Energy restriction reduces bone density and biomechanical properties in aged female rats.

Bone mineral density (BMD) is highly correlated with body weight, and weight loss is associated with reduced BMD. Whether such losses of BMD increase skeletal fragility is unclear. We examined the effect of 9 wk of energy restriction (ER) on bone density, mineral and matrix protein composition and biomechanical properties in mature (20 wk old, n = 12) and aged (48 wk old, n = 16) female rats. Energy-restricted rats were fed 40% less energy than controls that consumed food ad libitum. Bone content of mineral (ash and calcium content) and matrix proteins (hydroxyproline, pyridinium crosslinks and proteoglycans), serum hormones, site-specific bone density and biomechanical properties (peak load, peak torque, shear stiffness and bending stiffness) were measured at the conclusion of the study. In both age groups, ER reduced body weight by 15 +/- 10% (P < 0.001) and dramatically decreased femoral bone density by 32-35% (P < 0.01) compared with controls. Energy restriction resulted in a small reduction in tibia and humerus density, as well as biomechanical properties in the aged but not mature rats (P < 0.05). Reduced serum levels of insulin and estradiol due to ER in aged rats (P < 0.05) may play a role in altering bone quality. These data show that although weight loss due to ER is detrimental to some bone parameters in mature rats, only aged rats show consistent reductions in bone density and biomechanical properties.

Urinary 3H-tetracycline and pyridinium crosslinks differ in their response to calcium restriction in mature and aged rats.

The aim of this study was to evaluate bone resorption (BR) in rats by two methods: chronic 3H-tetracycline labeling (3HTC) and pyridinium crosslink excretion (PYDX), and compare the sensitivity of these markers in two age groups. Female Sprague-Dawley rats at 12-29 weeks of age ("mature", n = 12) and at 40-57 weeks of age ("aged", n = 22) were examined. Skeletal incorporation of 3HTC in aged rats was 43 +/- 8% of that in mature animals (P < 0.01), indicating an age-related decrease in bone turnover. BR was modulated over 9 weeks by calcium restriction (CR), measured by urinary excretion of both 3HTC and PYDX, and compared with age-matched, calcium-adequate controls. At baseline, urinary excretion of 3HTC was not significantly different between age groups, whereas urinary PYDX was 14-20% higher in mature compared with aged rats (P < 0.01). CR produced a 32-39% peak increase in BR (P < 0.01) compared with controls that did not differ significantly between marker or age group. Urinary 3HTC was elevated at weeks 1-3 (P < 0. 01) and reached maximal values at week 2 (32 +/- 17%). Urinary PYDX, however, was not elevated until week 2, reached maximal levels at week 3 (39 +/- 15%), and remained elevated until week 6 (P < 0.01). These data indicate that although both markers are elevated by CR, marker response differs with age, and variability exists for acute and chronic responses.

Fasting and energy intake influence bone turnover in lightweight male rowers.

The purpose of this study was to investigate the influence of an acute 24-hr fast versus usual 24-hr dietary intake on markers of bone turnover in collegiate lightweight male rowers. Bone turnover was measured by serum osteocalcin (OC) and urinary excretion of pyridinium cross-links (pyridinoline [PYD¿ and deoxypyridinoline ¿DPD]). Fasting subjects (F) (n = 14) reduced body weight by 1.7 +/- 0.5 kg but there was no significant change among nonfasting subjects (NF) (n = 13). Following 24 hr of fasting, PYD and DPD were lower in F (14.1 +/- 2.2 and 5.2 +/- 0.7 nmol/mmol creatinine, respectively) compared to NF (16.4 +/- 3.6 and 6.0 +/- 0.8 nmol/mmol creatinine)(p<.05). Fasting also reduce OC levels (4.8 +/- 0.4 ng/ml) compared to NF (6.1 +/- 0.9 ng/ml) (p<.01). Stepwise regression analysis of NF dietary intake indicated that energy intake explained a greater portion of the variation in bone turnover for PYD (34%), DPD (36%), and oseocalcin (46%) compared to other nutrients (p<.05). These results indicate that bone turnover is reduced by 24 hr of fasting and suggest a role for dietary energy intake in regulating bone turnover.

Dietary restriction of energy and calcium alters bone turnover and density in younger and older female rats.

To determine the influence of weight loss with or without adequate calcium intake on bone turnover and density, we examined the influence of dietary restriction of calcium or energy on body weight (BW), bone mineral density (BMD) and bone turnover in both younger (3 mo) and older (10 mo) female rats (n = 66). Diets were designed to allow feeding at two levels of calcium intake (normal = 78 mg/d and low = 15 mg/d) and two levels of energy intake (normal and 40% restriction) while keeping the intake of protein, fat, fiber, vitamins and other minerals equal between groups. Thus rats received either a control diet (CNTL), a diet restricted in calcium, energy or both for 9 wk. Energy restriction reduced BW 5-21% (P < 0.01) and elevated bone formation 10-20% (P < 0.05) in both age groups. Bone resorption was 20-40% above CNTL values (P < 0.05), in rats fed all three restricted diets. In younger rats, BMD increased over time in all groups (P < 0.05), but final BMD was lower in calcium restricted groups compared with CNTL (P < 0.01). In older rats, CNTL had a significantly greater final BMD (P < 0.05) than diet-restricted groups. These data indicate that, in both younger and older rats, dietary restriction of calcium or energy results in an elevated rate of bone turnover. BMD is compromised by calcium restriction in both younger and older rats, whereas only older rats were negatively influenced by dietary energy restriction. Thus the present study indicates a detrimental effect of low-energy diets, as well as inadequate calcium intake, on bone density in mature rats.