Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenomenon triggered by tumor cells eventually leading to both tumor proliferation as well as bone deregulation, thus fueling the development of bone metastasis.

Metastasis is, so far, an incurable disease. The skeleton is one of the most frequent sites of metastases, behind the lungs and liver. Prostate and breast cancers are responsible for the majority of bone metastases. Indeed, in prostate cancer the bone is often the unique site of metastasis, with a prevalence of up to 90%, while for breast cancer the prevalence is around 65%–75%.

Patients with bone metastases experience a very miserable quality of life, due to severe pain, spinal cord compression, fractures, bone marrow aplasia and hypercalcemia, the latter being the principal cause of death. In fact, hypercalcemia can induce gastrointestinal dysfunctions, as well as constipation, polyuria and fatigue. In the advanced stage, it is the leading cause of renal failure and cardiac arrhythmias. All these symptoms are usually classified as skeletal-related events (SREs).

Bone metastases can be classified, according to their radiological appearance, as osteolytic, osteosclerotic or mixed, the latter when both features are present in the same region. Osteolytic lesions are preferentially caused by breast cancer cells and are characterized by the complete destruction of bone and its substitution with a tumor mass. Since the bone is a hard tissue, this destruction seems to be necessary for tumor cells to make space for their growth.

Osteoclast differentiation transpires to be a complex process that can be divided in three major steps: (1) the commitment of the hematopoietic stem cells (HSCs) towards the macrophages lineage; (2) the acquisition of the positivity for the tartrate resistant acid phosphatase (TRAcP) enzyme and calcitonin receptor, thus giving rise to an osteoclast precursor and (3) the fusion of the osteoclast precursors eventually forming to mature polynucleated osteoclasts.

Feel free to share your research work on related topics in Journal of Orthopedic Oncology which offers information in all aspects of primary, malignant tumors. Osteosarcoma, Ewing's sarcoma, chondrosarcoma, chordoma, and soft tissue sarcomas etc., it also deals with diagnostic methods, therapeutic approaches, clinical, laboratory research and reconstructive techniques.

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Regards,

Stella

Editorial Team

Journal of Orthopedic Oncology