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Bisphosphonates associated with osteonecrosis of the jaw

Most of the cases of osteonecrosis of the jaw are seen in oncology patients that, besides intravenous bisphosphonates, have received chemotherapy in the long term for their base disease with or without intermittent cycles of steroids.

Mechanism of action begins to be recognized, the bisphosphonates are analogues of pyrophosphate and present high affinity to hidroxiapatita crystals and inhibit bone resorption. They inhibit osteoclastes activity too and therefore decrease bone remodelling.

Researchers at University Hospital, Madrid in Spain, have retrospectively analysed 15 cases of osteonecrosis of the jaw in patients treated with bisphosphonates.

Most of the study took place in oncology patients receiving antineoplasic therapy,often in addition to intermittent cycles of steroids.
A total of 10 women and 5 men were included in this report with an average age of 64 years. Both, multiple myeloma and breast cancer were the most common indication for bisphosphonate with 5 cases, followed by 3 cases for prostate cancer and 2 cases for osteoporosis.
Bisphosphonate administrated was Zoledronic acid ( Zometa ) in 13 cases, Alendronate ( Fosamax )oral route in 2 cases, and Pamidronate ( Aredia ) in addition to Zoledronic acid only in one case.

Tooth removal was found in 6 cases. The most common site of bone exposure was the mandible with 13 cases, 3 of them had involved the maxillary bone. Only 2 patients were affected in the maxillary bone exclusively; 14 patients presented with exposed bone in the oral cavity, the only patient that didn ’t, presented a gingival granuloma in the 48 and paresthesia in dental nerve territory.
Three patients presented with anesthesia, disesthesia, hipoesthesia or paresthesia; 3 cases of cutaneous fistula, 2 of oro-antral communication and maxillary sinusitis associated and 1 pathologic fracture of mandible were seen.

Biopsy was performed on 9 patients: the result was non specific inflammation in 3 cases and osteomyelitis in 6, in 5 of them Actinomyces could be detected.

A conservative attitude was supported for initial stage of treatment ( intermittent-continous cycles of systemic antibiotic therapy and mouth rinsing with Clorohexidine 0.12%, resulting successfully in 7 cases.
Besides exposed bone ulcerating soft tissues was remodelled in 5 cases. Among 2 patients with oro-antral communication and maxillary sinusitis associated: the first one presented a basal condition that advised cleaning of the maxillary sinus, bone contouring and covering the exposed bone with mucous flap; on the second one segmentary maxillectomy, extirpation of mucosa of the maxillary sinus, drainage, contouring bone and closure with mucous flap was performed without new exposed-bone appearance.

The only patient without exposed bone had a gingival granuloma in 48 and evolved satisfactorily after curettage, local debridement and closure with mucous flap.

In 2 cases with chronic suppuration and cutaneous fistula by osteonecrosis of jaw in the third quadrant, marginal mandibulectomy, preserving mandibular basal in the first one and contouring bone in the second one, followed by closure with mucous flap and fistulectomy in both of them was performed. The first one evolved successfully and the second one developed a pathologic fracture of mandible few months later, treated by radical resection of necrotic bone and elastic intermaxillary fixation in order to organize a bone reconstruction, in the short term.

Source: Medicina Oral Patologia Oral Y Cirugia Bucal, 2007