Paget's Disease

Oral presentation: Section A

Paget's disease is the second most common disorder of bone after osteoporosis [1], but remains something of a clinical and pathobiological enigma. Paget's disease has a slight male predominance but the clinical presentation and the effects of Paget's disease on the skeleton are similar in men and women. To date little information is available on the role gender differences may play, if at all, in Paget's disease. This is because little is known about the pathogenesis of the disorder, the basis for its highly localized nature [2], if a paramyxoviral infection or persistence of a virus is involved in the disease process, or the changes in the bone microenvironment that occur in the pagetic lesion. For more than thirty years evidence has accumulated that paramyxoviruses, especially measles virus, may contribute to the formation of the markedly abnormal osteoclasts that are present in pagetic lesions [3][4][5][6]. However, other investigators have not detected measles virus in pagetic osteoclasts [7]. In addition, there is a strong genetic component associated with Paget's disease. As many as 30% of Paget's patients have a first-degree relative affected with the disorder [8]. Recently, mutations have been identified in the sequestosome 1 gene in 30% of patients with both familial and 10-15% of patients with spontaneous Paget's disease [9][10][11]. However, the role these mutations play in the development of Paget's disease is still a subject of intensive investigation because not all persons harboring these mutations develop Paget's disease even though familial Paget's disease has a high penetrance. This presentation will briefly review the epidemiology, current understanding of the pathobiology, and clinical management of Paget's disease [12]. At the end, several new areas of investigation that may be pursued to further our understanding of the underlying mechanisms involved in the development of Paget's disease, will be discussed.

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