**3. Type of bone metastases**

In metastatic bone disease, the normal bone homeostasis that involves constant remodeling by the coordinated actions of osteoclasts and osteoblasts is disturbed [5, 7]. According to the primary mechanism of interference with normal bone remodeling, bone metastases can be classified as osteolytic, osteoblastic, or mixed [8].

**Osteolytic** lesions are characterized by the destruction of normal bone and are associated with high osteoclast activity and reduced osteoblast activity. Several factors secreted by tumor cells enhance osteoclast-mediated bone resorption, either directly (like interleukin-8) or indirectly [like the parathyroid hormone-related peptide (PTHrP), interleukin-6] via stimulation of the receptor activator of the nuclear

*Perspective Chapter: Bone Metastases of Solid Tumors DOI: http://dx.doi.org/10.5772/intechopen.108607*

factor kappa-B (RANK) ligand (RANKL) secretion and inhibition of osteoprotegerin (OPG) production by osteoblasts. In turn, the binding of RANKL to RANK on osteoclast precursors leads to the formation of new osteoclasts, increasing their activity [7]. This type of metastasis is characteristic of prostate cancer, small cell lung cancer, carcinoid tumors, and medulloblastoma.

**Osteoblastic** metastases are characterized by the deposition of new bone (osteosclerosis). Several factors secreted by tumor cells directly enhance osteoblast differentiation, like endothelin-1 (ET-1) and bone morphogenetic proteins (BMPs). The stimulation of osteoblast differentiation is associated with increased OPG production, whereas RANKL secretion is decreased, and tumor-derived ET-1 directly acts on mature osteoclasts to inhibit osteoclast activity. Therefore, there is a strong imbalance between bone formation and bone resorption, leading to aberrant bone formation [7]. This pattern is usually seen in renal cell cancer, non-small-cell lung cancer, melanoma, and thyroid cancer.

If a lesion has both osteolytic and osteoblastic components, it's classified as **mixed** and is usually seen in breast cancer, gastrointestinal cancers, and squamous cancers.
