RESUMEN
Leptin is responsible for linking energy metabolism to bone mass. Because astronauts are commonly in negative energy balance during spaceflight, this study was designed to assess individual and combined effects of food restriction and simulated microgravity on bone mass and serum leptin. Six-month-old male Sprague-Dawley rats were randomly assigned to four groups (n = 12 each): two hindlimb-unloading (HU) groups fed 100% (HU100) and 70% (HU70) and two cage-activity control (CC) groups fed 100% (CC100) and 70% (CC70) of their baseline food requirement. After 28 days, CC100 rats gained body weight, whereas all other groups lost body weight; this loss was greater in HU70 than in CC70 and HU100 rats. Serum leptin decreased in CC70 and HU100 (-60% and -27%, respectively) and was not detectable in HU70 animals. Percent osteoid surface in CC70 and HU100 was lower than that of CC100 (7.80%, 8.60% vs. 10.70%, respectively), and this decrease was more pronounced in HU70 animals (4.38%). Mineral apposition rate of CC70, HU100, and HU70 rats was lower than that of CC100 (1.5, 1.6, and 1.5 vs. 2.1 mum/day, respectively). Bone formation rate of CC70, HU100, and HU70 rats was lower than that of CC100 (13.4, 13.1, and 12.2 vs. 40.8 mm(3).mm(-2).day(-1), respectively). The change in bone formation rate was correlated with the change in serum leptin value over 28 days (r(2) = 0.69, P = 0.0007). We conclude that moderate caloric restriction may cause bone loss at susceptible bone sites to a similar degree as does the unloading effect of microgravity; serum leptin may be an important endocrine regulator contributing to this change in skeletal integrity.