Restriction of dietary energy intake has a greater impact on bone integrity than does restriction of calcium in exercising female rats.

We sought to elucidate the effects of restricting calcium, energy, or food on the skeletal integrity of exercising female rats. Female Sprague-Dawley rats (4 mo old) were randomly assigned to 5 groups (n = 10/group): ad libitum intake of an AIN-93M diet (Research Diets D10012M, Research Diets, Inc.) with no exercise (AL-S) or with exercise (AL-EX) or to 1 of 3 exercising restriction groups [40% restriction of calcium only (CAR-EX), energy only (ER-EX), or food (FR-EX)]. All EX rats were treadmill trained 3 d/wk, 45 min/d for 12 wk at ~60% maximal oxygen consumption. After 12 wk, total body bone mineral content (by DXA) and body mass, but not lean mass, were lower in ER-EX (-17%) and FR-EX rats (-13%) compared with the AL-EX group. CAR-EX had few negative effects on bone geometry (by peripheral quantitative computed tomography) or histomorphometry. However, declines in total volumetric bone mineral density at the proximal tibia metaphysic (PTM) were observed in ER-EX (-6%) and FR-EX (-8%) groups; only FR-EX rats exhibited increased osteoclast surface and decreased mineral apposition rate in PTM cancellous bone. Decrements in serum estradiol, uterine weights, or both in these 2 groups implicate altered estrogen status as contributory. Urine pH declined significantly by 12 wk in all restricted groups, but net acid excretion increased only in CAR-EX rats. These findings, when compared with published data on sedentary rats, suggest that treadmill running exercise may mitigate some, but not all, deleterious effects on bone after chronic energy or food restriction but is more protective during calcium restriction.