Metastatic Bone Disease Pathology

Metastatic bone disease is a complication of an advanced primary cancer elsewhere in the body. Certain cancers have a predilection for dissemination to the bone or skeleton. The uncontrolled growth and spread of abnormal cells characterize cancer. The environment in the skeletal system renders it prone to the spread of this fatal illness. The metastatic disease is also known as Secondary Cancers or Secondary Carcinomas, the primary being a cancer in another organ. Metastasis occurs when tumor cells of primary cancers in distant organs in the body travel to the bone by various methods.

The pathophysiology of the bone metastases is still unclear but the role of the osteoclast is definite. The physical properties of the circulation in the bone marrow like the capillary vasculature and sluggish blood flow are factors determining the establishment of metastasis. The distributions of bone metastasis and active bone marrow in the adult are correlated (DeBois, 2002, p. 218). The metastasis occurs through haematogenous spread or by direct spread from adjacent structures or through metastatic lymph nodes. Another path for dissemination exists when the spread occurs through the periosteal vessels to the cortical bone.

The elaborate vasculature pattern within the bone makes it a favorite place for metastasis. Amorphous gaps in the marrow sinuscoids allow the penetration and deposition of metastatic cells. .Five primary tumors of the breast, prostate, bronchi, thyroid and kidney lead to 80% of the metastatic bone cancers. The earliest sites detected would be the spine, pelvis and ribs. Later, the skull, femora, humeri, scapula and sternum are involved. The primary tumor does not influence or determine sites of metastasis. The endothelial cells of marrow sinuscoids have no basement membrane and the presence of amorphous gaps make entry easier.

(DeBois, 2002, p. 220). Chemoattractants have been suggested as another mechanism to attract the metastatic cells. Two classical forms of metastases are seen: the osteoclast and the osteoblast and sometimes both together. The incidence varies according to the primary. More than 80% are osteolytic and produce local bone destruction with a tendency for fractures. This is characteristic of metastasis from prostate carcinoma. The osteoclast has been considered as more important in the development and progression of bone metastasis (Clines, 2005, p. 151).

Osteoclastic activity is stimulated by the products of tumor cells, increased osteoblastic action causing increased production of receptor activator of nuclear factor kappa B ligand (RANKL) and through a deficiency of sex steroids which accompany the therapy of cancer (Clines, 2005, p. 157). Tumor cell migration begins with an angiogenesis followed by migration through extracellular matrix and extravasation into the blood stream (Clines, 2005, p. 159). For the process, extracellular matrix is degraded by the expression of some enzymes and when autocrine factors are released.

Tumor motility is thus stimulated (Mareel, 2003). The move to reach the bone probably is taken after the exit from the primary tumor by other interactions. Matrix metalloproteinases are believed to have a role in tumor cell invasion (Lynch et al, 2002). Initiation of bone resorption is through interstitial collagenase (Zhao, 1999). The bone also produces substances which cause tumor cells from primary breast cancer to develop an affinity to bone: the chemokine stromal-derived factor, SDF-1, which is released by bone, and its tumorexpressed receptor CXCR-4 (Muller, 2001).

Inhibition of bone metastasis is also possible through the alpha-v-beta 3 integrin on receptors in the tumor cells which regulate the osteoclastic binding and activation in bone in breast cancer metastasis. Cancer cells metastasize only in an advanced stage of the disease after an accumulation of pro-metastatic mutations (Clines, 2005, p. 160). Recent studies however show that many expressed genes from the tumor cells are necessary in breast cancers. Organ-specific metastasis therefore has a number of influencing factors. Bone derived transforming growth factor beta (TGFbeta) is an essential factor regulating tumor behavior.

The incidence of primary cancers that spread to the bone is as follows: prostate 230110, breast 217440, lung, 173770, kidney 35710 and thyroid, 23600 (Jacofsky, 2004, p. 22). These together contribute to 85% of the metastatic bone cancers. The number …

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