The stumble-from pipe cleaner to bone builder.

Objective: To review the history of the transition of bisphosphonate use from bench chemistry to clinical applications.

Methods: Pertinent medical literature, including limited-distribution as well as peer-reviewed publications, was reviewed.

Results: Bisphosphonates were originally developed to interfere with calcium deposition. An expanded understanding of bone physiology, as well as a growing appreciation of bisphosphonate chemistry, allowed a broadening range of clinical applications.

Conclusion: The use of bisphosphonates in clinical medicine depended on a series of fortuitous events that, at the time, were "stumbles," not unlike the discoveries of Fleming and Newton. The logical sequence is more apparent in retrospect.