Home > Bone Disease in Multiple Myeloma
Bone disease biology
Osteoclast-mediated bone resorption is balanced with osteoblast-mediated new bone formation.60 Any
disruptions to this delicate balance favoring resorption can result in bone loss, weakened structural
integrity and greater potential for bone complications known as skeletal related events, as previously
defined.52,56,60 In multiple myeloma, due to interactions between
the tumor cell and bone marrow stromal cells, the normal bone remodeling process becomes uncoupled on a
cellular level that strongly favors bone resorption.18,55,61,62
Normal bone remodeling: bone resorption balanced by bone formation55,63
Factors and cellular source
- ↑ MIP-1α; MM cells56
- ↑ IL-6; BMSCs, endothelial cells, osteoclasts56,64
- ↑ RANKL; BMSCs, osteoblasts, osteocytes, MM cells18,55,65
- ↓ OPG; BMSCs, osteoblasts, osteocytes18,55
- ↑ IL-3; MM cells, T cells66,67
- ↑ Sclerostin; osteocytes55
- ↑ DKK1; MM cells, osteocytes55
- ↑ sFRP-2; MM cells55
Abbreviations
- BMSC
- Bone marrow stromal cell
- DKK1
- Dickkopf homolog 1
- IL-3
- Interleukin-3
- IL-6
- Interleukin-6
- OPG
- Osteoprotegerin
- MIP-1α
- Macrophage inflammatory protein 1 alpha
- RANKL
- Receptor activator of nuclear factor kappa-B ligand
- sFRP-2
- Secreted frizzled related protein-2
Changes in the tumor microenvironment in multiple myeloma
In the bone marrow, interaction of myeloma cells with bone marrow stromal cells induces secretion of
cytokines and growth factors that play various roles in disease pathogenesis. In addition to increasing
anti-apoptotic signaling and expression in myeloma
cells, these factors contribute to the uncoupling of healthy bone remodeling. Increased osteoclast
formation and activity results in excessive bone resorption and decreased osteoblast formation and
activity results in markedly reduced bone formation in the vicinity of the myeloma cells. Excessive
osteolysis near tumor cells may further promote myeloma cell growth, contributing to the cycle of tumor
growth and bone destruction.55,56,61,62
