Mechanisms of lytic and blastic metastatic disease of bone

In the majority of skeletal metastases, new bone develops simultaneously with bone destruction. The roentgenogram indicates the net effect of these two processes. Where the bone formation predominates, the lesion appears sclerotic. Where bone destruction predominates, it appears lytic. Mixed lesions may also occur. There are two main mechanisms for the new bone formation. Those tumors associated with a suitable fibrous stroma develop islands of intramembranous ossification within the stroma, e.g., metastases from prostatic carcinoma. In the vast majority of metastases bone destruction is associated with reactive new bone formation. The latter is similar to callus associated with fracture repair. Myelomata and lymphomata are not associated with this reactive new bone formation. There are at least two main mechanisms for the bone destruction. The earlier and quantitatively more important phase is mediated via osteoclasts, neoplasms secreting a variety of osteoclast stimulating factors. The main humoral factor in myeloma and the lymphomata is probably osteoclast activating factor (OAF), whereas in the carcinomata it may be prostaglandin. Two thirds of human mammary carcinomata are osteolytically active in vitro. In a co-culture model, the osteolysis can be significantly reduced by prostaglandin inhibitors, diphosphonates and particularly, their combination. At a late stage, neoplastic or monocytic cells are directly responsible for the continuing bone destruction.