Paget’s disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal increases in disorganized bone remodelling which disrupt normal bone architecture, causing the affected bones to enlarge and become weakened. This can lead to various complications including pain, deformity, fracture, nerve compression syndromes, and osteoarthritis. Genetic factors play a key role in the pathogenesis of PDB. This is mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which have additive effects on disease susceptibility. Suggested environmental factors for PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are a more sensitive method of defining disease extent. Serum total alkaline phosphatase levels are usually raised in patients with metabolically active disease and are often used as a measure of disease activity. Bisphosphonates are the treatment of choice for PDB; they reduce the elevations in bone turnover that are characteristic of the disease and are an effective treatment for bone pain. Among the bisphosphonates, zoledronic acid is most likely to give a favourable pain response. Bisphosphonate treatment should not be given with the primary aim of normalizing elevated biochemical markers of bone turnover since there is no evidence that this is beneficial. Although potent bisphosphonates can normalize elevated bone turnover in many patients with PDB, it unclear as yet whether this prevents complications of the disease.
