**2. Antiresorptive and antiangiogenic medications**

#### **2.1. Bisphosphonates (BPs)**

Intravenous BPs are antiresorptive agents and administered for cancer–related conditions; hypercalcemia of malignancy, skeletal-related events (SREs) associated with bone metastases in the context of solid tumors (for example breast, prostate and lung cancers), and lytic lesions of multiple myeloma. These medications have a significant positive effect for the quality of life of patients with bone metastatic cancer [5]. Oral BPs are approved for the treatment of osteoporosis and osteopenia. They have been used in less common conditions, such as paget disease of bone and osteogenesis imperfection. The most common use is for osteopenia and osteoporosis [6].

#### **2.2. RANKL inhibitor (denosumab)**

The receptor activator of RANKL inhibitor (denosumab) inhibits osteoclast function and bone resorption. There is a decrease in the risk of vertebral, nonvertebral, and hip fractures in osteoporotic patients for administrating denosumab subcutaneously every 6 months. Moreover, monthly administration of denosumab is effective for decreasing SREs-related metastatic bone disease from solid tumors [7, 8]. In contrast to BPs, denosumab do not bind to bone and their effects of bone remodeling continue within 6 months [5].

#### **2.3. Antiangiogenic medications**

medications contain bisphosphonates and the receptor activator nuclear factor kB ligand

On the other hand, denosumab, a human IGG2 monoclonal antibody against RANKL, is a therapeutic agent for bone metastasis and osteoporosis, with a half-life of approximately 1 month. Unlike bisphosphonates (BPs), which promotes apoptosis in osteoclasts, denosumab inhibits osteoclastic bone resorption without causing apoptosis. Furthermore, denosumab is not deposited in the bone and thus does not persist for long periods of time, as is the case with BPs, and so the effects of denosumab are reversible [2]. However, patients treated with denosumab also developed ONJ (denosumab-related ONJ [DRONJ]), which was clinically

Since both BP and denosumab which show anti-bone resorption effects through different molecular mechanisms of action are associated with ONJ, antiresorptive agent-related ONJ (ARONJ) has been suggested as a comprehensive term encompassing both BRONJ and DRONJ [4]. The American Association of Oral and Maxillofacial Surgeons (AAOMS) has proposed the term "medication-related osteonecrosis of the jaw" (MRONJ), based on observations that antiangiogenic inhibitors and molecularly targeted drugs such as tyrosine kinase inhibitors are also infrequently associated with ONJ or increase the incidence of BRONJ/ DRONJ in cancer patients receiving BPs or denosumab, although global consensus has not

The number of patients with MRONJ has grown recently. Medication-related osteonecrosis of the jaw (MRONJ) is defined as exposed bone in the oral cavity or extra-oral fistula in the maxillofacial region for more than 8 weekswith the treatment of antiresorptive or antiangiogenic agents for more than 8 weeks. These patients have no history of radiotherapy or metastatic disease in the jaw. We present about the details, pathophysiology, diagnosis, staging and

Intravenous BPs are antiresorptive agents and administered for cancer–related conditions; hypercalcemia of malignancy, skeletal-related events (SREs) associated with bone metastases in the context of solid tumors (for example breast, prostate and lung cancers), and lytic lesions of multiple myeloma. These medications have a significant positive effect for the quality of life of patients with bone metastatic cancer [5]. Oral BPs are approved for the treatment of osteoporosis and osteopenia. They have been used in less common conditions, such as paget disease of bone and osteogenesis imperfection. The most common use is for osteopenia and osteoporosis [6].

The receptor activator of RANKL inhibitor (denosumab) inhibits osteoclast function and bone resorption. There is a decrease in the risk of vertebral, nonvertebral, and hip fractures

treatment, risk factor, and prevention of MRONJ in below paragraphs in this chapter.

**2. Antiresorptive and antiangiogenic medications**

indistinguishable from BRONJ and occurred at almost the same rates [3].

(RANKL) inhibitor [1].

88 Osteonecrosis

yet been established [5].

**2.1. Bisphosphonates (BPs)**

**2.2. RANKL inhibitor (denosumab)**

Angiogenesis inhibitors interfere with the formation of new blood vessels by connecting to many signaling molecules and disrupting the angiogenesis-signaling cascade. These medications are administered for gastrointestinal tumors, renal cell carcinoma, neuroendocrine tumors, and other malignancies [5].
