21st July 2023

Paget’s Disease

This is a disease of disordered bone remodelling in a localised area due to increased osteoclastic activity. This results in increased and uncontrolled bone turnover and a subsequent increase in osteoblast activity as a compensatory mechanism. Risk factors include old age, European ethnicity, and a family history of Paget’s disease.

Paget’s disease is often asymptomatic but can present with bone pain or pathological fractures. It usually affects the lower limb’s skull, vertebral column, pelvis, and long bones. As the disease progresses, it can present with osteoarthritis (if it occurs near a joint), deafness (due to nerve compression), radiculopathy, osteosarcoma, bone thickening and deformity and cardiac failure.

Blood tests show an isolated raised alkaline phosphatase (ALP) with normal calcium and phosphate levels. In specialist settings, other bone turnover markers can be assessed. These include serum procollagen type I N-terminal propeptide (P1NP), serum C-telopeptide (CTx), urinary N-telopeptide and urinary hydroxyproline (NTx). X-rays show lytic lesions at the early stages. As the disease progresses, mixed lytic and sclerotic lesions are found. In the later stages, X-rays may show cortical or trabeculae thickening, which can present as localised bone enlargement radiologically. Pseudo fractures can also sometimes be seen in long bones. Bone scintigraphy is more sensitive than plain x-rays and can show active areas of Paget’s disease. This is particularly useful in early disease.

Treatment is commenced for patients experiencing bone pain, deformity, or pathological fracture. Bisphosphonates are initially used (oral alendronate or risedronate). If there is no response, intravenous zoledronic acid may be considered. Treatment length depends on clinical response (patient’s symptoms) and biochemical response (suppression of ALP).

Treatment is rarely indicated in asymptomatic patients. In some cases, treatment may be considered if there are significantly active lesions in areas that could lead to future complications, e.g., near the joints or risk of nerve impingement.