Are all bisphosphonates the same? Potential reasons for clinical differences: a perspective.

Bisphosphonates are first-line treatment for postmenopausal osteoporosis and women with low bone mass and risk factors for fracture. These agents are often perceived as having equivalent effectiveness and safety and are even used interchangeably by some practitioners. Research suggests, however, that differences between them are meaningful to the patient and clinician. Data from randomized controlled trials and observational database studies have demonstrated variations between bisphosphonates in the scope of fracture protection, such as vertebral and nonvertebral, as well as the speed of onset of this antifracture effect. It has been proposed that unique properties of each compound related to their mechanisms of action could explain, at least in part, differences observed in clinical outcomes. Although the bisphosphonates share a similar core structure, they also contain two side chains or groups, R1 and R2, attached to the central carbon atom. All bisphosphonates approved by the FDA for postmenopausal osteoporosis contain a hydroxyl side group at position R1, increasing their binding to bone and distinguishing them from earlier bisphosphonates not approved for this clinical use. Differences in the physicochemical and biological properties of the approved bisphosphonates are due to differences in the R2 side group. The presence of nitrogen and its orientation within the R2 side chain can influence each bisphosphonate's overall potency. For the physician to optimally determine the bisphosphonate that best suits an individual patient, it is important that they are aware of the differences between them.