Age-related bone loss in mice is associated with an increased osteoclast progenitor pool

Age-associated osteopenia has been documented to occur in mice and, therefore, provides a model system whereby mechanisms of bone loss can be assessed in vivo and in vitro. One such mechanism, that could explain the increased resorptive activity seen in some forms of osteopenia, is an age-associated increase in the osteoclast precursor pool and osteoclastogenic formation. To test this hypothesis, we studied the bone marrow composition of aged (24 months) mice to determine if increased numbers of monocyte/macrophage/osteoclast precursor cells (MMOPC) were present when compared to young (4-6 months) animals. Our data show a moderate increase of 20-30% more hematopoietic cells obtained from the long bones of the aged animals. However, both liquid and semi-solid culture techniques demonstrate an approximately 2-3.5-fold increase in the numbers of plastic adherent macrophages or mononuclear colonies in bone marrow derived from the aged mice when stimulated by interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) or macrophage colony stimulating factor (GM-CSF), indicating a preferential increase in MMOPCs. In addition, cells derived from the aged mice show higher levels of cytokine stimulated incorporation of [3H]-thymidine and [3H]-leucine, with increased protein synthesis seen up to 7 days after cytokine stimulation, suggesting that these cells also have an enhanced sensitivity to cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)