Evaluation of therapeutic efficacy in osteoporosis.

Evaluation of the efficacy of osteoporosis treatments poses a major challenge for clinical investigators. This paper addresses the question of whether increases in bone mass induced by therapy for osteoporosis are sufficient to determine the efficacy of that therapy, or whether long-term fracture endpoint studies are required. Osteoporosis has been defined as a systematic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. This association between bone mass and fracture risk has been found to be stronger than other well-recognized risk factor associations, such as blood pressure and risk of stroke. Although fracture endpoint studies would provide confirmation of the benefit of osteoporosis therapy, such trials require that several thousand patients be studied for many years, making such studies impractical as a means for providing data for the approval of new therapies. Determination of increased bone mass may provide data that are just as useful in evaluating therapeutic efficacy. The use of bone mass as the primary efficacy endpoint for those therapies that are associated with normal bone quality is justified by the well-documented relationship between bone mass and fracture risk observed in several epidemiological studies.