NGF and neoplasm: Once the new nerve is established, osteoclast inhibition is less likely to modulate pain and this might explain why bisphosphonate trials in human OA seem to have at best a modest effect on symptoms and no effect on structural outcomes.95,106 NGF is possibly the directional cue for these new nerves, as has been demonstrated in tumours,41 and once formed it is also acts to sensitise them, thus explaining rapid clinical success in anti-NGF trials.