page_title: Medication-related osteonecrosis of the jaw
section_title: Pathogenesis
hierarchical_section_title: Medication-related osteonecrosis of the jaw / Pathogenesis
caption_attribution_description: Čeština: Mnohojaderný osteoklast na mikrofotografii. English: Osteoclast displaying many nuclei within its "foamy" cytoplasm. Osteoclast. हिन्दी: अपने "झागदार" कोशिका-द्रव्य में कई नाभिक प्रदर्शित करते हुए अस्थिशोषक. ಕನ್ನಡ: "ಫೋಮಿ" ಸೈಟೋಪ್ಲಾಸಂನಲ್ಲಿ ಹಲವು ಜೀವಕೋಶಗಳ ಇರುವುದನ್ನು ಆಸ್ಟಿಯೋಕ್ಲಸ್ಟ್‌ ತೋರಿಸುತ್ತದೆ. Polski: Osteoklast. Slovenščina: Osteoklast z vidnimi jedri. தமிழ்: அதனுடைய "நுரைப்போன்ற" திசுப்பாய்மத்தினுள் பலக் கருக்களை எலும்புத்திசு காட்டுகிறது. తెలుగు: తన "నురుగు"లాంటి కణద్రవ్యంలో అనేక కేంద్రకాలను చూపించే ఎముక విచ్ఛిన్న కణాలు.
context_page_description: Medication-related osteonecrosis of the jaw is progressive death of the jawbone in a person exposed to a medications known to increase the risk of disease, in the absence of a previous radiation treatment. It may lead to surgical complication in the form of impaired wound healing following oral and maxillofacial surgery, periodontal surgery, or endodontic therapy.
  Particular medications can result in MRONJ, a serious but uncommon side effect in certain individuals. Such medications are frequently used to treat diseases that cause bone resorption such as osteoporosis, or to treat cancer. The main groups of drugs involved are anti-resorptive drugs, and anti-angiogenic drugs.
  This condition was previously known as bisphosphonate-related osteonecrosis of the jaw because osteonecrosis of the jaws correlating with bisphosphate treatment was frequently encountered, with its first incident occurring in 2003. Osteonecrotic complications associated with denosumab, another antiresorptive drug from a different drug category, were soon determined to be related to this condition.
context_section_description: Although the methods of action are not yet completely understood, it is hypothesized that medication-associated osteonecrosis of the jaw is related to a defect in jaw bone healing and remodelling.
  The inhibition of osteoclast differentiation and function, precipitated by drug therapy, leads to decreased bone resorption and remodelling. Evidence also suggests bisphosphonates induce apoptosis of osteoclasts. Another suggested factor is inhibition of angiogenesis due to bisphosphonates; this effect remains uncertain. Several studies have proposed that bisphosphonates cause excessive reduction of bone turnover, resulting in a higher risk of bone necrosis when repair is needed.
  It is also thought that bisphosphonates bind to osteoclasts and interfere with the remodeling mechanism in bone. To be more specific, the drug interferes with the cholesterol biosynthesis pathway through the inhibition of farnesyl diphosphate synthase. Over time, the cytoskeleton of the osteoclasts loses its function and the essential border needed for bone resorption does not form. Like aminobisphosphonates, bisphosphonates have shown to have antiangiogenic properties. Therefore, effects include an overall decrease in bone recycling/turnover as well as an increased inhibition of the absorptive bone abilities.
  One theory is that because bisphosphonates are preferentially deposited in bone with high turnover, it is possible that the levels of bisphosphonate within the jaw are selectively elevated. To date, there have been no reported cases of bisphosphonate-associated complications within bones outside the craniofacial skeleton.
caption: Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.
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