• Each bone remodelling unit

(Basic Multicellular Units:BMU)receives its nutrients throughvessels.

• Bone remodelling andangiogenesis are intimatelylinked

• Role of altered angiogenesisrelated to difficult woundhealing of soft tissues

• Disruption of clot andprovisional matrix formation inthe post extractive sockets

• Reduction of blood flow in themandible

Allen MR, Burr DB: The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so manyhypotheses, so few data. J Oral Maxillofac Surg 2009; suppl 1,67:61-70

PATOGENESI TOXIC EFFECTS ONTHE SOFT TISSUE

• BPs which accumulate in the bonehave direct toxic effects on the oralepithelium and inhibit normalhealing of soft tissue around thelesions caused by invasive dentalinterventions.

• BPs induces the death offibroblasts and epithelial cells bycombined intrinsic and extrinsicpathway of apoptosis

Reid IR, Bolland MJ: Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity?Bone 2007;41:318-320

Landesberg R, Cozin M, Cremers S, Woo V et val: Inhibition of oral mucosa cell wound healing bybisphosphonates. J Oral Maxillofac Surg 2008;66,839-847

Scheper MA, Badros A, Chaisuparat R et al: Effect of zoledronic acid on oral fibroblasts and epithelial cells:a potential mechanism of bisphosphonate-associated osteonecrosis. British Journal of Haematology2008, Nov;144:667-78

PATOGENESI

ROLE OF BACTERIALINFECTION

• Biofilm on thebone/tooth/mucosalsurfaces: Actinomyces

• Unclear if the infection is aprimary or secondaryevent in BRONJpathophysiology

Sedghizadeh PP, Kumar SK, Gorur A et al: Identification of microbial biofilms in osteonecrosis of the jawssecondary to bisphosphonate therapy. J Oral Maxillofac Surg 2008;66,767

PATOGENESI

Settembre20031° descrizione di ONJ-BPT

Marx RE: Pamidronate (aredia) and zoledronate (zometa) induced avascular necrosis of thejaws. A growing epidemic. J Oral Maxillofac Surg 2003,61:115-18

STORIA