Risk factors and causes of the occurrence of medication-related osteonecrosis of the jaw

Medikamentozna osteonekroza čeljusti označava odumiranje koštanog dijela čeljusti kod pacijenata koji uzimaju antiresorptivnu terapiju, antiangiogene lijekove ili druge novije lijekove čija se povezanost s nastankom osteonekroze čeljusti još istražuje. Lijekovi koji se najčešće dovode u vezu s nastankom osteonekroze čeljusti su antiresorptivni lijekovi: bisfosfonati i denosumabi. Mehanizam djelovanja ovih lijekova je inhibicija funkcije osteoklasta, uz očuvanje funkcije osteoblasta i samim time povećanje koštane mase. Koriste se u liječenju koštanih poremećaja, najčešće osteoporoze, kod multiplog mijeloma ili kod pacijenata oboljelih od malignih bolesti. Medikamentozna osteonekroza isključivo pogađa čeljusne kosti, najvjerojatnije zbog visoke stope remodelacije kosti, tanke sluznice i prisutnosti velikog broja mikroorganizama u usnoj šupljini. Postoje različite teorije o nastanku MRONJ-a, to su inhibicija resorpcije i remodelacije, upala i infekcija, inhibicija angiogeneze, toksičnost mekih tkiva, imunološka disfunkcija i niske vrijednosti pH. Rizični čimbenici za nastanak MRONJ-a su način primjene lijeka, doza, potentnost lijeka i trajanje terapije, a uvjetovani su osnovnom bolesti pacijenta. Ostali su sistemski čimbenici: osnovna bolest, kemoterapija, radioterapija, terapija kortikosteroidima, šećerna bolest, anemija i drugo. U rizične lokalne faktore ubrajamo ekstrakciju zuba, parodontitis, ugradnju dentalnih implantata i neadekvatno izrađene proteze. Bitan su također faktor navike pacijenata poput pušenja te održavanje oralne higijene. S obzirom na kliničku sliku postoje četiri stadija MRONJ-a o kojima ovisi liječenje bolesti. Glavni je cilj liječenja podići kvalitetu pacijentova života. Nekrotični se dio kosti najčešće odstranjuje kirurškim putem, u terapiju se uključuju antibiotici, a nastali defekt sanira se na različite načine. Danas se koriste i adjuvantne terapije kao što su primjena lasera, autolognih faktora rasta i hiperbarične oksigenacijeMedication-related osteonecrosis of the jaw (MRONJ) represents dying of the jawbone tissue in patients receiving antiresorptive therapy, anti-angiogenic drugs or other newer medicines whose link to the development of osteonecrosis of the jaw is still being investigated. Drugs most commonly associated with osteonecrosis of the jaw are antiresorptive drugs: bisphosphonates and denosumab. The mechanism of action of these drugs is to inhibit osteoclast function, while preserving osteoblast function and, consequently to increase bone mass. They are used in the treatment of bone disorders, most commonly osteoporosis, multiple myeloma or with patients with malignant diseases. Medication-related osteonecrosis exclusively affects the jawbone, most likely due to high rates of bone remodelling, thin mucous membranes and the presence of a large number of microorganisms in the oral cavity. There are different theories about MRONJ occurrence, and some of them are as follows: resorption and remodelling inhibition, inflammation and infection, angiogenesis inhibition, soft tissue toxicity, immune dysfunction, and low pH levels. Risk factors for the onset of MRONJ are the mode of drug administration, dose, potency of the drug and the duration of therapy, conditioned by the patient's underlying illness. Other systemic factors include: primary disease, chemotherapy, radiotherapy, corticosteroid therapy, diabetes, anemia, etc. Local risk factors include tooth extraction, periodontitis, dental implants placement, ill-fitting dentures. The patient’s habits, such as smoking and maintaining oral health, are regarded as an important factor. According to the clinical manifestations, there are four stages of MRONJ, which the treatment of the disease depends on. The main goal of treatment is to raise the quality of the patient's life. The necrotic part of the bone is usually surgically removed, antibiotics are used in therapy, and the resulting defect is repaired in various ways. Adjuvant therapies are also used today, including laser, autologous growth factors and hyperbaric oxygenation