Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is associated with many drugs, including bisphosphonates (BPs). BPs are associated with atypical femoral fractures and osteonecrosis of the external auditory canal. Thus, many drugs are reported to cause adverse effects on bone. This study aimed to investigate the effects of drugs and patient backgrounds regarding osteonecrosis-related side effects, including MRONJ. This study used a large voluntary reporting database, namely, the Japanese Adverse Drug Event Report database. First, we searched for risk factors related to MRONJ using volcano plots and logistic regression analysis. Next, we searched for bone-necrosis-related side effects using principal component and cluster analysis. Factors that were significantly associated with MRONJ included eight types of BPs and denosumab, prednisolone, sunitinib, eldecalcitol, raloxifene, letrozole, doxifluridine, exemestane, radium chloride, medroxyprogesterone, female, elderly, and short stature. Furthermore, antiresorptive agents (i.e., BPs and denosumab) tended to induce MRONJ and atypical femoral fractures by affecting osteoclasts. We believe these findings will help medical personnel manage the side effects of many medications.
Highlights
Since the first report by Marx [1], antiresorptive agents (i.e., bisphosphonates (BPs) and denosumab), or antiangiogenic agents have been reported to be associated with medication-related osteonecrosis of the jaw (MRONJ) [2,3,4,5]
This study study examined two key clinical questions concerning risk factors associated with MRONJ and the examined two key clinical questions concerning risk factors associated with MRONJ and the effects of effects of these drugs on other osteonecrosis-related side effects using the Japanese Adverse Drug these drugs on other osteonecrosis-related side effects using the Japanese Adverse Drug Event Report
Females and the elderly, short stature, eight types of BPs, denosumab, prednisolone, sunitinib, eldecalcitol, raloxifene, letrozole, doxifluridine, exemestane, medroxyprogesterone, and radium chloride were all factors associated with MRONJ
Summary
Since the first report by Marx [1], antiresorptive agents (i.e., bisphosphonates (BPs) and denosumab), or antiangiogenic agents (e.g., bevacizumab and tyrosine kinases inhibitors) have been reported to be associated with medication-related osteonecrosis of the jaw (MRONJ) [2,3,4,5]. Corticosteroids and novel immunomodulators have been reported to affect osteonecrosis of the jaw [6,7]. BP is reported to cause bone-related side effects, such as atypical femoral fractures and osteonecrosis of the external auditory meatus [8,9]. Discontinuation of resorption inhibitors is recommended for patients with risk factors, such as oral surgery and corticosteroid
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