Denture-Related Osteonecrosis of the Maxilla Associated With Oral Bisphosphonate Treatment
Liran Levin, DMD,
Amir Laviv, DMD and
Devorah Schwartz-Arad, DMD, PhD
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ABSTRACT
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Background. Bisphosphonates are a class of agents used to treat various systemic conditions. Despite the benefits of bisphosphonates, osteonecrosis of the jaws is an important complication in a subset of patients who receive this drug treatment.
Case Description. A 66-year-old woman was referred to an oral surgeon at a private surgical center because of a pressure wound in the margins of a removable maxillary denture. The patient reported that she had received oral alendronate sodium treatment for eight years. A clinical examination revealed a palatal ulcer with exposed necrotic gray bone at its center. The clinician performed an excisional biopsy and separated two palatal rotational flaps to enable an adequate blood supply to reach the operated-on area.
Clinical Implications. This report, together with growing evidence in the literature, serves to alert treating physicians and dental practitioners about the potential complication of maxillary and mandibular bone necrosis in patients receiving bisphosphonate therapy.
Key Words: Pressure wound; denture; bisphosphonate; osteoporosis; osteonecrosisAbbreviations: AAOMS: American Association of Oral and Maxillofacial Surgeons
Bisphosphonates, pyrophosphate analogs, are strong osteoclast inhibitors that are used to treat osteoporosis, as well as solid tumors with bony metastasis. Clinicians also prescribe bisphosphonates for the treatment of malignant hypercalcemia, osteolysis associated with metastatic bone disease and Paget’s disease.
The literature contains an increasing number of reports of osteonecrosis associated with the nitrogen-containing bisphosphonates (pamidronate disodium and zoledronic acid). Oral surgeons most commonly have seen and treated these patients. An untreated maxillary osteonecrosis can lead to pansinusitis.1
During the past few years, investigators have reported an increasing number of cases of osteonecrosis of the jaw.2,3 Osteonecrosis of the jaw most often is identified in patients with cancer who are receiving intravenous bisphosphonate therapy, but it also has been diagnosed in patients receiving oral bisphosphonate therapy for nonmalignant conditions. The condition involves exposed bone of the maxilla or mandible. Although it often is associated with a recent dental surgical procedure, spontaneous osteonecrosis of the jaw also can occur. Patients commonly have symptoms such as pain, swelling and an unhealed ulcer with an exposed necrotic bone. Van Poznak and Estilo2 estimated that the incidence of osteonecrosis of the jaw in patients with cancer who receive intravenous bisphosphonate therapy ranges between 1 and 10 percent.
The aim of this report is to present a case of spontaneous denture-related osteonecrosis of the jaw associated with oral bisphosphonate treatment.
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REPORT OF A CASE
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A 66-year-old woman was referred to one of us (D.S.-A.) at a private surgical center (Schwartz-Arad Surgical Center, Ramat-Hasharon, Israel) after complaining for several months of a pressure wound in the margins of a removable partial maxillary denture. She also complained of a dull persistent pain in that area.
Her medical history revealed controlled hypertension and controlled hypercholesterolemia. The patient reported that she had taken alendronate sodium orally (10 milligrams per day) for six years, followed by 70 mg once a week for two years.
The clinical intraoral examination revealed a 0.5-centimeter palatal ulcer with exposed necrotic gray bone at its center, close to the soft-palate border (Figure, A
). The margins of the lesion were slightly elevated and pale. The posterior margin of the denture was defined clearly at the posterior section of the lesion. The clinician performed an excisional biopsy of the soft and hard tissues under local anesthesia, taking care not to rupture the floor of the nose (Figure, B). She separated two palatal rotational flaps to allow an adequate blood supply to the operated-on area. The oral surgeon sutured the flaps to the bone via holes made in advance (Figure, C).
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Figure. A. Preoperative view of the pressure wound. Note the posterior margin of the denture clearly defined at the posterior section of the lesion. B. The oral surgeon performed an excisional biopsy of the soft and hard tissues. C. The oral surgeon separated two palatal rotational flaps and sutured them to the bone via holes made in advance. D. Six months after surgery, tissue healing was observed.
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Postoperative instructions included use of a 0.2 percent chlorhexidine gluconate mouthrinse twice a day for 10 days and treatment with oral amoxicillin (500 mg three times a day for 10 days), followed by doxycycline hydrochloride (100 mg/day for an additional 10 days). Histopathologic findings included necrotic (non-vital) compact bone. The prolonged healing period (six months) (Figure, D
) was accompanied by two episodes of nonsurgical removal of bone sequestra.
