Stanton H. Cohn

Prevention of Involutional Bone Loss by Exercise

To ascertain whether exercise could prevent involutional bone loss, we studied 18 postmenopausal women, half of whom exercised for 1 h three times a week. Total and regional bone mass were measured before and after 1 year of exercise by the techniques of total-body neutron activation analysis (total body calcium) and photon absorptiometry (bone mineral content) of the distal radius. Total body potassium was measured by whole body counting. Bone mineral content and total body potassium did not change significantly in either group. Total body calcium increased in the exercise group from 781 +/- 95 g of 801 +/- 118 g (SD). In contrast, total body calcium decreased in each subject in the sedentary group. The daily calcium balance derived from the difference in total body calcium measurements was significantly different in the two groups of women (P less than 0.001). These data support the hypothesis that exercise can modify involutional bone loss.

Risk factors for postmenopausal osteoporosis.

Fifty-eight women with postmenopausal osteoporosis (crush fracture of the spine) were compared with 58 age-matched normal women. The osteoporotic women had lower total-body calcium levels and bone mineral content of the radius, had undergone an earlier menopause, smoked cigarettes more, and had breast-fed less often. They also had lower levels of estrone, estradiol, and testosterone and reduced levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. These findings suggest the presence of changeable risk factors for the development of osteoporosis. Smoking should be discouraged. An adequate intake of calcium and vitamin D should be ensured. It is the opinion of the authors that those women who have had an early menopause or who have a low bone mass at the time of menopause should be given the choice of medically supervised replacement therapy with estrogen and progesterone.

Comparative skeletal mass and radial bone mineral content in black and white women

The age-related changes in both skeletal mass and muscle mass were directly measured in normal black women ages 30-80 yr. The levels of total-body calcium (TBCa) were determined with the use of in vivo neutron activation. The muscle mass was measured by wholebody counting of 40K. In the same population, the bone mineral content of the radius was measured using a photon absorptiometric technique. Although there was no significant difference in stature, black women had a greater skeletal mass and bone mineral content of the radius than age-matched white female subjects. When the TBCa values were normalized for body size (i.e., corrected for height and lean body mass), the TBCa was still higher for the black women but not as high as the absolute TBCa values. Clearly, it is the larger muscle mass (as reflected by the 40K measure) in relation to weight and height that accounts for this difference. The lower prevalence of fracture and osteoporosis observed in black women relative to white women is due in part to this greater quantity of skeleton. American black women with a higher bone density (i.e., skeletal mass) maintain mechanical integrity of the skeleton longer than individuals with a lower bone density. It is suggested that the larger muscle mass in black women is, in part, a determinant of their increased skeletal mass and is partly responsible for their apparent resistance to osteoporosis and fracture of the skeleton.

Compartmental body composition of cancer patients by measurement of total body nitrogen, potassium, and water

Quantitative measurement was made of body composition in patients with several forms of neoplastic disease. Total body nitrogen was determined by means of the prompt gamma neutron activation technique; total body potassium was measured with the use of a whole body counter. The mass and protein content of the muscle compartment and nonmuscle lean tissue were estimated by application of the technique of compartmental analysis. Total body water, determined simultaneously with the use of tritium label, provided a measure of lean body mass. From these data, the body fat can be inferred. The prompt gamma neutron activation and whole body counting techniques represent a considerable advance over the balance and radioisotope techniques used in earlier studies. The new techniques make possible sequential studies over prolonged periods of time with a considerable degree of accuracy. The loss of body weight by patients with solid tumors consisted primarily of the loss of muscle mass and body fat. Even in severe wasting, the patients appear to retain significant amounts of body fat. It is the skeletal muscle which is predominantly lost; the visceral life-supporting system is, to a considerable extent, spared. The nonmuscle tissue including the visceral fraction did not change in this study, and actually appeared to increase in size when comparison was made with the normal contrast population. The loss of total body water was slight in the cancer patients studied.

Changes in body chemical composition with age measured by total-body neutron activation☆

Total-body levels of calcium and phosphorus (reflecting skeletal mass) and total-body levels of potassium (reflecting muscle mass) were measured by neutron activation analysis in 39 men and 40 women ages 30-90 yr. In order to intercompare the total body calcium (TBCa) values in a heterogeneous population, such as this, it was necessary to normalize the data for skeletal size. The normalization consisted of dividing the absolute calcium level by the predicted calcium level for each individual matched to a set of critical parameters. The parameter used in the computation of normal values were age, sex, muscle mass, i.e., total body potassium (TBK) and height. For the calcium data of the women, it was necessary to add an age correction factor after the age of 55 yr. The calcium ratio(mean ratio of the predicted to measured TBCa) in men was 1.000 +/- 7.8% and in women 0.996 +/- 7.1%. The TBCa of normal males and females can thus be predicted to +/- 13% (at the 90% confidence level). An exception to this was found in males (70-90 yr) who exhibited a mean calcium ratio greater than 1.13. The derivative of TBCa with time was determined for this population of men and women by taking into account the dependency of calcium on three time dependent variables, height, TBK, and an explicit age correction factor in the case of the women. The mean rate of loss of TBCa in women was 0.37% and 1.1% per year before and after menopause (50 yr). In the males, the average rate of loss of TBCa was 0.7% per year after 50 yr of age. The pattern of total body phosphorus (TBP) loss with age paralleled that of TBCa as the ratio of TBP/TBCa was rather constant with age. The constancy of the ratio suggests that the mineral composition of bone does not change significantly with age. The rate of loss of TBK with age was also related directly to that of TBCa. The mean ratio of TBK/TBCa was 9.9 in females and 8.0 in males and this ratio remained relatively constant from 30-70 yr. Thus, the mechanism responsible for the loss of bone with age, whether nutritional deficiency or decreased gonadal function and physical activity may also be responsible for the loss of muscle mass with age.

