Metastatic Bone Disease

Metastatic bone disease develops when malignant cells travel to bone, establish tumour deposits, and disrupt normal remodelling. Breast, prostate, lung, kidney, and thyroid cancers commonly spread to the skeleton, although any malignancy can do so. Bone destruction is often driven by a self-reinforcing feedback loop. Tumour cells release mediators such as parathyroid hormone-related protein (PTHrP), which stimulate osteoblasts and stromal cells to increase receptor activator of nuclear factor kappa-B ligand (RANKL) and reduce osteoprotegerin. RANKL promotes osteoclast maturation. Osteoclasts then resorb bone and release matrix-bound growth factors, including transforming growth factor beta and insulin-like growth factors, which encourage further tumour growth and PTHrP production. The tumour and the bone therefore sustain each other. Lesions may be: - Osteolytic: bone is resorbed faster than it is rebuilt. Multiple myeloma and many breast, lung, and renal cancers produce this pattern. - Osteoblastic: abnormal new bone is laid down, classically with prostate cancer. - Mixed: destructive and sclerotic features coexist. Osteolysis is most directly associated with hypercalcaemia and loss of structural strength. Osteoblastic lesions are not benign or reliably strong; the newly formed...