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BISPHOSPHONATES
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Bisphosphonates are a class of agents used to treat osteoporosis, multiple myeloma and symptoms associated with cancer metastases to the bone. Despite the benefits of bisphosphonates, osteonecrosis of the jaws is an important complication in a subset of patients who are treated with these drugs. Based on a growing number of reports,2–4 bisphosphonate therapy may cause exposed and necrotic bone that is isolated to the jaw. The selective involvement of the maxilla and mandible may reflect the unique environment of the oral cavity.
Typically, healing of an open bony wound (for example, an extraction socket or a denture pressure wound) in the presence of normal oral microflora occurs quickly and uneventfully. However, when the healing potential is compromised, minor injury or disease in these sites increases the risk of developing osteonecrosis. The potential for complications in patients with a history of oral bisphosphonate use probably is related to the duration of exposure.2,4
This complication usually manifests after dentoalveolar surgery, but it can develop even without surgical intervention, as was the case with our patient. The pathogenesis appears to be related to the profound inhibition of osteoclast function and bone remodeling.2,3,5 Our case is an example of osteonecrosis that developed in the jaws after eight years of oral bisphosphonate therapy. Most reports relate to complications resulting from intravenous bisphosphonate therapy.1,4,5 Based on data from the manufacturer of alendronate (Merck & Co., Whitehouse Station, N.J.), the incidence of bisphosphonate-related osteonecrosis of the jaws was calculated to be 0.7 per 100,000 person-years of exposure in 2006.6
This report, together with growing evidence in the literature, serves to alert treating physicians and dentists about the potential complication of maxillary and mandibular bone necrosis in patients receiving bisphosphonate therapy. Bisphosphonate-related osteonecrosis in these patients may be a more significant problem than was first thought,7,8 given the large number of patients receiving oral bisphosphonate therapy.
The rationale for surgically treating this patient with stage II osteonecrosis of the jaws was based on this surgeon’s experience and clinical judgment at the time (during 2004), as well as on the patient’s lack of response to a conservative treatment regimen involving the use of a chlorhexidine mouthrinse. The aim was to provide a better blood supply by rotating two flaps that contained the greater palatine artery over the damaged area. It is noteworthy, however, that this is not the current recommended treatment.6
Recently, the American Association of Oral and Maxillofacial Surgeons (AAOMS) published a position paper on bisphosphonate-related osteonecrosis of the jaws.6 It included recommendations and guidance for clinicians with regard to possible prevention measures and treatment of patients with bisphosphonate-related osteonecrosis of the jaws based on the presenting stage of the disease.6 Although oral bisphosphonate therapy is not considered an absolute contraindication in patients who seek elective dentoalveolar surgery, the AAOMS 6 suggested that patients be adequately informed of the potential risk of compromised bone healing and the risk of developing bisphosphonate-related osteonecrosis. Clinicians also should follow up patients carefully until surgical wounds are healed completely.
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CONCLUSION
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This case report, together with the increasing evidence in the literature, serves to alert treating physicians and dentists about the potential complication of maxillary and mandibular bone necrosis in patients receiving bisphosphonate therapy.
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FOOTNOTES
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Dr. Levin is a clinical instructor, Department of Oral Rehabilitation, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Israel, and Unit of Periodontology, Department of Oral and Dental Sciences, Rambam Medical Center, Haifa, Israel.
Dr. Laviv is a resident, Department of Oral and Maxillofacial Surgery, Hebrew University-Hadassah School of Dental Medicine, Jerusalem.
Dr. Schwartz-Arad is a senior lecturer, Department of Oral and Maxillofacial Surgery, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel 69978, e-mail "dubi{at}dsa.co.il". Address reprint requests to Dr. Schwartz-Arad.
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REFERENCES
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- Van Poznak C, Estilo C. Osteonecrosis of the jaw in cancer patients receiving IV bisphosphonates. Oncology (Williston Park) 2006;20(9):1053–62.[Medline]
- Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102(4):433–41.[Medline]
- Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006;144(10):753–61.[Abstract/Free Full Text]
- Chaiamnuay S, Saag KG. Postmenopausal osteoporosis: what have we learned since the introduction of bisphosphonates? Rev Endocr Metab Disord 2006;7(1–2):101–12.[Medline]
- Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2007;65(3):369–76. Available at: "www.aaoms.org/docs/position_papers/osteonecrosis.pdf". Accessed April 4, 2007.[Medline]
- Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic (letter). J Oral Maxillofac Surg 2003;61(9):1115–7.[Medline]
- Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff S. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62(5):527–34.[Medline]
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ABSTRACT
REPORT OF A CASE
