The cause of this disease is not known, the natural history poorly described and there is no clearly-defined systemic therapy. We propose a prospective observational study to investigate the natural history and pathogenesis of the disease. Some subjects will undergo standardized initial evaluation and medically indicated testing. Affected tissue will be sent for genetic testing to pursue the hypothesis that melorheostosis results from acquired somatic mutations in genes that control bone homeostasis. Enrolled subjects will be followed on an annual or biannual basis for assessment of disease progression and receive clinically indicated testing and treatment. The study of this rare bone disease offers the potential to generate new insights, provide answers as well as generate new questions into the biology of the skeletal and mineral metabolism.