Paget's disease of bone. An update on management

The essential requirement for effective treatment of Paget's disease of bone is that the characteristic abnormality of bone remodelling is predictably corrected without the occurrence of significant side effects. Although the ideal agent is not currently available, appropriate use of the calcitonins or diphosphonates goes a long way to achieving this goal. Calcitonin (50 to 100 MRC units subcutaneously daily or 3 times weekly) will generally reduce bone turnover by approximately 50% within 6 months. However, very active disease will not be controlled and bone turnover will generally increase once treatment is withdrawn. Calcitonin is without significant side effects, although some patients will develop antibody-mediated resistance to the exogenous calcitonin species. An advantage of calcitonin is that there is radiographic evidence of a return to normal bone remodeling during treatment. Although a number of diphosphonates (now more correctly termed bisphosphonates) are available for experimental use, only the first generation compound, disodium etidronate (EHDP) is commercially available. It too will reduce bone turnover by about 50% within 6 months when given in a dose of 5 mg/kg daily. Unlike calcitonin, it results in a more sustained control of bone turnover while having the additional advantage that it can be given by mouth. Although larger doses are more effective in controlling very active disease, there is a real risk of causing defective bone mineralisation which may result in the development of atraumatic long bone fractures or diffuse bone pains. Combinations of calcitonin and disodium etidronate in conventional dosage seem to result in an additive suppressant effect on bone turnover and may be indicated for more active disease. Advances in treatment are progressing rapidly and it seems likely that in the next few years the introduction of new agents for the control of Paget's disease will more nearly approach the ideal goal of treatment.