A short account of metastatic bone disease

Abstract

In adults, bone is the preferential target site for metastases from primary cancers of prostate, breast, lungs and thyroid. The tendency of these cancers to metastasize to bone is determined by the anatomical distribution of the blood vessels, by the genetic profile of the cancer cells and by the biological characteristics of the bone microenvironment that favour the growth of metastatic cells of certain cancers.Metastases to bone may have either an osteolytic or an ostoblastic phenotype. The interaction in the bone microenvironment between biological factors secreted by metastatic cells, and by osteoblasts and osteoclasts, and the osteolytic and osteoblastic factors released from the organic matrix mediate a vicious cycle characterized by metastatic growth and by ongoing progressive bone destruction. This interaction determines the phenotype of the metastatic bone disease.

The active role of osteoporosis in the interaction between osteoblasts and bone metastases

“…attracting and activating the osteoclasts by the RANK/RANKL/OPG pathway[27][28][29][30] or directly by acting on the mononuclear cells or osteoclasts[6,31].Finally, by performing an invasion assay in this study we also invesdifferences between TW and CM for CICP, ALP and Alamar (only for OVX osteoblasts), thus confirming that the data obtained in the indirect co-culture system are similar to those of the direct co-culture system.However, in the case of direct co-cultures involving Transwell and cross-talking cell populations, we could not distinguish which was due…”

MRI for the detection of prostate cancer origin vertebral metastases in the preosteoblastic phase

“…Skeletal metastasis is preceded by a series of processes—the escape of metastatic cells from the primary prostate cancer into the blood stream, the establishment of marrow metastasis, proliferation within the marrow, promotion of osteoclastic and obsteoblastic activity leading to cortical bone invasion and overproduction of disorganised bone, which manifests radiologically/pathologically as the well-known ‘osteoblastic metastasis’ 4 7…”

“…Vertebral metastases are bloodborne metastases, which are very common in prostate cancer because of unique bone-trophic properties of prostate cancer cells. Invasion of the marrow, via the blood stream is the first step in the order of sequences leading to the development of an osteoblastic lesion which would ultimately be visualised on x-ray-based imaging modalities as well as on bone scans 3 4. However, in the time window between marrow invasion by prostate cancer cells, to the development of osteoblastic lesions, imaging of the marrow with the help of MRI could lead to the diagnosis of ‘preosteoblastic’ vertebral metastases.…”

ecancermedicalscience

“…The process of breast cancer metastasis, including tumour cell seeding, tumour dormancy, and metastatic growth, is only partly understood [5]. Bone is the first site of distant disease in 25–40% of patients with metastatic breast cancer, and up to 60–80% of patients with recurrent breast cancer eventually show evidence of skeletal involvement [6].…”

“…Complex biological pathways, including inflammation [7, 8], angiogenesis [9], invasion [10], osteoclastic activation, and bone matrix degradation, are involved in the formation of bone metastases [5]. Although the current diagnosis of bone metastases relies on bone imaging techniques, they are not sensitive enough for early detection and are invasive and expensive to use [11].…”