Bisphosphonate’s Effect on Tongue Mucosa: An Experimental Electron Microscopy Study

Abstract

Background and objectives: Bisphosphonates (BPs) are selective inhibitors of osteoclasts, used for the treatment of bone disorders. The objective of this study is to investigate the possible effects of BPs on the tongue’s mucosa. Materials and Methods: Specimens of the tongue of 20 female 12-month old Wistar rats were taken. Ten were used as control group, while in the remaining alendronate (Fosamax, Merck) was administered per os from 13 weeks. Observation of the harvested samples was made by Transmission Electron Microscopy (TEM). Results: In the experimental group, focal alterations were observed to various extent in all specimens. The basement membrane was intact. Furthermore, an increase at the intercellular space was observed, predominantly at the middle layer, and the desmosomes were disorganized. In the lamina propria focal edema was observed. Conclusions: Investigation on the effect of BPs on the tongue’s mucosa through TEM hasn’t been documented in the past. According to our results, BPs seem to cause mild mucosal lesions on the tongue.

Effect of Fosamax on the duodenal mucosa in adult male albino rats and the possible protection by nigella sativa oil: a histological and immunohistochemical study

“…Group III (Fosamax-treated group): Rats of this group were administered 0.05mg/kg of Fosamax dissolved in 0.5 ml of normal saline solution orally by a gastric tube once weekly for 13 weeks. The Fosamax dose was calculated according to the usual human dose [18] .…”

Bisphosphonate affects the behavioral responses to HCl by disrupting farnesyl diphosphate synthase in mouse taste bud and tongue epithelial cells

“…Bisphosphonates have been shown to affect the adhesion of various types of cells including epithelial cells 8 , endothelial cells 33 and cancer cells 34 . It has also been reported that bisphosphonates are associated with esophagitis and oral ulceration 8,26,35,36 . Experiments using in vitro models of the oral mucosa have shown that pamidronate and zoledronate reduce the viability, inhibit the proliferation and enhance the apoptosis of oral keratinocytes and fibroblasts.…”

Oral bisphosphonates: Adverse effects on the oral mucosa not related to the jaw bones. A scoping review

“…21 In a recent in vitro study has been suggested that the decrease in the number of hemidesmosomes noticed after administration of alendronic acid could indicate the formation of ulcerous lesions in murine buccal mucosa. 23 Consequently, bisphosphonates may interfere in regenerative, apoptotic and ultrastructural cellular processes, leading to the development of mucosal adverse effects.…”

“…Bisphosphonate toxicity to gastrointestinal cells is well documented 14,16,17 . Recent in vitro studies provide evidence that high doses of oral bisphosphonates may also have a negative impact on the oral mucosa 21‐24 . Doneti et al (2014) suggested that alendronic acid may have a negative effect on keratinised oral human mucosa of osteoporotic patients without clinical signs of MRONJ, 22 whilst recent experimental studies in animals have demonstrated that alendronic acid can induce an inflammatory process in the buccal and tongue mucosa 23,24 .…”

“… 14 , 16 , 17 Recent in vitro studies provide evidence that high doses of oral bisphosphonates may also have a negative impact on the oral mucosa. 21 , 22 , 23 , 24 Doneti et al (2014) suggested that alendronic acid may have a negative effect on keratinised oral human mucosa of osteoporotic patients without clinical signs of MRONJ, 22 whilst recent experimental studies in animals have demonstrated that alendronic acid can induce an inflammatory process in the buccal and tongue mucosa. 23 , 24 Furthermore, adverse effects on the oral soft tissues have been described in several case reports and are accompanied by pain and great discomfort for the patient, whilst a life‐threatening situation has also been described.…”