The histopathological evaluation of the local tolerance of alendronate containing medicines

Abstract

Introduction: In order to be effective, treatment for osteoporosis must be long-term. Unfortunately, according to clinical trials and clinical practice the most frequent cause of patient resignation from the treatment is adverse reactions to the medications. In the case of bisphosphonates they are most frequently connected with irritant impact of the drug on gastrointestinal mucosa. The aim of our study was to answer the question whether alendronate tablets coated with a thin neutral layer may protect gastrointestinal mucosa from the irritant effects of the active substance.
Material and methods: Three types of tablets were administered into the cheek pouches of 18 Syrian hamsters (divided into 3 experimental groups: I, II, III) i.e. regular alendronate tablets, coated alendronate tablets and placebo. The tablets were applied for 4 minutes a day on 4 consecutive days. 24 hours after the last application, the animals were sacrificed and segments of buccal tissue were taken for histopathological examination. Oral tissue reaction was assessed using the microscopic examination grading system developed by ISO. The following adverse changes of the tissue were recorded: epithelial lesions, leucocyte infiltration, vascular congestion and oedema. Later the irritation index was calculated.
Results: The irritation index was 11.0 (moderately irritant), 0.0 and 0.0 (none-irritant), in each group respectively.
Conclusion: It appears that the administration of the coated alendronate tablets reduces the frequency and intensity of the local adverse events from the gastrointestinal tract.