Indeed, dasatinib decreased the osteolysis induced by prostate cancer cells injected into tibiae of SCID mice and inhibited the growth of cancer cells [ 51], while it reduced the expression of markers of bone resorption in patients with advanced castration-resistant prostate cancer [ 52].
Highly crosslinked polyethylene (XLPE) was introduced to decrease periprosthetic osteolysis related to polyethylene wear, a major reason for revision of total hip arthroplasty.
2ME2 was also previously shown to decrease osteolysis in a 4T1 breast cancer metastasis model [42].
Thus, a drug that stimulated RANKL+ cells in the osteoblast lineage could increase rather than decrease osteolysis and tumor growth.
While current therapies exist to decrease osteolysis and reduce sequella of bone metastases, there are few options to diminish bone tumor burden [ 19, 20].
Src is an important player in forming the cell cell junctions necessary for bone resorption to take place, and it has been clearly shown that inhibition of src activity decreases bone osteolysis.
Nevertheless, calcitonin led to decreased osteolysis, whereas a local or systemic inflammation due to injections would possibly have lead to increased osteolysis.
The critical role of RANKL/RANK signaling in CaP associated osteolysis has been demonstrated by studies showing that the inhibition of RANKL/RANK signaling decreases tumor associated osteolysis which subsequently results in decreased CaP growth in the bone environment [ 16, 18, 20, 35].
The highly cross-linked polyethylene liners currently used with modular uncemented cups have substantially decreased wear and osteolysis at early follow-up.
Gibon et al. showed in 2012 that a systemic therapeutic intervention in the MCP-1-CCR2 chemokine-receptor axis (CCR2 is the receptor for MCP-1) leads to less systemic migration of macrophages to the site of particle infusion and further, to decreased osteolysis [30,31].
