Table 5.

Enhanced Osteoclast Activation and Osteoclastogenesis With Lenalidomide and Bortezomib in Multiple Myeloma

	Lenalidomide	Bortezomib
Inhibitory target	PU.1* (transcription factor) pERK (transmembrane protein kinase)	Nuclear factor*
Impact on cell invasiveness	Decreases alpha V beta 3-integrin†
Effects on bone resorption	Decreases TRAP cells‡
Effects on RANKL	Decreases RANKL secretion of bone marrow stromal cells
Effects on cathepsin K§	Downregulates this protease

Abbreviations: RANKL, receptor activator of nuclear factor kappa B; TRAP, tartrate-resistant acid phosphatase.

^*Inhibition results in a decrease in osteoclastogenesis.

^†Membrane protein that works as a signaling factor in the regulation of osteoclast adhesion and activation.

^‡Tartrate-resistant acid phosphatase–positive cells that induce the destruction of articular cartilage, an osteoclast marker.

^§Essential for resorption of bone collagen matrix.

Data from Breitkreutz I, Raab MS, Vallet S, et al.

Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma.

Leukemia 2008;22:1925–1932.