Age-related osteopenia: evidence for an intrinsic defect of bone resorbing cells and a possible treatment

B6D2F1 and B6AF1 mice of various ages were given sublethal or lethal doses of X radiation and injected with marrow and/or spleen cells from young, mature, or old syngeneic donors. Four to five months later they were killed and ash weights were determined on femurs, sacrum, and ilium. It was found that large numbers of marrow cells (i.e., greater than 25 X 10(6] and/or spleen cells (greater than 50 X 10(6] from old mice retarded the growth of bone in young hosts and induce loss of bone mass in mature recipients, spleen cells from young donors consistently prevented the loss of bone mass normally seen in aging mice, and the thymus and T cells did not appear to play a significant role in bone resorption and remodeling. These observations suggested that in aging mice loss of bone mass is caused by an intrinsic defect in a hematopoietic cell population, perhaps the macrophage/osteoclast or their common precursor, which results directly or indirectly in increased bone resorption. On this basis, promethazine HCl, an inhibitor of macrophage metabolism and phagocytosis, was added to the drinking water (1.0 to 4.0 mg/dl) of aging mice. Four to five months later it was found that bone mass was significantly greater in the groups given promethazine than in the age and weight matched controls.