Paget disease of bone

Abstract

Purpose of review Paget disease of bone is a prevalent disorder of bone metabolism, described as the second most common bone disease to affect an aging population in the United States after osteoporosis. Although recent studies suggest a decrease in mortality rates in Great Britain between 1951 and 1970 and a decline in prevalence and severity from the 1970s to 1990s, Paget disease continues to affect an important segment of the population with progressive deformity of bone, pain, and impaired quality of life. This article reviews the theories of pathogenesis and examines some of the relevant epidemiologic data. The pivotal role of the osteoclast in mediating this disease is discussed, followed by a brief summary of the pathology, clinical features, the diagnostic approach to patients, and therapeutic experience with increasingly potent bisphosphonates. Recent findings The cause of the disorder remains elusive but may be a viral infection affecting osteoclasts in a genetically predisposed person. Recent advances in genetic research suggest that lesions affecting the signaling pathways of receptor for activation of nuclear factor-Kb (RANK) and its receptor are critical in the expression of familial and some sporadic Paget disease, but the environmental determinants and triggers remain controversial. Previous viral infections, pet ownership, and geographical differences are some of the features identified by epidemiologic studies that may play a causative role. Much progress is being made in characterizing pagetic osteoclasts further in terms of their altered structure and function and the likely role of cytokines and of the marrow microenvironment. Studies with nitrogen-containing bisphosphonates have demonstrated their efficacy in inducing clinical and skeletal improvement and biochemical remissions in most patients with Paget disease. Summary Although the cause of Paget disease remains enigmatic, progress continues in understanding of the pivotal role of the osteoclast in Paget disease, with an increasing number of factors now implicated in abnormal osteoclast structure and function. There have been major therapeutic advances with the availability of increasingly potent bisphosphonates with real potential for prevention of progressive changes and for long-lasting remissions in most patients with Paget disease.