Combination therapy for osteoporosis: considerations and controversy.

Combination therapy, the simultaneous use of two pharmaceutical agents with the goal being reduction of fracture risk, is an area of substantial clinical interest. This paper summarizes the rationale, existing clinical trials data, and other considerations relevant to combination therapy for osteoporosis. Combinations of antiresorbers (eg, estrogen plus bisphosphonates) produce greater increases in bone mass than either treatment alone. Conversely, combining anabolic agents (parathyroid hormone) with bisphosphonates does not produce additive effects. None of the existing studies are large enough to determine whether combination treatment reduces fracture risk to a greater extent than use of a single agent. However, it is certain that combination treatment will increase cost and likely that it will increase side effects and reduce therapy adherence. Given the absence of demonstrated fracture reduction benefit, increased cost and likely increase in adverse events, combination therapy is not currently recommended.