Clinical aspects of bisphosphonate-associated oral osteonecrosis in patients with multiple myeloma
Bisphosphonates are non-metabolised pyrophosphonates analogues that are absorbed on the durapatite crystals of the bone matrix slowing down both growth speed and break-up by strongly inhibiting osteoclast activity.
Their clinical use dates back to 30 years ago, and in the years they have been mainly used in onco-haematology for the treatment of patients suffering from severe malignancies with bone metastasis such as lung, breast and prostate cancer, in hypercalcemia of malignancy, in the treatment of multiple myeloma and they are also prescribed in the osteoporosis and Paget’s disease.
Several bisphosphonate molecules are on the market but the most widely used in the clinical setting are pamidronate and zolendronate.
Bisphosphonates act on osteoclasts blocking their function in several ways: inhibiting the osteoclast formation from monocytes, reducing the osteoclasts’ life cycle, inhibiting osteoclastic activity on the bone surface. At a molecular level, bisphosphonates are deemed to modulate osteoclast function interacting with a surface cell receptor or with an intracellular enzyme. Considering that they are not metabolised and have a strong binding affinity with osteoclasts, they produce their death (osteoclasts apoptosis). In addition to the anti-reabsorption effect on the bone, an anti-angiogenetic effect on animals has been recently described. Bisphosphonates can inhibit the endothelial cell function both in vivo and in vitro. The cells treated with bisphos- phonates have shown a decreased proliferation, an increased apoptosis and a reduced capillary vessels formation.
As to negative side effects, treatment with bisphosphonates produced flu-like symptoms, fatigue, gastrointestinal disorders, anaemia, dyspnoea and oedemas. Oral and oesophageal mucosal ulcerations were also observed. In 2003, following the clinical observations by Marx and Stern in patients suffering from myeloma, a possible implication of bisphosphonates in the development of maxillary osteonecrosis was postulated. Afterwards, this hypothesis was also supported by several Authors who highlighted a strong correlation between intra-oral bone necrosis and bisphosphonates treatment, in particular after tooth avulsion or other oral cavity surgery.
Hence, the aim of this article is to describe the clinical aspects of the osteo-necrotic lesions in a group of patients suffering from myeloma and treated with bisphosphonates. Furthermore, the possible pathogenetic mechanisms will be also dealt with because the authors are convinced that these lesions are a possible complication of bisphosphonates treatment.
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