Skeletal mass and body composition in marathon runners

Skeletal and lean body mass was measured in 30 male marathon runners and in 16 subjects of comparable ages who were relatively sedentary. Skeletal mass was measured by total body neutron activation analysis (total body calcium—TBCa) and photon absorptiometry of the distal radius (bone mineral content—BMC). Lean body mass was estimated by the measurement of 40K in a whole body counter (total body K—TBK). The marathon runners were slightly taller and lighter than the contrast group; the bone width of the radius was essentially the same for both groups. When the values for TBK and TBCa were corrected for age and body size, the marathon runners were found to have values that were 7% (p < .002) and 11% (p < .001) higher, respectively. The values of BMC were somewhat elevated in the marathon runners but this increase in regional bone mass was not statistically significant. These data suggest that marathon running may be associated with prevention of the changes that occur in body composition with aging and raise the possibility that exercise may prevent the involutional loss of skeletal and lean body mass.

Critical concentrations of cadmium in human renal cortex: Dose‐effect studies in cadmium smelter workers

Cadmium was measured in vivo in the left kidney and liver of 82 industrially exposed workers and 10 control subjects. The range of Cd values for the industrial group was 0.9-57 mg for the whole kidney and 0.8-120 ppm for the liver, compared to 0.4-11.8 mg and 0.6-7.9 ppm for the control group. Below 40 ppm in the liver, the kidney Cd burden tended to increase with increasing liver concentration. Above 40 ppm, the kidney Cd content decreased as the liver concentration increased. This biphasic relation between Cd in the kidney and the liver for all subjects showed a critical level of approximately 31 mg Cd in the kidney. Estimates of the critical level by beta 2-microglobulin and urinary protein measurements yielded critical values of 31-42 mg Cd for the whole kidney (300-400 microgram/g for the renal cortex).

Coherence treatment of postmenopausal osteoporosis with growth hormone and calcitonin

SummaryFourteen women with postmenopausal osteoporosis, all having at least one vertebral crush fracture, were randomly assigned to two treatment arms, each lasting 24 months. The coherence treatment group (7 patients) was treated in the following sequence: human growth hormone (hGH) 7 IU subcutaneously daily for 2 months, followed by 3 months of salmon calcitonin (CT), 100 MRC units every other day. After a 3 month rest period, this sequence was repeated twice. The contrast group (7 patients) was treated intermittently with salmon CT given in the same time periods and at the same dose as in the coherence treatment group. Bone mass was measured every 4 months by neutron activation analysis for total body calcium (TBCa) and by single photon absorptiometry for bone mineral content (BMC) of the distal radius. Although there were no significant differences between the two groups (two-way ANOVA), the rate of change in TBCa in the coherence treatment group was significantly different from zero (F=3.8,P<.05) and was +2.3%/year. The increase in bone mass appeared to be sustained throughout the 2 year study, in contrast with previous studies where a plateau effect was observed with calcitonin given alone or continuously with growth hormone. No significant change was found in bone histomorphometric values measured before and after treatment in 4 patients from each group.

Body composition changes in children receiving human growth hormone

Abstract Skinfold thickness was found to decrease during the first 6–10 wk and then remain constant when human growth hormone therapy was begun in 34 growth hormone-deficient children. Linear growth increased at a constant rate during the first 6 mo. Two children, who routinely received their injection in the same arm at the same site, developed a localized area of markedly diminished subcutaneous fat at the injection site, Height, weight, total-body potassium, and triceps skinfold thickness were measured at 2-mo intervals in nine children receiving human growth hormone. Total-body potassium was measured with the 54-Nal detector whole-body counter of the Brookhaven National Laboratory. The study extended over a period of 20 consecutive mo. Triceps skinfold thickness rapidly decreased during the initiation of therapy with growth hormone, and returned to pretreatment values during a 5-mo control period when therapy was temporarily discontinued. Rate of weight gain was most rapid during this 5-mo control period and was reduced during two periods when growth hormone was being administered. Total body potassium and height increased very little during the control period when weight gain was greatest, and both increased rapidly during the two periods of growth hormone treatment. The data show clearly the initial changes in body fat and lean tissue that occur when human growth hormone is administered to children with growth deficiency.

Metallothionein excretion in urine upon cadmium exposure: Its relationship with liver and kidney cadmium

The relationships between quantities of accumulated cadmium in the liver and kidney and those of metallothionein in urine was studied in occupationally exposed workers and experimentally exposed rats. Cadmium-exposed workers who had been employed at a cadmium production plant for periods of 8-29 years had significantly higher levels of cadmium in both liver and kidney and excreted significantly larger amounts of metallothionein in urine when compared with workers who had been employed for less than 1 year, with office workers at the plant or with control subjects having no known occupational exposure to cadmium. The excretion of metallothionein in urine of the cadmium-exposed workers appeared to be related to the levels of cadmium in both liver and kidney. A similar dose-effect relationship was also observed among rats given repeated subcutaneous injections of 5 mumol CdCl2/kg. However, in the rats the metallothionein excretion increased markedly when the liver and renal cortex Cd levels exceeded approximately 300 microgram/g and 200 microgram/g, respectively. It appears tht urinary metallothionein may be a useful biological indicator of liver and kidney cadmium levels.