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Bisphosphonate induced osteonecrosis of the mandible
European Journal of Radiology Extra 66 (2008) e9–e11
Bisphosphonate induced osteonecrosis of the mandible Rathan M. Subramaniam, Gary M. Miller ∗ Division of Neuroradiology, Department of Radiology, Mayo Clinic and Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, United States Received 30 December 2007; accepted 14 January 2008
Abstract Bisphosphonate-associated osteonecrosis of the mandible has been recently described. Since the diagnosis is confirmed by imaging rather than biopsy and treatment response is monitored by imaging, radiologists need to know this new entity. We present a case of a 64-year-old female patient who was on chronic bisphosphonate therapy for osteoporosis developed osteonecrosis of the mandible which was confirmed by multi-detector CT and review the updated literature for radiologists. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Madibular osteonecrosis; Bisphosphonate; MDCT
1. Introduction Bisphosphonate-associated osteonecrosis of the jaw has been recently described [1,2]. With increasing use of bisphosphonates, this complication is now being encountered more frequently. Diagnosis of bisphosphonate-associated osteonecrosis is clinical as biopsy is avoided in these patients [2]. Imaging plays an important role in the diagnosis and assessing therapy response. Bisphosphonates are synthetic analogues of pyrophosphate used for the treatment of hypercalcemia in patients with malignancies and bone metastasis and for the treatment of many other disorders such as metabolic bone diseases, Paget’s disease, and osteoporosis. The pharmacological activity is related to the inhibition of the osteoclastic function which leads to resorption and reduction of bone vascularization. We present a case of a 64year-old patient who received chronic bisphosphonate therapy for osteoporosis presenting with osteonecrosis of the mandible. Radiologists need to be aware of this entity to recognize and initiate early diagnosis and appropriate management. 2. Case report The patient was a 64-year-old female who has been on Fosamax for seven years for osteoporosis. About a month ago she ∗
Corresponding author. Tel.: +1 507 284 8550; fax: +1 507 266 4609. E-mail address: [email protected] (G.M. Miller).
1571-4675/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2008.01.009
developed pain in the left anterior mandible. A provisional diagnosis of osteonecrosis was rendered by the local oral surgeon. The patient was prescribed chlorhexidine rinses twice a day and pain medications. She sought a second opinion for possible mandibular necrosis at our institution. On physical examination, there was a bony protuberance in the right anterior mandible at the junction of loose and attached mucosa which was red. There was no purulent discharge. The CT scan demonstrated sclerosis, moth eaten appearance of inferior aspect of the right anterior mandible. There was erosion of the lingual cortex and small bony fragments (Fig. 1) consistent with osteonecrosis. Patient was treated conservatively with antibiotics (clindamycin) for two weeks and chlorhexidine rinses indefinitely. Patients symptoms improved and to be followed up at six months with repeat CT study. 3. Discussion Osteonecrosis of the mandible has multiple etiologies and is most commonly seen following radiation therapy for the head and neck malignancies [3]. Bisphosphonate use and the development of mandibular osteonecrosis have been well established [4]. The changes in bone metabolism associated with surgical treatment and implant trauma seem to be key factors in the development of osteonecrosis. The presentations simulate dental abscesses, “tooth aches,” denture sore spots, and osteomyelitis. A tooth extraction is the most common trigger [5], even though
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R.M. Subramaniam, G.M. Miller / European Journal of Radiology Extra 66 (2008) e9–e11
Fig. 1. (a) Axial and (b) coronal CT demonstrate sclerosis, moth eaten appearance of inferior aspect of the right anterior mandible. There was erosion of the lingual cortex and small bony fragment (c) consistent with osteonecrosis.
