CREATION OF AN EXPERIMENTAL “IN VITRO” BONE MODEL FOR THE STUDY AND DIAGNOSIS OF BISPHOSPHONATE-ASSOCIATED JAWBONE OSTEOMYELITIS.

Starting date
January 17, 2007
Duration (months)
12
Managers or local contacts
Bedogni Alberto , Nocini Pier Francesco
Keyword
'bisphosphonate', 'osteonecrosis', 'jaw'

The aim of the project is to establish an experimental “in vitro” bone model for the study and diagnosis of bisphosphonate-associated jawbone osteomyelitis, in order to:
1-determine the role of nitrogen-containing bisphosphonates in the pathogenesis of jawbone osteomyelitis;
2-identify the peculiar histomorphologic and histomorphometric features of disease, if any.

Methods:

1. quantitative analysis of the bone turnover and the anti-osteoclastic activity of amino-bisphosphonates by:

• Immunohistochemistry (Tunel method for apoptosis, Trap -tartrate resistant acid phosphatase- and ED1 staining), of serial samples of osteomyelitic bone, osteonecrotic bone and hystologically healthy bone obtained from patients suffering from amino-bisphosphonates jawbone osteomyelitis, who undergo surgical treatment.

• Histomorphometric: determination of the structure and micro-architecture of the bone previously exposed to amino-bisphosphonates from serial samples of osteomyelitic bone, osteonecrotic bone and hystologically healthy bone, obtained from patients suffering from amino-bisphosphonates jawbone osteomyelitis, who undergo surgical treatment.

2. quantitative analysis of the anti-angiogenic activity of amino-bisphosphonates by:
• Immunohistochemistry (anti VEGF-2 receptor antibodies) of serial samples of osteomyelitic bone, osteonecrotic bone and hystologically healthy bone, obtained from patients suffering from amino-bisphosphonates jawbone osteomyelitis, who undergo surgical treatment.

Expected results:
1. Amino-bisphosphonates do not cause gross metabolic modifications of the jawbone structure under normal conditions. Bone turnover is normal.
2. recruitment of mature osteoclasts occurs in the osteomyelitic bone, the majority of them being inactivated and apoptotic, whilst osteoclastic precursor cells being reduced. Bone remodeling is definitely inhibited.
3. Amino-bisphosphonates do not cause any angiogenetic modification of the jawbone structure under normal conditions.
4. Angiogenesis is altered in the osteomyelitic bone, in that the vessels are obliterated and congested. Neoangiogenesis is somehow reduced due to direct inhibition of vessels formation caused by amino-bisphosphonates.

Sponsors:

Novartis
Funds: assigned and managed by an external body

Project participants

Publications
Title Authors Year
Bisphosphonate-associated osteonecrosis can hide jaw metastases Bedogni A, Saia G, Ragazzo M, Bettini G, Capelli P, D'Alessandro E, Nocini PF, Russo LL, Lo Muzio L, Blandamura S. x
Long-term outcomes of surgical resection of the jaws in cancer patients with bisphosphonate-related osteonecrosis Bedogni, A.; Saia, G.; Bettini, G.; Tronchet, A.; Totola, A.; Bedogni, G.; Ferronato, G.; Nocini, PF.; Blandamura, S. 2011
Occurrence of bisphosphonate-related osteonecrosis of the jaw after surgical tooth extraction. Saia G.; Blandamura S.; Bettini G.; Tronchet A.; Totola A.; Bedogni G.; Ferronato G.; Nocini P.F.; Bedogni A. 2010
Oral bisphosphonate-associated osteonecrosis of the jaw following implant surgery: a case report and literature review. Bedogni A.; Bettini G.; Totola A.; Saia G.; Nocini P.F. 2010
Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology Bedogni A.; Blandamura S.; Lokmic Z.; Palumbo C.; Ragazzo M.; Ferrari F.; Tregnaghi A.; Pietrogrande F.; Procopio O.; Saia G.; Ferretti M.; Bedogni G.; Chiarini L.; Ferronato G.; Ninfo V.; Lo Russo L.; Lo Muzio L.; Nocini P.F. 2008
Mandible reconstruction in bisphosphonate-related osteonecrosis Ragazzo M.; Bettini G.; Saia G.; Chiarini L.; Ferronato G.; Bedogni A.; Nocini P.F. 2008
Prevenzione dell'osteonecrosi dei mascellari associata all'uso di bisfosfonati Bedogni A.; Nocini P.F. 2008
Surgical treatment of bisphosphonate-related osteonecrosis Bettini G.; Bedogni A.; Saia G.; Ragazzo M.; Ferronato G.; Nocini P.F. 2008
Tooth extraction in patients treated with bisphosphonates Saia G.; Bettini G.; Tronchet A.; Totola A.; Bedogni A.; Ferronato G.; Nocini P.F. 2008
A proposito di un caso di carcinoma squamoso della mandibola associato ad osteomielite in corso di trattamento con aminobisfosfonati Ragazzo M.; Saia G.; Bettini G.; Nocini P.F.; Bedogni A. 2007
Bisphosphonate-associated jawbone osteomyelitis: clinical, radiological and histological features Bedogni A.; Saia G.; Chiarini L.; Nocini P.F. 2007
Bisphosphonate-associated osteonecrosis can hide jaw metastases A. Bedogni; G. Saia; M. Ragazzo; G. Bettini; P. Capelli; E. D'Alessandro; PF. Nocini; L. Lo Russo; L. Lo Muzio ; S. Blandamura. 2007
Coesistenza di osteomielite cronica da bisfosfonati e metastasi di tumori solidi nei mascellari: presentazione di due casi clinici Bettini G.; Saia G.; Bissolotti G.; Nocini P.F.; Bedogni A. 2007
Valutazione a distanza dei risultati dell'applicazione di un protocollo estrattivo in pazienti in trattamento con aminobisfosfonati Saia G.; Bedogni A.; Bettini G.; Ragazzo M.; Nocini P.F. 2007
Valutazione dell'efficacia a distanza di un protocollo chirurgico demolitivo nel trattamento dell'osteonecrosi da bisfosfonati Nocini P. F.; Bettini G.; Bedogni A. 2007
Valutazione quali/quantitativa degli effetti degli amino-bisfosfonati sul turnover osseo e sulla neoangiogenesi nella malattia dei mascellari farmaco indotta Bedogni A.; Saia G.; Bettini G.; Chiarini L.; Nocini P.F. 2007

Activities

Research facilities