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To the Editor We read with interest the study by Greenspan and colleagues1 that evaluated the clinical benefits of a single dose of intravenous zoledronate (with daily calcium and vitamin D) on bone mineral density and safety for 2 years in frail elderly women in long-term care facilities. This study provides further motivation for patients, clinicians, and researchers to study the optimal dosing interval of increasingly potent bone-targeting agents such as zoledronate and denosumab. It is interesting and perhaps disturbing that, despite the widespread use of these agents for several decades, so few trials have been performed examining optimal dosing intervals. For example, in the setting of cancer therapy–induced bone loss, these agents continue to be given every 6 to 12 months despite data showing that a single injection of zoledronate is associated with prolonged bone density and biomarker response for at least 3 years.2 Similarly, the 3- to 4-week dosing intervals for bone-targeted agent use in metastatic breast and prostate cancers were developed from studies in patients with hypercalcemia and for the convenience of coadministration with standard anticancer agents (eg, chemotherapy). These schedules ignore the long half-life many of these agents have in bone and bone turnover marker studies—a surrogate of skeletal-related event risk—that have consistently shown rapid falls in biomarker levels sustained at significantly lower doses for longer durations than 3 to 4 weeks for both bisphosphonates and denosumab.3
Hutton B, Mazzarello S, Clemons M. Dosing Strategies of Bone-Targeting Agents. JAMA Intern Med. 2015;175(11):1864-1865. doi:10.1001/jamainternmed.2015.4789