Summary We carried out a cross-section study of the sexspecific relationship between bone mineral content and physical activity at sites with different loading in pre-and early pubertal girls and boys. There was significant sensitivity of bone mineral content of the hip to physical exercise in boys, but not in girls. Background Since little is known whether there are sex differences in sensitivity of bone to loading, we investigated sex differences in the cross-sectional association between measures of physical activity (PA) and bone mass and size in pre-and early pubertal children of both sexes.Methods We measured bone mineral content/density (BMC/BMD) and fat-free mass (FFM) in 269 6-to 13-year-old children from randomly selected schools by dualenergy X-ray absorptiometry. Physical activity (PA) was measured by accelerometers and lower extremity strength by a jump-and-reach test. Results Boys (n=128) had higher hip and total body BMC and BMD, higher FFM, higher muscle strength and were more physically active than girls (n=141). Total hip BMC was positively associated with time spent in total and vigorous PA in boys (r=0.20-0.33, p<0.01), but not in girls (r=0.02-0.04, p = ns), even after adjusting for FFM and strength. While boys and girls in the lowest tertile of vigorous PA (22 min/day) did not differ in hip BMC (15.62 vs 15.52 g), boys in the highest tertile (72 min/day) had significantly higher values than the corresponding girls (16.84 vs 15.71 g, p<0.05). Conclusions Sex differences in BMC during pre-and early puberty may be related to a different sensitivity of bone to physical loading, irrespective of muscle mass.