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Osteonecrosis of the jaw as a serious adverse effect of bisphosphonate therapy and its indistinct etiopathogenesis.

Bisphosphonates (BPs) represent a class of drugs that are applied in therapy of different pathological conditions related to bone. Their main role in bone metabolism is to inhibit osteoclast function, so these drugs act as potent devices in suppression of the bone resorption process. Considering the presence of two phosphonate groups with a high affinity for calcium ions in their chemical structure, BPs have the ability to accumulate predominantly in bones . According to the differences in side chain, related to the presence or absence of nitrogen atom, BPs are classified in two different groups: nitrogen containing (aminoBPs) and non-nitrogen containing (non-aminoBPs) drugs. These two groups of bisphosphonates also differ in mechanism by which they inhibit osteoclast action. Aminobisphosphonates (pammidronate, neridronate, olpadronate, ibandronate, risedronate, zoledonate) act directly on HMG-CoA reductase (mevalonate) pathway by binding and blocking enzyme farnesil diphosphate synthetase (FPPS) . Non-amino bisphosphonates (etidronate, clodronate, tiludronate) are metabolised within osteoclasts to analogues of adenosine triphosphate (ATP) that accumulate within the cells, which leads to inhibition of numerous metabolic enzymes, cytotoxicity and apoptosis . Nitrogen addition greatly increases the potency of bisphosphonate, so aminoBPs are claimed to be 10–10,000 times more potent comparing non-aminoBPs . As they act as inhibitors of osteoclast function in order to suppress bone resorption and improve bone mineral density, during the past three decades, bisphosphonates have been increasingly used in therapy of diferrent pathologic conditions related to bone. Intravenous BPs are principally used for treatment of metastatic bone lesions, multiple myeloma and hypercalcemia of malignancy. Oral BPs take part in therapy of osteoporosis, Paget disease and paediatric osteogenesis imperfecta. Positive effects of bisphosphonates in these conditions are: significant reduction of bone pain, osteolytic lesions and fracture risk, and improvement of bone mineral density. BPs are considered as drugs of certified efficiency, with rare negative side effects, such as gastrointestinal intolerance, headache, hypocalcemia, hypophosphatemia, bone pain, dizziness, fever, fatigue etc. , probably due to their low serum concentration and rapid accumulation in bone matrix.