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Ralston, Stuart H. (2024). In Goldman-Cecil Medicine (pp. 1665). DOI: 10.1016/B978-0-323-93038-3.00228-8
Bisphosphonates can cause kidney injury and are contraindicated in patients with significant renal impairment.Other Drug TreatmentsAnalgesics, nonsteroidal anti-inflammatory drugs (seeTable 26-4), and antineuropathic agents (e.g., amitriptyline 10 to 25mg at bedtime or gabapentin 300mg three times daily; seeTable 26-5) may be required in patients with Paget disease, particularly when osteoarthritis or a nerve compression syndrome coexists. Calcitonin, 50 to 100 IU subcutaneously three times a week for up to 3 months can improve bone pain due to metabolic activity in Paget disease but is seldom used except in patients for whom bisphosphonates are contraindicated; adverse effects such as nausea and flushing can be problematic, and resistance may develop owing to the formation of neutralizing antibodies.Nonpharmacologic TreatmentsNonpharmacologic approaches (e.g., acupuncture, physiotherapy, hydrotherapy, and transcutaneous electrical nerve stimulation) are often used to control pain, but their effectiveness has not been documented in controlled trials. Clinical experience suggests that specific problems such as limb shortening and deformity can be helped by aids and devices such as walking sticks and shoe raises.Monitoring Disease Activity and the Effects of TreatmentMetabolic activity and the response to treatment are typically assessed by measuring the alkaline phosphatase level, but levels can be normal in patients with localized disease that is metabolically active. Further courses of treatment should be considered in patients who have recurrent or persistent pain and in whom alkaline phosphatase levels remain or become elevated.SurgeryOrthopedic surgery may be required for the management of coexisting osteoarthritis, pseudofractures, fractures, bone deformity, and spinal stenosis. Osteotomy is performed infrequently, but small case series have reported good results.
The most common indication for medical treatment of Paget disease is bone pain localized to an affected site.Bone pain may be caused by increased metabolic activity, but other causes may be operative, such as nerve compression syndromes, pseudofractures, secondary osteoarthritis, and other musculoskeletal conditions. Careful assessment of the patient is therefore necessary to decide on the most appropriate treatment. Bone pain caused by increased metabolic activity is localized to the affected site and is usually accompanied by a raised alkaline phosphatase level. It is common to encounter patients in whom pain occurs in the presence of coexisting osteoarthritis, bone deformity, or other musculoskeletal conditions. In such cases, it can be difficult to be sure about the origin of the pain, and many clinicians give a therapeutic trial of bisphosphonates to aid diagnosis. If the pain responds, it is assumed to be due to increased metabolic activity; if it does not, further evaluation should be undertaken to identify the cause and treat the patient appropriately. Pseudofractures, which are areas of focal osteolysis that traverse the lateral cortex of weight-bearing bones of the lower limbs, represent a distinct management problem. Some remain stable for prolonged periods without causing symptoms; others regress spontaneously; and others progress to pathologic fracture, often in association with a localized increase in pain at the affected site.BisphosphonatesBisphosphonates are the drugs of first choice for the treatment of pain that is thought to be due to increased metabolic activity, and strong evidence indicates that they are more effective than placebo at improving bone pain in Paget disease (Table 228-1).Data comparing different bisphosphonates are limited, but intravenous zoledronic acid has been found to be superior to pamidronate and risedronate for lowering alkaline phosphatase leveland for relieving pain.Repeated courses of bisphosphonates with the aim of normalizing alkaline phosphatase (intensive treatment) is no better in terms of pain, quality of life, or complications compared with therapy primarily aimed at controlling symptoms (symptomatic therapy).
