IKE II~ MATOPOIESIS, bone remodeling requires the con-L tinual production of relatively short-lived cells, and for both processes manipulation of cell production is more important than manipulation of differentiated cell function, and regulates supply in relation to demand.'" In the adult skeleton, the demand for osteoblasts is created by bone resorption, but the demand for osteoclasts is governed by the purposes of bone remodeling. Most therapeutic agents used for the prevention and treatment of osteoporosis are referred to as inhibitors of bone resorption, but this vague term obscures the important distinction between inhibition of the recruitment of new osteoclasts and inhibition of the function of existing osteoclasts.'" Although bisphosphonates as a class have been studied for more than 25 years, their mode of action as inhibitors of bone resorption is still unclear and is probably different for different members of the class.'" In the intact organism, tetracycline-based histomorphometric studies indicate a major long-term effect of bisphosphonate administration to reduce the rate at which new cycles of bone remodeling are initiated, or activation frequency,(4,') an expression of reduced osteoclast recruitment and the basis for the reduction in whole body bone turnover shown by biochemical But in vitro studies have demonstrated powerful inhibitory effects of bisphosphonates on the function of existing os-teoclasts'3. x-"''with minor or conflicting effects on osteoc I ast recruit men t.'-3,'I.')