Page 73 - Retail Pharmacy Magazine October 2020

CPD ACTIVITY 71 PAGET DISEASE OF BONE Morna Falkland Morna is a medicines information pharmacist who has worked in the hospital sphere in Canberra. LEARNING OBJECTIVES After completing this CPD activity, pharmacists should be able to: • Describe the cause and symptoms of Paget disease of bone. • Describe the diagnosis and monitoring of Paget disease of bone. • Outline the treatment for Paget disease of bone. 2016 Competency Standards: 3.1, 3.2. Accreditation Number: A2010RP2 (Exp. 30/09/2022). Introduction Paget disease of bone is a disorder of bone metabolism characterised by focal areas of excessive bone resorption by osteoclasts and disorganised formation by osteoblasts, resulting in abnormal bone remodelling.1 Bones in one or more parts of the skeleton become deformed, causing bone pain, bony deformities, neurological syndromes, osteoarthritis and arthropathies. The most common areas affected are the pelvis, lumbar spine, skull, femur and tibia.2 The disease is named after British surgeon James Paget, who first described it in 1877.2 The prevalence of Paget disease increases with age and presents mainly in middle-aged or older adults. It affects around two to four per cent of people aged over 55 in certain countries.1 The greatest prevalence occurs in north- western England. It’s also common in western Europe, the US, Australia and New Zealand. It’s rare in Scandinavian countries, the Indian subcontinent and other Asian countries.2,3. Pathophysiology The primary abnormality of Paget disease of bone is believed to be in the osteoclasts, which are abnormally large and have excess nuclei. During the lytic phase of the disease process, an increase in osteoclast activity triggers excessive bone resorption. This is followed by a compensatory, rapid increase in the numbers of osteoblasts, resulting in disorganised bone formation. A high bone remodelling rate, at six to seven times higher than normal, results in bone that is enlarged, mechanically weak and subject to deformity and fracture.2,3 Having reached its maximal extent and activity, the disease then appears to remain more or less stable for many years with relatively small fluctuations in bone turnover markers.3 The pathogenesis of Paget disease is incompletely understood, but both genetic and environmental factors are involved. Many people with the disease have a family history, and it can be inherited in an autosomal dominant pattern with incomplete penetrance.1,2 The relative risk of developing the condition is as high as seven in first-degree relatives of people diagnosed with Paget disease4. The most important susceptibility gene for Paget disease is SQSMT1.2,3,4 Recent studies have identified a further seven susceptibility genes for Paget disease.4 Evidence for the influence of environmental factors playing a role in Paget disease is shown by the fact that the incidence has steadily reduced over the past 30 years, particularly in regions that previously had a high prevalence.5 The exact environmental cause of Paget disease is unknown but suggested triggers include paramyxoviruses such as measles virus and canine distemper virus. Evidence of measles virus nucleocapsid protein in pagetic osteoclasts has led to a model proposing that a virus might interact with genetic factors to produce the disease.4 However, some groups have been unable to replicate this finding. A decline in prevalence of Paget disease following introduction of the measles vaccine may lend credence to this theory, although it appears the decline may have begun before this time.4 Local trauma to bone and exposure to environmental toxins such as arsenic have also been proposed, but the exact environmental agent remains unknown.4,5 Symptoms Most people with Paget disease are asymptomatic.2,4 The disease is detected most frequently as an incidental finding on imaging conducted for another disorder or on biochemistry. It has been estimated that fewer than 10 per cent of patients with X-ray evidence of Paget disease come to medical attention.5 In those that do present clinically, bone pain is the most common TO PAGE 72 RETAIL PHARMACY • OCT 2020 2 CPD CREDITS