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

Abstract

Bisphosphonates are anti-resorptive agents highly efficient in binding bone hydroxyapatite. They can modulate the bone turnover and increase its mineral density. 1,2 Bisphosphonates are widely used to treat postmenopausal and corticosteroid-induced osteoporosis. 3 The use of bisphosphonates in osteoporosis has been shown to improve bone strength and decreases the risk of fracture. 4 Moreover, bisphosphonates are used in Paget's disease and fibrous dysplasia, 5 to balance metastatic cancer (primarily breast and prostate) deposits in bone, 6,7 to cure severe hypercalcemia 8 and to treat the bone resorption defects of multiple myeloma. 8 Some examples of widely used oral bisphosphonates are alendronate, risedronate, etidronate,

Bisphosphonate’s effect on the tongue in adult male albino rats and the possible protective role of rutin: light and scanning electron microscopic study

“…Moreover, there were inflammatory cell infiltration, dilated congested blood vessels in lamina propria and disrupted skeletal muscles fibers with wide spaces in between. These results were consistent with several case reports describing adverse impacts of BP on the oral soft tissues including mucositis and severe oral ulceration most frequently affecting the tongue [ 3 ]. Moreover, our findings were in line with other experimental studies [ 7 , 9 , 22 ] on the effect of alendronate in oral mucosa and the researchers detected epithelial degeneration or ulcers, perivascular and/or subepithelial cellular infiltration, reduction of the epithelial cell layers with basement membrane rupture, pyknotic nuclei and increase in the intercellular spaces between the epithelial cells with destroyed desmosomes.…”

“…BPs are synthetic analogues of pyrophosphate, highly efficient in binding bone hydroxyapatite. These agents perform anticatabolic role by changing osteoclast mobilization, differentiation and function, and/or by triggering apoptosis, thus leading to a reduction in bone resorption [ 2 , 3 ].…”

“…The therapeutic uses of BPs have been explored for many years with reports of many side effects [ 3 ]. Concerning the gastrointestinal tract, many adverse effects were documented including dyspepsia, abdominal pain, nausea, vomiting, bleeding, diarrhea, constipation, oral ulcers, esophagitis, esophageal ulcers, gastric ulcer, cancers of gastrointestinal tract, and hepatotoxicity [ 7 ].…”

“…There is evidence in some studies that oral BPs (including alendronate) in high doses may possess adverse effects on the mucosa of oral cavity with the induction of an inflammatory reaction in the tongue and buccal mucosa [ 7 - 9 ]. Moreover, several case reports have described negative impacts of oral BPs on the oral soft tissues of the patient such as great discomfort and pain [ 3 ].…”

The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw

“…tooth extraction), suppressed bone remodelling by antiresorptive agents, and inhibition of new blood vessel formation by antiangiogenic agents contribute to the disease ( Aghaloo et al, 2015 ). In addition, oral bisphosphonates can cause soft tissue toxicity which harms the mucosal layer ( Psimma et al, 2021 ). However, the prevalence of MRONJ caused by denosumab, which lacks soft tissue toxicity, is as high as bisphosphonates ( Stopeck et al, 2016 ; Srivastava et al, 2021 ), indicating it does not play a central role in disease development.…”