Pagetʹs disease and osteoclast biology

Pagetʹs disease is the most exaggerated example of bone remodeling in which osteoclastic bone resorption remains coupled to new bone formation. There are abnormalities in the stages of osteoclast development, and studies in Pagetʹs disease have suggested a major role for IL-60 in human osteoclast activity. The pathophysiologic basis for these abnormalities is not clearly defined, except that the primary cellular abnormality resides in the osteoclast. Many important questions about the pathophysiology of Pagetʹs disease still remain to be answered, including: (1) What is the identity of the virus in pagetic osteoclasts?; (2) Are Pagetʹs patients in different geographical locales harboring a similar virus in their osteoclasts, or can different paramyxoviruses induce Pagetʹs Pagets disease?; (3) How is the virus maintained and propagated for many years, so that it can be expressed in the osteoclasts, a cell with a finite lifespan?; and (4) Since Pagetʹs disease has a very high familial tendency, with up to 40% of patients having an affected relative, what is the genetic locus associated with Pagetʹs disease, and does this genotype result in an increased propensity for hematopoietic cells such as the osteoclast to harbor paramyxoviruses? The application of the techniques of molecular and cell biology to Pagetʹs disease should provide answers to some of these questions and give important insights into the normal bone remodelling process.