The effect of partial gravity (G) (as on the Lunar surface) on weight bearing bone remains undefined; a new model (the partial G mouse) provides for graded reductions in weight bearing. We hypothesized that mice exposed to 1/6th G and 1/3rd G will experience significant reductions in cancellous bone mass and altered microarchitecture as compared to ambulatory control animals but that the magnitude of these changes would be less than in 0 G mice.MethodsForty‐three female BALB/cByJ mice were randomly assigned to cage control (1G), “zero‐gravity” hindlimb unloaded (0G), 1/6th gravity (G/6), or 1/3rd gravity (G/3) groups for a 21‐day suspension protocol. In vivo peripheral quantitative computed tomography (pQCT) scans were conducted at the proximal tibia metaphysis on days 0 and 21 to measure volumetric bone mineral density (vBMD). Ex vivo micro‐CT scans were conducted at the distal femur to quantify bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N).ResultsBody mass decreased significantly (7.6%) in 0G mice and non‐significantly in the G/3 or G/6 groups (−3.9%). In vivo total vBMD at the proximal tibia decreased significantly in the 0G (20%), G/6 (14%), and G/3 (14%) groups compared to 1G mice (−3%). Relative to the 1G group, distal femur BV/TV, Tb.Th, and Tb.N in the 0G, G/6 and G/3 groups were lower (24%, 12%, 14%, respectively). Mineral density gray scale of distal femur cancellous bone was significantly lower only in 0G (−2.6%) vs. 1G mice.ConclusionThese data suggest that partial weight bearing (as high as 1/3rd G) does not provide enough mechanical loading to prevent the significant deterioration of cancellous bone observed in the 0G non‐weight bearing condition. Funded by NSBRI via NASA Cooperative Agreement NCC 9‐58.