summary Paget's Disease is an idiopathic condition of abnormal bone remodeling with normal bone being replaced through an active interplay between excessive bone resorption and abnormal new bone formation. The condition typically present in patients age > 40 with asymptomatic lesions discovered incidentally on radiographs. Diagnosis is made with radiographs showing characteristic findings of lesions with diffuse blastic appearance and labs showing elevated serum ALP and elevated urinary collagen cross-links. Treatment is observation for asymptomatic patients. Medical management with bisphosphonates is indicated in symptomatic patients. Epidemiology Demographics peak incidence in the 5th decade of life common in Caucasians (northern European / Anglo-Saxon descent) males = females Anatomic location may be monostotic or polyostotic common sites include femur > pelvis > tibia > skull > spine Etiology Pathophysiology increased osteoclastic bone resorption is the primary cellular abnormality cause is thought to be a slow virus infection (intra-nuclear nucleocapsid-like structure) paramyxovirus respiratory syncytial virus Genetics inheritance most cases are spontaneous hereditary login to view 1 more bullet genetics most important is 5q35 QTER (ubiquitine binding protein sequestosome 1) SQSTM1 (p62/Sequestosome) login to view 1 more bullet also insertion mutation in TNFRSF11A for gene encoding RANK Orthopaedic manifestations bone pain long bone bowing fractures, due to brittle bone and tend to be transverse large joint osteoarthritis excessive bleeding during THA malalignment during TKA secondary sarcoma Associated conditions high output heart failure Classification Phases lytic phase intense osteoclastic resorption mixed phase resorption and compensatory bone formation sclerotic phase osteoblastic bone formation predominates all three phases may co-exist in the same bone Presentation Symptoms asymptomatic frequently asymptomatic and found incidentally pain pain may be the presenting symptom due to login to view 2 more bullets new intense pain and swelling login to view 1 more bullet cardiac symptoms can present with high-output cardiac failure particularly if large/multiple lesions & pre-existing diminished cardiac function Imaging Radiographs coarsened trabeculae which give the bone a blastic appearance both increased and decreased density may exist depending on phase of disease login to view 7 more bullets remodeled cortices loss of distinction between cortices and medullary cavity long bone bowing bowing of femur or tibia fractures hip and knee osteoarthritis osteitis circumscripta (cotton wool exudates) in skull Paget's secondary sarcoma shows cortical bone destruction soft tissue mass MRI may show lumbar spinal stenosis Bone scan accurately marks site of disease intensely hot in lytic and mixed phase less hot in sclerotic phase CT scan cortical thickening and coarsened trabeculae Evaluation Laboratory findings elevated serum ALP elevated urinary collagen cross-links elevated urinary hydroxyproline (collagen breakdown marker) increased urinary N-telopeptide, alpha-C-telopeptide, and deoxypyridinoline normal calcium levels Histology Characteristic histology woven bone and irregular broad trabeculae with disorganized cement lines in a mosaic pattern profound bone resorption - numerous large osteoclasts with multiple nuclei per cell virus-like inclusion bodies in osteoclasts Paget's osteoclasts larger, more nuclei than typical osteoclasts fibrous vascular tissue interspersed between trabeculae Differential Differential of Paget's Disease Benign lesion in older patient (40-80) Multiple lesions in the older patient Treatment is Observation only (assuming no imp. path. fx.) Benefits from Bisphosphonate therapy Paget's disease o o o o Enchondroma o o Bone island o Bone infarct o o Hyperparathyroidism o o Metastatic bone disease o o Myeloma o o Lymphoma o NOF o Osteochondroma o Eosinophillic granuloma o Fibrous Dysplasia o Treatment Nonoperative observation and supportive therapy treatment for asymptomatic Paget's disease login to view 1 more bullet medical therapy aimed at osteoclast inhibition bisphosphonates are 1st line treatment for symptomatic Pagets login to view 12 more bullets calcitonin are 2nd line (after bisphosphonates) login to view 2 more bullets teriparatide is contraindicated in Paget's disease due to risk of secondary osteosarcoma Operative THA / TKA indications login to view 1 more bullet technique login to view 1 more bullet outcomes login to view 4 more bullets metaphyseal osteotomy and plate fixation indications login to view 2 more bullets Prognosis Paget's sarcoma less than 1% will develop malignant Paget's sarcoma (secondary sarcoma) osteosarcoma > fibrosarcoma and chondrosarcoma most common in pelvis, femur, and humerus poor prognosis 5-year survival for metastatic Paget's sarcoma < 10% treatment includes chemotherapy and wide surgical resection