Alternative bisphosphonate targets and mechanisms of action.

As the number of bisphosphonates continues to increase, they have found widespread use in an increasing number of clinical conditions. Ongoing examination of their targets and mechanisms of action has revealed that this surprisingly diverse class of drugs has effects beyond those first described for osteoclasts. These additional targets include osteoblasts, osteocytes, angiogenesis, and gammadelta T lymphocytes of the human immune system. The immune system effects are specifically targeted to gammadelta T cells and are reminiscent of the effects seen after ingestion of tea beverage. BP effects on such alternate targets may explain not only their antiresorptive effect, but also their effect on bone quality, tumors, and microbes.