Bisphosphonate-Mediated Oral Ulcers: A Rare Differential Diagnosis of Erosive Oral Lesions

Abstract

Oral bisphosphonates are widely used drugs for the treatment of various indications such as postmenopausal osteoporosis. Ulcerations of the upper gastrointestinal tract, predominantly reported for alendronate, are common side effects. The occurrence of ulcerations within the oral cavity is less well known and probably underreported. Especially in cases of incorrect mode of intake, oral bisphosphonates are prone to induce oral ulcerations by as yet incompletely delineated mechanisms. We herein report on 2 elderly female patients suffering from oral ulcerations, which could be attributed to inadequate ingestion of alendronate. Possible ways to cause damage to the oral mucosa include non-specific toxic and pro-apoptotic effects, partly via bisphosphonate-mediated interference with intracellular signalling such as the mevalonate downstream pathway. Adequate patient advice in terms of correct use of oral bisphosphonates is crucial in order to prevent mucosal damage. Otherwise, prompt treatment cessation or a switch to an intravenously administered bisphosphonate is likely to achieve complete healing.

Augmentation of the cytotoxic effects of nitrogen-containing bisphosphonates in hypoxia

“…Moreover, it has been reported that fluvastatin, an HMG‐CoA reductase inhibitor, and ZOL have synergistic cytotoxic effects in pancreatic cancer cell lines . Oral bisphosphonate‐induced gastric damages are partly caused by interference with the mevalonate pathway . Magierowski et al .…”

A review and guide to drug‐associated oral adverse effects—Oral mucosal and lichenoid reactions. Part 2

“…Many case reports have been published regarding the association between the oral bisphosphonate alendronate and oral ulceration . Oesophageal and gastrointestinal ulceration are well‐established side effects of alendronate, but oral ulceration is less widely known .…”

“…44 Many case reports have been published regarding the association between the oral bisphosphonate alendronate and oral ulceration. 45,46 Oesophageal and gastrointestinal ulceration are well-established side effects of alendronate, but oral ulceration is less widely known. 45 Many case reports attribute the development of oral ulceration with incorrect use of the medication, where the patient keeps the tablet in the mouth for a prolonged period instead of immediately swallowing it.…”

“…45,46 Oesophageal and gastrointestinal ulceration are well-established side effects of alendronate, but oral ulceration is less widely known. 45 Many case reports attribute the development of oral ulceration with incorrect use of the medication, where the patient keeps the tablet in the mouth for a prolonged period instead of immediately swallowing it. 47 However, reports have surfaced in which the adverse reaction has occurred when alendronate has been administered appropriately.…”

Co-Presence of Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Squamous Cell Carcinoma in a Patient with Postmenopausal Osteoporosis: A Role for Chronic Traumatism?

“…Indeed, diagnostic suspect of BRONJ must be supported by radiological investigation: the most frequently used radiological investigations are, on a first level, the panoramic x-ray and the intraoral x-ray and on a second level the computer tomography scan (CT), both spiral CT and cone beam CT (CBCT) (second level investigation) [8]. Other common side effects are ulcerations of the upper gastrointestinal tract, predominantly reported for alendronate in its oral administration [9], especially when patients have not taken BPs as instructed (lying down within 30 minutes of taking the medication). In addition, in 2009, a US Food and Drug Administration suggested an association between bisphosphonates and risk of oesophageal cancer [10] but, to date, the association between oral bisphosphonate use and upper gastrointestinal cancer has not been established [7].…”