Osteoblast function in myeloma.
Multiple myeloma (MM) is the most frequent cancer to involve the skeleton and results in purely osteolytic lesions that rarely heal. MM bone disease is responsible for some of the most devastating complications of MM. The marrow microenvironment plays a key role in MM bone disease as well as in the initiation, expansion and chemoresistance of MM cells. How this microenvironment becomes so supportive of MM, and the contribution and interaction of the various components of the microenvironment to enhancing MM growth are only beginning to be understood. However, it is clear that suppression of osteoblast activity plays a key role in the bone destructive process as well as progression of the tumor burden in myeloma. The impairment of osteoblast activity in MM results primarily from blockade of osteogenic differentiation of mesenchymal progenitors to mature osteoblasts. MM patients have low to normal levels of bone formation markers, such as alkaline phosphatase and osteocalcin in the setting of increased bone resorption. In contrast, MM patients without bone lesions display balanced bone remodeling with increased osteoclastogenesis and normal or increased bone formation rates. Both soluble factors and cell-to-cell contact between MM cells and osteoblast progenitors are responsible for the suppression of osteoblast differentiation in MM. In this article, the mechanism responsible for osteoblast suppression will be reviewed, and the effects of novel bone anabolic agents on myeloma bone disease will be discussed.
Roodman
G David
GD
Veterans Affairs Pittsburgh Healthcare System, Research and Development, Pittsburgh, Pennsylvania, USA. roodmangd@upmc.edu
D000469:Alkaline Phosphatase / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology* / Q000503:physiopathology; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology*; D015675:Osteocalcin / Q000494:pharmacology / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology
D015675:Osteocalcin; D000469:Alkaline Phosphatase