there have been cases of lesions arising spontaneously in areas not subjected to dental extractions. The most commonly reported sites of jaw osteonecrosis are the upper jaw in 38–80.5% of cases, the lower jaw in 14–63% and both jaws in 5.5–23% [6]. No other sites of osteonecrosis associated with the use of bisphosphonates have been reported in the literature. The exact mechanism of bisphosphonate induced osteonecrosis of the jaws is unclear. A proposed mechanism for involvement of the alveolar ridge along the mandible or maxilla includes the presence of teeth, leading to potential environmental bone exposure which requires an increase in bone turnover because of repeated inflammation, abscess formation, and tooth extraction. Edentulous patients often have poor fitting dentures which may lead to chronic irritation and inflammation to the gingiva and underlying alveolar bone. Inhibition of osteoclast function prevents bone turnover at these sites of inflammation, potentially leading to a sequestered area of osteomyelitis and
eventually osteonecrosis. Bisphosphonates also have an antiangiogenic effect [7], which could potentiate the ischemic effects. These effects may be cumulative in nature, with minimal trauma resulting in a nonhealing site of bone and eventual osteonecrosis. The most common imaging finding in osteonecrosis of the jaws is osseous sclerosis. This can vary from subtle thickening of the lamina dura and alveolar crest to attenuated osteopetrosislike sclerosis. Other findings such as osteolysis, soft tissue swelling, periosteal new bone formation, periapical lucencies, oroantral fistula, and sequestra, which are likely to correspond with the presence of infection [2]. The imaging differential diagnosis includes chronic sclerosing osteomyelitis of the jaws, osteonecrosis secondary to irradiation, metastasis, and Paget’s disease. In established cases of osteonecrosis of jaw, the primary goal of treatment is to control the osteomyelitis. Control and limitation of progression has been obtained in most cases with
R.M. Subramaniam, G.M. Miller / European Journal of Radiology Extra 66 (2008) e9–e11
long term or intermittent courses of penicillin-type antibiotics, chlorhexidine mouth wash and periodic minor debridement of soft-textured sequestrating bone and wound irrigation. As more and more imaging studies are conducted for many of these patients for diagnosis and follow up, the radiologist should be aware of this entity. References [1] Sanna G, Zampino MG, Pelosi G, Nole F, Goldhirsch A. Jaw avascular bone necrosis associated with long-term use of biphosphonates. Ann Oncol 2005;16:1207–8. [2] Phal PM, Myall RWT, Assael LA, Weissman JL. Imaging findings of bisphosphonate-associated osteonecrosis of the jaws. AJNR Am J Neuroradiol 2007;28:1139–45.
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[3] Marx R. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115–7. [4] Marx R, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567– 75. [5] Migliorati CA. Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol 2003;21:4253–4. [6] Migliorati C, Schubert M, Peterson D. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone. Cancer 2005;104:83– 93. [7] Wood J, Bonjean K, Ruetz S, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002;302:1055–61.
Bisphosphonate induced osteonecrosis of the mandible Rathan M. Subramaniam, Gary M. Miller ∗ Division of Neuroradiology, Department of Radiology, Mayo Clinic and Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, United States Received 30 December 2007; accepted 14 January 2008
Abstract Bisphosphonate-associated osteonecrosis of the mandible has been recently described. Since the diagnosis is confirmed by imaging rather than biopsy and treatment response is monitored by imaging, radiologists need to know this new entity. We present a case of a 64-year-old female patient who was on chronic bisphosphonate therapy for osteoporosis developed osteonecrosis of the mandible which was confirmed by multi-detector CT and review the updated literature for radiologists. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Madibular osteonecrosis; Bisphosphonate; MDCT
1. Introduction Bisphosphonate-associated osteonecrosis of the jaw has been recently described [1,2]. With increasing use of bisphosphonates, this complication is now being encountered more frequently. Diagnosis of bisphosphonate-associated osteonecrosis is clinical as biopsy is avoided in these patients [2]. Imaging plays an important role in the diagnosis and assessing therapy response. Bisphosphonates are synthetic analogues of pyrophosphate used for the treatment of hypercalcemia in patients with malignancies and bone metastasis and for the treatment of many other disorders such as metabolic bone diseases, Paget’s disease, and osteoporosis. The pharmacological activity is related to the inhibition of the osteoclastic function which leads to resorption and reduction of bone vascularization. We present a case of a 64year-old patient who received chronic bisphosphonate therapy for osteoporosis presenting with osteonecrosis of the mandible. Radiologists need to be aware of this entity to recognize and initiate early diagnosis and appropriate management. 2. Case report The patient was a 64-year-old female who has been on Fosamax for seven years for osteoporosis. About a month ago she ∗
Corresponding author. Tel.: +1 507 284 8550; fax: +1 507 266 4609. E-mail address: [email protected] (G.M. Miller).
