Lack of response to teriparatide therapy for bisphosphonate-associated osteonecrosis of the jaw

Abstract

Dear Editor, Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate therapy. Its pathogenesis is multifactorial and seems to be the combined result of attenuated osteoblastic activity due to the patient's underlying disease and inhibition of bone resorption by bisphosphonates. This leads to defective bone remodelling and a consequent impairment in the ability to repair bone damaged by oral trauma such as dental extraction or implant or to maintain bone homeostasis (some cases occur spontaneously without associated trauma) [1]. Management of ONJ is a challenge, due to the lack of effective treatment. Recently, teriparatide was reported as an adjunctive therapy for this condition. Because teriparatide is a medication that exerts anabolic effects on bone, it has been suggested that this drug might be beneficial in situations in which bone repair must be stimulated. To date, six independent case reports have documented the efficacy of teriparatide in the management of severe bisphosphonate-related ONJ resistant to conventional therapy (Table 1) [2–7]. On the basis of this preliminary evidence, we tested teriparatide in another case of bisphosphonate-associated ONJ. The patient was a 79-year-old woman with a 3-year history of rheumatoid arthritis treated with oral methotrexate (15 mg weekly), naproxen (1 g daily), prednisone (5 mg/ daily) and rituximab (the last treatment cycle with 1 g, 2 weeks apart, had been administered 6 months previously). She also had osteoporosis treated with 1,200 mg of calcium with 800 IU of vitamin D daily and ibandronate 150 mg once monthly. After 32 months of bisphosphonate therapy, the patient developed spontaneous osteonecrosis of the right mandible, without evidence of associated osteomyelitis (Fig. 1). She was evaluated by an oral and maxillofacial surgeon and treated with antiseptic mouthwashes and oral amoxicillin, since there was no indication for incision and drainage. Ibandronate was stopped and replaced by teriparatide at a dose of 20 μg per day. Unfortunately, despite treatment with teriparatide for 8 months, the patient did not present any noticeable symptomatic benefit and the mandibular osseous defect did not substantially improve on control computed tomography (Fig. 1). Previous reports [2–7] suggest that there may be a therapeutic role for teriparatide in the management of severe ONJ in patients with non-malignant skeletal disease. However, the lack of response in our case challenges this impression. J. Narvaez (*) : C. Gomez-Vaquero : J. M. Nolla Department of Rheumatology (planta 10-2), Hospital Universitario de Bellvitge-IDIBELL, Feixa Llarga s/n. 08907, L Hospitalet de Llobregat, Barcelona, Spain e-mail: fjnarvaez@bellvitgehospital.cat