Lip Ulceration Associated with Intravenous Administration of Zoledronic Acid: Report of a Case

Abstract

Although osteonecrosis of the jaw is a well-known adverse reaction of bisphosphonates (BPs), random cases of oral mucosal ulceration after per os administration of BP-aledronate have been attributed to prolonged mucosal irritation. This report, for the first time, describes the mucosal ulceration related to intravenous use of zoledronic acid (ZA). A 52-year-old female patient presented with painful ulcers on both cutaneous/mucosal surfaces of the lower lip and a 2-month history of osteonecrosis of the mandible beside the right lower canine. Her medical record included intravenous administration of ZA for 10 months for primary breast cancer metastatic to bone. Examination of the peripheral blood showed severe anemia and a slightly increased white blood cell count, due to urinary tract infection by E. coli, but no evidence of a viral infection. The treatment of anemia and E. coli infection did not improve the labial ulcers. Biopsy from the mucosal lesion revealed a non-specific ulceration with moderate inflammatory infiltration. There was no evidence of infection or malignancy. ZA administration was discontinued and within 3 months the lesions were resolved after treatment with systemic antibiotics (amoxicillin), vitamins A and E, chlorexidine and H₂O₂ (hydrogen peroxide) solutions and local pantothenic acid/vitamin A creams. Recurrence was detected a month after ZA re-administration. Nevertheless, after new treatment, the patient was free of oral/skin lesions 18 months later. This case, which is the first report of ulceration associated with intravenous administration of bisphosphonates, suggests that systemic mechanisms may be implicated in BP-induced oral mucosal ulceration. Furthermore, ZA appears to cause the same oral mucosal manifestations as alendronate. This emphasizes the need for oral examination in all cases of BP therapy, whether per os or intravenously administrated.