JOURNAL OF BONE AND MINERAL RESEARCH Volume 7, Number 1, 1992 Mary Ann Liebert, Inc., Publishers zyxwvutsrqp Effects of Five Daily 1 h Infusions of Alendronate in Paget’s Disease of Bone D.P. O’DOHERTY,’ B.J. GERTZ,3 W. TINDALE,2 D.G. SCIBERRAS,3 T.T. SURVILL,3 and J.A. KANIS’ ABSTRACT We report a randomized placebo-controlled double-blind study of amino-hydroxybutylidene bisphosphonate (alendronate), infused over zyxwvut 1 h, in 15 patients with Paget’s disease of bone. Alendronate, 10 mg/day for 5 days, suppressed urinary hydroxyproline to 44.9 zyxwvu f 4.8% and serum alkaline phosphatase to 74.6 zy & 5.4% of their pretreatment values within 1 month of the start of treatment. Within 5 months of the start of treat- ment serum alkaline phosphatase fell to 47.9 & 6.3% of pretreatment values. These effects were associated with a decrease in serum calcium and phosphate and in urinary calcium excretion and with a rise in serum iPTH values. A transient fever was observed in 3 of 10 patients who received alendronate during the course of the infusions, and this was associated with a decrease in the total and differential white cell count. No ad- verse effects were noted on renal function as judged by glomerular filtration rate and indices of proximal and distal tubular function. This regimen may simplify the management of patients with Paget’s disease of bone. INTRODUCTION HE USE OF BISPHOSPHONATES in the treatment of dis- T orders associated with increased resorption of bone is now well established. Because of the low and variable ab- sorption of oral preparations, the intravenous route of administration has been popularized. (I-.) High doses of bisphosphonate can be administered by this route over rel- atively short periods, usually as a series of infusions over several days. Infusions are commonly administered over 2-4 h because of concerns over the nephrotoxicity of bis- phosphonates when they are administered rapidly. (5) Renal damage has been reported in dogs after bolus injections of bisphosphonate,(6) and there are isolated reports of renal failure in patients receiving bisphosphonates for hypercal- cemia of which may have been related to their rapid infusion.(’) Aminohydroxybutylidine bisphosphonate (alendronate) is a potent new bisphosphonate that has recently become available for clinical testing. In Paget’s disease doses up to zy 5 mg/day have been administered over 2-4 h with no ap- parent adverse effect on renal function.(8’ The aims of this study were to examine the safety of similar doses given over a shorter period, with particular emphasis on renal function. PATIENTS AND METHODS A group of 15 patients with active Paget’s disease of bone were randomized prospectively to receive 5 days of treatment with either alendronate (10 mg/day) or placebo under double-blind conditions. Of the 15, 10 patients (6 males and 4 females, mean age 69.2 f 2.5 years) received alendronate, and 5 patients (3 males and 2 females, mean age 64.8 f 2.7 years) received placebo. The diagnosis of Paget’s disease was established by the finding of hyper- phosphatasia and characteristic radiographic and scinti- graphic features. In each case the drug (alendronate or pla- ‘WHO Collaborating Centre for Metabolic Bone Diseases, Department of Human Metabolism and Clinical Biochemistry, University ’Department of Nuclear Medicine, University of Sheffield Medical School, UK. ’Merck, Sharp and Dohrne Research Laboratories, Woodbridge, NJ, and Harlow, UK. of Sheffield Medical School, UK. 81