Influence of fracture criteria on the outcome of a randomized trial of therapy

Based on a presumption that the morphometric approach to vertebral fracture assessment is beset by false positive deformities, it has been suggested t hat more stringent criteria should be used to assess vertebral fracture out comes in clinical trials of osteoporosis therapies. We applied a variety of criteria in the reanalysis of a randomized trial of sodium fluoride therap y for women with established osteoporosis. Although progressively more seve re criteria reduced the cumulative incidence of a new vertebral fracture in both those receiving a placebo and the fluoride-treated patients, differen ces between the two groups were not magnified and none of the suggested app roaches produced a statistically significant result. These findings indicat e that the false positive rate associated with morphometric assessment of v ertebral fractures is not so great as supposed from theoretical considerati ons that assume independence among the measurements. Our findings also prov ide some reassurance that differences in the criteria used to define a vert ebral fracture are not the controlling influence in the likelihood that a p articular clinical trial will find a result favoring one treatment over ano ther.