Osteosarcoma and metastasis associated bone degradation—a tale of osteoclast and malignant cell cooperativity

Cancer‐induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer‐dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast‐mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast‐mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer‐associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer‐associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.