Diphosphonates inhibit human osteoblast secretion and proliferation.

In view of the beneficial effect of diphosphonates in Paget's disease and their suppressive effect on alkaline phosphatase, the action of three diphosphonates (aminohydroxypropylidene diphosphonate [APD], clodronate, and didronel) on cultured human osteoblasts in vitro was investigated. All three inhibited basal and 1,25(OH)2 cholecalciferol-stimulated alkaline phosphatase secretion and [3H]thymidine uptake by osteoblasts. It is concluded that diphosphonates consistently inhibit human osteoblasts through a direct action in addition to their known effect on inhibiting bone resorption and that these actions together may form the basis of their beneficial effect in vivo in patients with Paget's disease.