The diphosphonates are currently the skeletal imaging agents of choice and while extremely sensitive for bony abnormality their mechanism of action remains poorly understood. The current concepts in bone uptake mechanisms are reviewed and it is concluded that diphosphonate uptake is most likely related to sites of newly forming bone with diphosphonate adsorbed onto the surface of hydroxyapatite crystals. In situations where there is markedly increased skeletal uptake of tracer, increased vascularity alone cannot account for changes in tracer uptake and changes in skeletal extraction, related to newly forming bone are more important.
