Bisphosphonate-associated osteonecrosis can hide jaw metastases Alberto Bedogni a , Giorgia Saia b , Mirko Ragazzo b , Giordana Bettini a , Paola Capelli c , Emiliano D'Alessandro d , Pier Francesco Nocini a , Lucio Lo Russo e , Lorenzo Lo Muzio e, ⁎ , Stella Blandamura d a Section of Oral and Maxillofacial Surgery, University of Verona, Verona, Italy b Unit of Maxillofacial Surgery, University of Padova, Padova, Italy c Institute of Pathology, University of Verona, Verona, Italy d Section of Pathological Anatomy, University of Padova, Padova, Italy e Department of Surgical Sciences, University of Foggia, V.le Pinto, 71100 Foggia, Italy Received 5 April 2007; revised 2 August 2007; accepted 7 August 2007 Available online 29 August 2007 Abstract Background: Osteonecrosis of the jaw is a well known potential complication of bisphosphonate treatment but its pathogenesis is poorly understood. The current management of patients with bisphosphonate-associated osteonecrosis (BON) is based on “expert recommendations” and there is a recognized need of better evidence. We report two cases where BON hid jaw metastases and use them to discuss some limitations of the current recommendations. Patients: Two patients undergoing long-term I.V. amino-bisphosphonate treatment for metastatic cancer presented with areas of intraorally exposed jawbone. Bisphosphonate-associated osteonecrosis was diagnosed on the basis of medical history, clinical and radiological features. They underwent surgical resection of the affected jaw due to unrelenting pain and lack of response to conservative treatments. Results: Histological examination of the surgical specimen revealed cancer cells at the margins of the site of osteonecrosis. Our patients did not undergo bone biopsy according to current recommendations, due to lack of clinical and radiological signs suggestive of jaw metastases. Conclusions: Our findings show that: i) patients with BON may also have jaw metastases; ii) there may not be clinical or imaging hints to this fact and; iii) that a biopsy based on careful selection of the site (with inclusion of necrotic margins) may be needed to reach the correct diagnosis. Further studies should be performed on this topic because of its very important prognostic implications. © 2007 Elsevier Inc. All rights reserved. Keywords: Bisphosphonate; Osteonecrosis; Metastasis; Jawbone; Osteomyelitis Introduction Bisphosphonates play a central role in the management of malignancy-associated hypercalcemia and the prevention of bone complications in patients with bone metastases or multiple myeloma. Bisphosphonates bind selectively to hydroxyapatite and accumulate in sites of bone remodeling where they inhibit osteoclastic activity. They also have anti-angiogenic properties both in vitro and in vivo [1]. Osteonecrosis of the jaw is a well known potential com- plication of bisphosphonate treatment but its pathogenesis is poorly understood [2–7]. The current management of patients with bisphosphonate-associated osteonecrosis (BON) is based on “expert opinions”, but there is a recognized need of better evidence [8–10]. We report two cases where BON hid jaw metastases and use them to discuss some limitations of the current recommendations. Cases presentation Clinical case 1 A 65-year-old woman with metastatic breast carcinoma had been treated from 2004 with tamoxifene, steroids and monthly I. V. infusion of zoledronate, with good control of pain and an acceptable quality of life. Bone 41 (2007) 942 – 945 www.elsevier.com/locate/bone ⁎ Corresponding author. Fax: +39 0881 685809. E-mail address: llomuzio@tin.it (L. Lo Muzio). 8756-3282/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.bone.2007.08.025