The large multicenter HORIZON trial, testing whether IV zoledronic acid, a potent bisphosphonate shown to be very effective in the reducing fracture risk in postmenopausal women with osteoporosis, is as effective as a daily oral bisphosphonate in the prevention and treatment of glucocorticoid-induced OP among men and women with a variety of underlying disases, was recently reported. Designed to show risedronate’s non-inferiority to daily risedronate, this double-blind, double-dummy (all took both IV and pills) RCT, enrolled 833 subjects from 54 international centers. Subjects were randomized to a single dose of zoledronate 5 mg IV or daily oral risedronate 5 mg for 12 months. The trial was divided among 545 subjects who had already received > 3 months of glucocorticoid, who were the “treatment” group and 288 who had shorter duration of glucocorticoid use, called the “ prevention group”. The treatment group was a bit younger (mean age around 53 years), and had more RA, SLE or asthma as the underlying disease, and lower baseline bone density. The prevention group was slightly older (mean age around 57) and more had polymyalgia rheumatica as the underlying disease. 62 subjects dropped out during the trial and the primary endpoint was change in lumbar spine bone density. In both treatment and prevention groups, the zoledronic acid results were at least as good as the risedronate results: as the trial was designed to prove non-inferiority it decidedly did. In fact, the BMD increases with IV therapy at one year were significantly greater. Adverse events were more common in those receiving IV zoledronate, mainly due to transient flu-like symptoms during the 3 days around the time of the infusion. The main caveat is that the daily oral bisphosphonate chosen is not a good comparator as weekly and monthly dosing is much more commonly used. Karen H. Costenbader, MD, MPH