Faculty Bibliography

The influence of physical activity on bone formation and resorption was studied in the following three groups of 6-wk-old female rats: 30 controls, 24 sciatic denervation immobilized, and 28 treadmill exercised. Bone formation and resorption were determined from 45Ca retention, 45Ca excretion, bone calcium content, bone volume, and resorbing surface and bone formation rate assessed by tetracycline labeling. 45Ca (30 microCi) was administered intravenously to each animal before study, and the excretion of isotope in the urine and feces was then determined during the 6-wk experimental period. Exercise resulted in an initial increase in total excretion of 45Ca (P < 0.01) followed by a drop to below control levels (P < 0.001). The femoral 45Ca retention and calcium content of the exercised group were higher than that of the control group at week 6. Periosteal bone formation rate in the tibia was enhanced during days 32-41 (P < 0.01). With immobilization, the weekly excretion of 45Ca was persistently higher (P < 0.01), and the femoral 45Ca retention (P < 0.05) and calcium content (P < 0.01) were lower than the control group. Periosteal and endosteal bone formation rates were lower than in the controls over the first 31 days. In conclusion, exercise in young growing rats is associated with an initial increase and then a decrease in bone resorption while active bone formation is sustained. Immobilization for 6 wk results in an increase in bone resorption and a rapid fall in bone formation.

One-hundred thirty-six women with spontaneous vertebral crush fractures had bone density measurements by photon absorptiometry. Their absolute and relative extent of osteopenia were expressed as Z scores with respect to values from normal white women. Absolute Z scores were used to express the mean bone mass of women with crush fractures vis-a-vis normal women at peak bone mass; relative Z scores were used to express the same means vis-a-vis age-matched controls. The skeletal sites measured included the distal radius, lumbar spine, and three sites on the femur (neck, Ward's triangle, and trochanter). The absolute deficit for the five sites ranged from -1.66 to -2.60. The relative deficit was close to 1 SD for all sites. A discriminant analysis revealed that the spine and femur were predictive for vertebral crush fractures but the radius was not. Comparison with a previously reported hip-fracture population (n = 31) showed that the low bone density of the spine separated the two fracture groups best. We propose the following: (a) vertebral-fracture patients have extensive generalized osteoporosis including the hip with a preferential deficit in the spine and (b) hip-fracture patients have generalized osteoporosis with preferential osteopenia of the hip and do not have a greater mineral deficit in the spine or radius than age-matched normal women. It may be that if a single site is to be selected for screening for spine and hip fractures, the greatest value would be in measurement of the femur, although ideally the skeletal site of interest would be measured. Prospective studies are needed to confirm the utility of measurements at the spine and hip in prediction of future fractures.

Bone density was measured in 31 white women with hip fractures by single- and dual-photon absorptiometry at the radius, lumbar spine and proximal femur. The mean age was 71.4 years. Comparison with premenopausal normals revealed Z-scores as follows: radius, -1.75; spine, -1.45; femoral neck, -2.40; Ward's triangle, -2.41; and trochanter, -1.42. These values altered when calculated for the patient's age by the use of sex- and race-specific regressions against age in a healthy, non-fracture population. The age-corrected Z-scores were as follows: radius, -0.09; spine, -0.18; femoral neck, -0.79; Ward's triangle, -0.44; and trochanter, -0.80. Thus, although our patients had absolute osteopenia at all skeletal sites when compared with young normals, when compared with age-matched normals (relative osteopenia) the only site with a noticeable deficit was the femur. Interpretation of the extent of osteopenia by comparison with young normals may lead to different conclusions than when an age-matched population is used. Patients with hip fractures had a preferential deficit in density of the femur when compared with normal women of their age.

