Advances in the understanding of myeloma bone disease and tumour growth.

Advances in multiple myeloma support the notion that the associated bone disease, characterized by increased osteoclastogenesis and suppressed osteoblastogenesis, is both a consequence and necessity of tumour progression. Osteoblastogenesis is suppressed by secreted inhibitors and dysregulation of cell-surface 'coupling' factors on osteogenic cells. Osteoclastogenesis is increased as a consequence of osteoblast deactivation and of production of osteoclast-activating factors. Osteoclasts express soluble and cell-surface factors that stimulate myeloma growth, while osteoblasts produce bone-building factors that restrain growth of myeloma cells that are dependent on the microenvironment; detailed molecular mechanisms are discussed. Experimental and clinical findings indicate that pharmacological and experimental osteoblast-activating agents that effectively promote bone formation also reduce growth of myeloma cells within bone, seemingly by simultaneously stimulating osteoblastogenesis and restraining osteoclastogenesis. Unravelling mechanisms of myeloma bone disease expands horizons for developing novel interventions and also facilitates better understanding of the association between induction of osteolysis and disease progression.