Paget disease of bone.

Despite significant advances in management, Paget disease remains an enigmatic disorder. There are no animal models, and while its end result --a focal disorder of accelerated bone turnover--is easily recognized, the causes and evolution of the disorder remain uncertain. Recent evidence strongly implicates both genetic and environmental factors in its etiology. The authors consider some of the unresolved questions surrounding Paget disease, including the attenuating prevalence and severity of the disease; how these observations might be reconciled with an apparently highly penetrant genetic susceptibility; what the putative environmental triggers of Paget disease might be; and what relapse after treatment tells us. Most observations seem to fit best with the idea that Paget disease behaves as a multifocal benign neoplasm.