Seventy-one white women within 6 months to 6 years postmenopause were randomly assigned to three treatment groups: (a) placebo, (b) calcium, (c) cyclic estrogen-progestin plus calcium. Calcium was given as calcium carbonate with meals to attain an intake of 1,700 mg daily in the latter two groups. All women received 400 IU of vitamin D daily. Samples were obtained at baseline and after 2 months therapy. The hormonal treatment group had a decline in serum calcium, osteocalcin and urinary hydroxyproline and an increase in levels of calcitonin, parathyroid hormone and calcitriol. The increase in the latter two measurements could have resulted from the drop in serum calcium, it is also possible that the increase in calcitonin levels was a result of calcium supplementation. Although all these changes were statistically significant for the estrogen treatment group when considered alone, analysis of variance including the 3 groups demonstrated significance for the estrogen group for the parameters of skeletal metabolism but not for the changes in the calciotrophic hormones. There was an increase in serum calcium (p = 0.05) in the calcium augmentation group. It would be of interest to determine the effects of higher intakes of calcium in both the calcium and the estrogen treatment groups and to further explore differences in effects on bone remodeling between the two treatment approaches as well as the possibility of a additive effects. Early effects of estrogen replacement reduce bone remodeling whereas calcium supplementation to 1,700 mg per day of Ca CO3 did not appear to affect the parameters of bone remodeling.

The influence of exercise and immobilization on magnesium (Mg) balance, as influenced by vitamin D, was evaluated in female Sprague-Dawley rats that were divided into four groups: exercised fed ad libitum, pair-fed exercised, immobilized, and control. After 9 weeks, Mg absorption and retention were higher in the exercised groups than in the control group; however, immobilization resulted in an increase in the urinary excretion of Mg and a negative Mg balance. Serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] were higher in the exercised group than in the control group. The tibial content of Mg was higher in both exercise groups and lower in the immobilized than in the control group. In an additional experiment to evaluate the Mg balance during early adaptation to exercise training, no change was seen in Mg absorption and balance during the first 5 weeks of exercise, although serum levels of 1,25(OH)2D increased significantly. Immobilization resulted in a decrease in Mg retention without any effect on intestinal absorption. Urinary Mg was consistently higher in the exercised and immobilized groups than in the control group. Prolonged exercise training, after adaptation, increases and longer immobilization decreases intestinal absorption and retention of Mg. The influence of physical activity on Mg absorption is not necessarily mediated by vitamin D. Physical activity may influence mineral absorption by a mechanism associated with growth.

Cross-sectional and longitudinal changes in body composition with age were examined in white women to determine the relationship of body cell mass to menopause and of body fat to bone mass. There was statistical evidence for a curvilinear component to loss of total body potassium with negligible rates of loss before menopause. Longitudinal measurements also indicated a relationship between the proximity to menopause and the rate of loss of potassium. Total body potassium was significantly related to total body calcium and bone density of the spine, radius, and femoral neck. Total body fat was not related to any of these measurements. We found no evidence that adiposity plays a major role in protecting against bone loss.

The aim of this study was to examine the effect of exercise training on long bone and vertebra in young and adult ovariectomized rats. Female Sprague-Dawley rats, aged 6 weeks (young) and 10 months (adult) were divided into four groups: sham-operated control, ovariectomized, sham-operated exercised and ovariectomized exercised. The animals were pre-labeled with H-3-tetracycline for evaluation of bone resorption. Ovariectomy resulted in increased bone resorption in both the femur and fifth lumbar vertebra (L-5) of young and adult rats as determined by H-3-tetracycline retention in bone. The calcium content of L-5, but not of the femur, was also decreased by ovariectomy in these rats. Exercise increased the calcium content in both the femur and L-5 of the sham-operated and ovariectomized young rats. These results are consistent with increased bone retention of H-3-tetracycline by exercise, suggesting that exercise suppresses bone resorption. In adult rats, the effects of exercise on bone were not as consistent as those in young rats. In sham-operated animals, exercise significantly increased femoral calcium content. With ovariectomy, however, vertebral calcium content was significantly suppressed by exercise. In conclusion, exercise in young rats decreases both basal and ovariectomized-induced bone resorption and increases femoral and vertebral bone mass in ovariectomized animals. In adult rats, these effects were not apparent under the conditions of treadmill training used in this experiment.