Paget's Disease of Bone-Clinical Presentation and Diagnosis

Paget disease of bone (PD)-initially described by Sir James Paget in 1876-is a common benign bone disorder, which leads to the enlargement and deformity of bones due to a combination of abnormal bone resorption and abundant new bone formation. Genetic factors are important in the pathogenesis of PD and many families have been described where PD is inherited in an autosomal-dominant fashion. Several candidate loci for susceptibility to PD and related syndromes have been identified by genome-wide scans and recent evidence suggests that mutations in genes that encode components of the "receptor activator of nuclear factor-(NF-)kappa B" (RANKL)/NF-kappa B signalling pathway play an important role in the pathogenesis of this group of diseases. Furthermore, also a viral genesis has been elucidated causing PD. The clinical course of PD is characterized by chronic pain, bone deformations, and locally increased temperature of affected sites due to an increased vascular perfusion. PD can lead to fractures, neurological symptoms by nerve compression, or cardiac complications. However, only a small percentage of all patients with PD develops clinical symptoms and thus many Paget lesions remain undiagnosed or will be only detected by chance in the course of imaging performed due to other symptoms primarily not related to PD. The most important imaging method is conventional X-ray, which is capable of detecting early osteolytic Paget lesions. Bone scintigraphy shows hypermetabolic Paget lesions with high sensitivity. Computed tomography and magnetic resonance imaging are used for special questions such as possible malignant transformation. The most important laboratory parameter in PD is alkaline phosphatase, which is frequently elevated. An isolated elevation should initiate imaging procedures for diagnosing or excluding PD. In cases with unclear imaging results or in cases of possible malignant transformation to Paget-sarcoma bone biopsies will be needed.