Bone mineral density and biochemical markers of bone turnover are useful endpoints in Phase II dose-ranging trials and other studies aimed primarily at internal decision making. The advantage of these endpoints is that they allow for shorter trials with fewer subjects. However the validity of bone mineral density and biochemical markers as surrogates for fracture in clinical trials is not yet established. Thus therapeutic confirmatory studies require fracture as an endpoint. Various fracture endpoints have been employed including morphometric vertebral fracture, hip fracture and all clinical fractures.

Recognizing the wide variability in the quality of acquisition and standards for interpretation of densitometry scans and spinal radiographs, U.S. and European regulatory agencies recommend the use of central facilities for the management and reading of these data. Moreover, because of the importance of equipment performance in quantitative measures of bone mineral density, steps to ensure the accuracy and stability of the densitometers used in a trial are warranted.