Page 74 - Retail Pharmacy Magazine October 2020

72 CPD ACTIVITY FROM PAGE 71 symptom. The disease appears to arise more or less simultaneously in one or more skeletal sites and remains restricted to these sites.3 Some ways in which Paget disease may present include:2,3,4,5 • Bone pain, which can range from minimal bony discomfort to severe pain in long bones due to pathological fractures. Distinguishing between bone pain due to Paget disease and joint pain due to associated arthritis can be difficult, but bone pain due to Paget disease is typically worse at rest (often at night or early after rising) and is relieved by movement, whereas pain from osteoarthritis secondary to Paget disease tends to be worse with movement. • Persistently aching legs caused by defects in the tibia and fibula causing tibial bowing. • Increased localised temperature over areas of active disease. • Chronic hip and thigh pain. • Hearing loss due to enlarged bones causing nerve compression. • Bony deformities, eg, frontal bossing of the skull bones. • Spinal canal stenosis due to narrowing of the spinal canal and paraplegia. • Loose teeth and associated chronic facial pain due to enlarged facial bones. • Excessive blood loss should orthopaedic surgery be required due to increased vascularity of bone. • Osteoarthritis in joints adjacent to deformed bones, a common complication of Paget disease. • Osteosarcoma, a rare complication. Diagnosis Serum total alkaline phosphatase (ALP), performed as part of liver function tests in a biochemistry screen, is a marker of bone turnover and is recommended as the first- line biochemical screening test for Paget disease.1 A serum total ALP above 125 units/lt in the absence of another cause (eg, liver function abnormality, vitamin D deficiency, hyperparathyroidism) suggests active Paget disease1. X-rays of the abdomen, skull, facial bones and both tibias are recommended as a method to identify lesions at these sites and will detect 93 per cent of Paget lesions compared with 79 per cent for an abdominal X-ray alone5. The characteristic X-ray features of Paget disease are bone expansion, cortical thickening, trabecular thickening, bone deformity, osteolytic areas and osteosclerosis.5 Individually, these features are not specific, but when they occur in combination, they are usually diagnostic.5 In long bones, the disease first appears in the region of the proximal epiphysis and advances along the shaft at a rate of about 8mm a year. The leading edge of this advance is often visible as a V-shaped ‘lytic wedge’ reflecting osteoclastic resorption.3 Radionuclide bone scans are recommended as a means of fully and accurately defining the extent of disease, rather than for diagnosis.1 Management Bisphosphonates are the treatment of choice for symptomatic Paget disease to relieve symptoms and to prevent complications1. Analgesics and NSAIDs can also be used as supportive treatments to ease symptoms related to bone pain and secondary osteoarthritis.1 Treatment is not recommended for asymptomatic Paget disease as there is no evidence that bisphosphonates prevent bony deformities in this group. However, treatment is indicated for asymptomatic patients at risk of complications. This includes patients who are young (aged under 50), those with active disease in an area of the skeleton that is considered high risk for complications (eg, the facial bones, skull, adjacent to a joint), those with hypercalcemia, neurological symptoms and those requiring orthopaedic surgery of or near a pagetic bone.1 Bisphosphonates Bisphosphonates inhibit bone resorption by inhibiting excessive osteoclast activity.6 They reduce bone turnover, improve bone pain and promote healing of osteolytic lesions.2 Intravenous zoledronic acid is the most effective bisphosphonate for Paget disease. The vast majority of patients achieve sustained remission following a single dose of zoledronic acid.1 Dosing is as follows:1 Zoledronic acid 5mg by intravenous infusion over at least 15 minutes. If zoledronic acid is not appropriate, the following alternative bisphosphonates can be used:1 Risedronate 30mg orally, daily on an empty stomach, for two months. OR Pamidronate 60mg by intravenous infusion over four hours. If the serum total ALP remains elevated after three months, or if the patient still has symptoms, a repeat course of risedronate or pamidronate may be considered after six to 12 months.1 A clinical trial showed that zoledronic acid given as a single 5mg dose intravenously was more effective than risedronate 30mg daily orally for two months in improving biochemical markers and providing pain relief. At six months, 96 per cent of patients receiving zoledronic acid had a therapeutic response compared with 74.3 per cent of patients receiving risedronate.7 An extension of the same study showed that, at 6.5 years, clinical relapse occurred in 0.7 per cent of patients in the zoledronic acid group compared with 20 per cent of patients in the risedronate group.8 Precautions and adverse effects with bisphosphonates • Patients should be well hydrated before receiving zoledronic acid. They should be advised to drink at least two glasses of water before and after the infusion.6 The CrCl should be greater than 35ml/minute.6 • Calcium and vitamin D levels should be normal prior to treatment to prevent hypocalcemia. Calcium supplementation should be given for at least 10 days following zoledronic acid dose.6 • Fever and flu-like symptoms in the days following zoledronic acid infusion are common, occurring in about 30 per cent of people receiving zoledronic acid for the first time.9 Paracetamol may be taken to ease symptoms. • Oesophagitis and gastritis may occur with risedronate. The tablet should be swallowed whole with a full glass of water at least 30 minutes before food or drink. Patients must remain upright for 30 minutes after taking the tablet. They should be advised to see their doctor immediately if they have pain on swallowing or new or worsening heartburn.6 • Osteonecrosis of the jaw is a rare complication with some dental procedures. Risk is related to potency, route and total dose of bisphosphonate. Most reports have followed the use of IV zoledronic acid or pamidronate in patients with multiple myeloma or bony metastases. A full dental assessment and completion of any dental work should be considered before starting treatment.6 RETAIL PHARMACY • OCT 2020