Stem cell antigen-1 (Sca-1/Ly6A) is a GPI-AP expressed by a variety of stem cell populations. Previous studies involving Sca-1 knockout (KO) mice revealed an age-related osteoporotic phenotype, characterized by decreased bone mass and bone brittleness, due to mesenchymal progenitor defects. In this study, the in vitro mesenchymal progenitor cell phenotype of Sca-1-/- mice and wild type BALB/ c controls was characterized at 3, 5, 7, 9 and 12 months of age. A significant defect in osteo-, adipo- and total mesenchymal progenitors in Sca-1-/- mice was found to arise between 5 and 7 months of age, as measured by the CFU-A, CFU-ALP/O, and CFU-F assays, persisting until at least 12 months. These defects encompass progenitor self-renewal, expansion, and potentially osteogenic and adipogenic differentiation. These results provide the baseline parameters enabling the use of Sca-1-/- mice in future studies as model of age-related osteoporosis.