AbstractAimHigh body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole‐body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight.MethodsWe recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co‐twins 7.6 kg/m²; eight female pairs). Ten pairs completed the 6‐month long training intervention. We measured lumbar vertebral and femoral BM insulin‐stimulated glucose uptake (GU) using ¹⁸F‐FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers.ResultsAt baseline, heavier co‐twins had higher lumbar vertebral BM GU (p < .001) and lower bone turnover markers (all p < .01) compared with leaner co‐twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole‐body insulin sensitivity, aerobic capacity (both p < .05) and femoral BM GU (p = .008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p = .02), as GU tended to decrease in heavier co‐twins (p = .06) while there was no change in leaner co‐twins.ConclusionsIn this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co‐twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity.