Review of fracture experience during treatment of Paget's disease of bone with etidronate disodium (EHDP)

To evaluate the possible association between fractures among patients with Paget's disease and therapy with etidronate sodium (EHDP), data from large U.S. clinical studies of EHDP were analyzed. The fracture rate for patients who received prolonged therapy with EHDP was not significantly different from that observed in patients who received lower doses of EHDP during a similar period. In addition, the fracture rate was similar to the reported rate for the osteoporotic and the normal aging population, although the types of fractures may be different. When examined as a function of time after initiation of EHDP therapy, the fracture rate was found to decrease with time. When the duration of EHDP therapy and the factors of dose and severity of disease were simultaneously considered, fracture rates were found to be higher among patients receiving high doses of EHDP for long periods. However, it is clear that patients who had higher pretreatment levels of hydroxyproline received the higher doses for longer periods. Also, a joint analysis of the effect of dose regimen and pretreatment disease status showed that pretreatment hydroxyproline was more strongly related to fracture risk than either dose regimen or pretreatment alkaline phosphatase. While the judicious use of EHDP may reduce the risk of fracture, excessive attenuation of bone remodeling and consequent increased fracture risk occurs in some patients treated with higher doses of EHDP for exended periods.