Evidence of a role for RANKL in the development of myeloma bone disease

Curr Opin Pharmacol. 2004 Aug;4(4):340-6.  

Evidence of a role for RANKL in the development of myeloma bone disease.

De Leenheer E, Mueller GS, Vanderkerken K, Croucher PI.

Bone Biology Group, G Floor, Division of Clinical Sciences, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.

Multiple myeloma is associated with the development of a devastating bone disease mediated by increased osteoclastic activity. The ligand for receptor activator of nuclear factor-kappaB (RANKL) plays a critical role in normal osteoclast biology and is abnormally regulated in myeloma. Targeting this system with recombinant decoy receptor, osteoprotegerin, or soluble forms of the receptor activator of nuclear factor-kappaB is able to prevent myeloma bone disease in pre-clinical models. Intriguingly, inhibiting osteoclast formation and bone resorption, and altering the bone marrow microenvironment, results in an indirect anti-myeloma effect.