Title:
Pharmacovigilance of oral bisphosphonates: adverse effects manifesting in the soft tissue of the oral cavity.

Abstract:
It is well known that oral bisphosphonates can induce necrosis of the osseous structures of the jaws. However, there seems to be a limited awareness that oral bisphosphonates can also induce adverse effects in the soft tissues of the oral cavity, as indicated by the paucity of reported cases in the literature. Because oral bisphosphonates are widely used drugs for several skeletal conditions, it is reasonable to assume that mucosal adverse effects are more common than the small number of published cases indicates. The purpose of this study was to investigate whether this adverse effect of bisphosphonates is represented as reports from health practitioners in an adverse drug reaction database, as well as to gain knowledge about which substances are being associated with adverse drug reactions affecting the oral mucosa.
The database of the Medical Products Agency-Sweden was searched for adverse effects from oral bisphosphonates manifesting in the oral and maxillofacial region. Reports of reactions limited to the soft tissues of the oral cavity were selected and further analyzed. Only those reports showing recovery or improvement after the cessation of bisphosphonate use were included in the study.
A total of 83 cases of adverse reactions to oral bisphosphonates were retrieved from the search. Of these, 12 were included in the study. They were associated with the use of alendronate, etidronate and risedronate, in descending order. Sixteen percent of the reports comprising the oral and maxillofacial region were limited to the oral mucosa and reported recovery or improvement after discontinuation of the drug.
Adverse effects of oral bisphosphonates with manifestations in the soft tissue of the oral cavity seem to be more common than the small number of published cases indicates. However, considering that oral bisphosphonates are widely used drugs, the incidence is still low. These adverse drug reactions are not limited to alendronate and may also be induced by etidronate and risedronate. Still, a significant proportion of the cases are associated with alendronate. Regardless of the substance used, discontinuing the drug is an effective treatment for the mucosal lesions.