Osteoprotegerin Deficiency and Juvenile Paget's Disease

To the Editor: Whyte et al. (July 18 issue)¹ report that homozygous deletion of the gene encoding osteoprotegerin is a potential cause of juvenile Paget's disease in some Navajo patients. A deficiency of osteoprotegerin leads to unopposed effects of its ligand, receptor activator of nuclear factor κB (RANK) ligand, resulting in enhanced osteoclastic bone resorption and profound bone loss. Since osteoprotegerin also serves as a receptor antagonist for tumor necrosis factor–related apoptosis-inducing ligand (TRAIL),² one cannot rule out the possibility that excessive TRAIL effects contributed to the skeletal phenotype.Increased susceptibility to infectious and cardiovascular diseases in patients with juvenile . . .