1571-4675/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2008.01.009
developed pain in the left anterior mandible. A provisional diagnosis of osteonecrosis was rendered by the local oral surgeon. The patient was prescribed chlorhexidine rinses twice a day and pain medications. She sought a second opinion for possible mandibular necrosis at our institution. On physical examination, there was a bony protuberance in the right anterior mandible at the junction of loose and attached mucosa which was red. There was no purulent discharge. The CT scan demonstrated sclerosis, moth eaten appearance of inferior aspect of the right anterior mandible. There was erosion of the lingual cortex and small bony fragments (Fig. 1) consistent with osteonecrosis. Patient was treated conservatively with antibiotics (clindamycin) for two weeks and chlorhexidine rinses indefinitely. Patients symptoms improved and to be followed up at six months with repeat CT study. 3. Discussion Osteonecrosis of the mandible has multiple etiologies and is most commonly seen following radiation therapy for the head and neck malignancies [3]. Bisphosphonate use and the development of mandibular osteonecrosis have been well established [4]. The changes in bone metabolism associated with surgical treatment and implant trauma seem to be key factors in the development of osteonecrosis. The presentations simulate dental abscesses, “tooth aches,” denture sore spots, and osteomyelitis. A tooth extraction is the most common trigger [5], even though
e10
R.M. Subramaniam, G.M. Miller / European Journal of Radiology Extra 66 (2008) e9–e11
Fig. 1. (a) Axial and (b) coronal CT demonstrate sclerosis, moth eaten appearance of inferior aspect of the right anterior mandible. There was erosion of the lingual cortex and small bony fragment (c) consistent with osteonecrosis.
there have been cases of lesions arising spontaneously in areas not subjected to dental extractions. The most commonly reported sites of jaw osteonecrosis are the upper jaw in 38–80.5% of cases, the lower jaw in 14–63% and both jaws in 5.5–23% [6]. No other sites of osteonecrosis associated with the use of bisphosphonates have been reported in the literature. The exact mechanism of bisphosphonate induced osteonecrosis of the jaws is unclear. A proposed mechanism for involvement of the alveolar ridge along the mandible or maxilla includes the presence of teeth, leading to potential environmental bone exposure which requires an increase in bone turnover because of repeated inflammation, abscess formation, and tooth extraction. Edentulous patients often have poor fitting dentures which may lead to chronic irritation and inflammation to the gingiva and underlying alveolar bone. Inhibition of osteoclast function prevents bone turnover at these sites of inflammation, potentially leading to a sequestered area of osteomyelitis and
eventually osteonecrosis. Bisphosphonates also have an antiangiogenic effect [7], which could potentiate the ischemic effects. These effects may be cumulative in nature, with minimal trauma resulting in a nonhealing site of bone and eventual osteonecrosis. The most common imaging finding in osteonecrosis of the jaws is osseous sclerosis. This can vary from subtle thickening of the lamina dura and alveolar crest to attenuated osteopetrosislike sclerosis. Other findings such as osteolysis, soft tissue swelling, periosteal new bone formation, periapical lucencies, oroantral fistula, and sequestra, which are likely to correspond with the presence of infection [2]. The imaging differential diagnosis includes chronic sclerosing osteomyelitis of the jaws, osteonecrosis secondary to irradiation, metastasis, and Paget’s disease. In established cases of osteonecrosis of jaw, the primary goal of treatment is to control the osteomyelitis. Control and limitation of progression has been obtained in most cases with
R.M. Subramaniam, G.M. Miller / European Journal of Radiology Extra 66 (2008) e9–e11
long term or intermittent courses of penicillin-type antibiotics, chlorhexidine mouth wash and periodic minor debridement of soft-textured sequestrating bone and wound irrigation. As more and more imaging studies are conducted for many of these patients for diagnosis and follow up, the radiologist should be aware of this entity. References [1] Sanna G, Zampino MG, Pelosi G, Nole F, Goldhirsch A. Jaw avascular bone necrosis associated with long-term use of biphosphonates. Ann Oncol 2005;16:1207–8. [2] Phal PM, Myall RWT, Assael LA, Weissman JL. Imaging findings of bisphosphonate-associated osteonecrosis of the jaws. AJNR Am J Neuroradiol 2007;28:1139–45.
e11
[3] Marx R. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115–7. [4] Marx R, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567– 75. [5] Migliorati CA. Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol 2003;21:4253–4. [6] Migliorati C, Schubert M, Peterson D. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone. Cancer 2005;104:83– 93. [7] Wood J, Bonjean K, Ruetz S, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002;302:1055–61.