Faculty Bibliography

Glucocorticoids enhance the movement of fluid and sodium in the duodenum, thereby resulting in an increase in the passive transport of calcium. Since passive transport of calcium predominates in the distal intestinal segments, the influence of glucocorticoids on calcium and fluid transport in the duodenum, mid-jejunum, ileum, and colon of the rat was studied. Calcium transport and fluid absorption was determined by the in vivo ligated loop technique. One segment was ligated in each animal. Under either normal osmolarity or hypertonic conditions, administration of cortisone stimulated intestinal fluid absorption in each segment of the small intestine, but not in the colon. Since the final fluid sodium concentration was not altered, cortisone enhanced net sodium absorption in proportion to the increase in fluid transport. Glucocorticoids inhibited the active transport of calcium in the proximal regions of the small intestine by bidirectional changes in calcium flux. However, the inhibitory effect was not apparent under the conditions where passive transport predominates. The stimulation of passive transport in the mid-jejunum overcomes the inhibition of active transport. In the ileal region, glucocorticoids increased active transport of calcium by 165%, whereas the enhancement of calcium transport under conditions where passive transport predominated reached 217%. This result indicates that both active and passive transport of calcium were enhanced by glucocorticoid treatment. In the colon, glucocorticoids increased active transport by 170%. However, the magnitude of the increase in calcium transport was less under conditions where passive transport predominates (129%), indicating that glucocorticoids stimulate the active transport of calcium in the colon with no appreciable stimulation of passive transport.

Mineral metabolism was studied by the metabolic balance technique in rats with and without administration of caffeine. Caffeine was injected subcutaneously each day at either 2.5 mg or 10 mg/100 g body weight for 2 wk before the balance studies. Urinary volume excretion was higher in the group given caffeine than in the control group, but the creatinine clearance was not different. Urinary excretion of potassium, sodium, inorganic phosphate, magnesium and calcium, but not of zinc and copper, was also higher in the rats given caffeine. The rank order of the difference was the same as the percent of ingested mineral excreted in urine in the absence of caffeine. Caffeine caused a negative balance of potassium, sodium and inorganic phosphate. There was no significant difference from the control levels and in the apparent metabolic balance of calcium and magnesium. The urinary and fecal excretion of zinc and copper were found to be unaffected by caffeine. It is suggested that chronic administration of caffeine may lead to a tendency toward deficiency of those minerals that are excreted primarily in urine.

With stepwise multiple logistic regression (MLR), probabilistic classification equations were developed to identify asymptomatic women who are at risk for development of fracture of the spine. Clinically normal women with low TBCa/square root H ratios can be classified as at risk for osteoporosis prior to their developing spinal compression fractures. With receiver operating characteristic (ROC) analysis, it was possible to verify the accuracy of the MLR model to discriminate "normal" women at risk, with high sensitivity and specificity. With the MLR model, discrimination of osteoporotic women (50-59 years) was made correctly for 86.2% of the total osteoporotic subjects with the TBCa data. Similar models were derived from the photon absorptiometry data. From the spinal density (BDs) data, correct classification in the 50-59 year group was 55.6% of the total osteoporosis subjects; from the radius density (BMCr) data, the corresponding value was 31%. The highest probability of identifying osteoporosis in all age categories was, therefore, on the basis of TBCa data. Similar, but less accurate discrimination was achieved with the BDs and BMCr data. These conclusions were confirmed by the application of receiver operating characteristic (ROC) analysis. Correct identification of the population at risk permits the timely and efficient application of therapeutic programs prior to onset of fracture. In a serial study of 104 peri-menopausal women, for example, it was possible to determine the P value for individuals measured annually over a 3-10 year period and thus to predict normal individuals at risk for developing osteoporosis each year.

It is not known why the intestinal active transport of calcium per unit of mucosal mass is not affected by hypophysectomy (HX) even though serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and intestinal calcium-binding protein are decreased. In order to study the effect of HX on the quantity of intestinal receptor of 1,25(OH)2D3 and its binding characteristics, the intestinal total occupied and unoccupied binding sites for 1,25(OH)2D3 were measured, by the use of the mercurial reagent mersalyl, in the intestine of HX and age-matched control rats. In addition, the effect of bovine growth hormone (bGH) replacement on the quantity of both binding states was examined in the HX rats. Results of Scatchard analysis and sucrose density gradients showed that the 3.5S receptor of the HX rat intestine was not distinguishable from that seen in the intact rat intestinal cytosol. Under vitamin D-supplemented conditions, HX was shown to reduce the levels of occupied receptors when the data were expressed on the basis of cytosolic protein. The reduced occupied sites could, in fact, have resulted from the reduction in plasma 1,25(OH)2D3 levels. No synthesis rates were determined. The unoccupied and total binding sites for 1,25(OH)2D3 per length of intestine were lower in the HX group than in the intact group. Administration of bGH resulted in an increase of endogenously occupied binding sites without affecting the total binding activity. Under vitamin D-depleted (-D) conditions, the total binding activity (intestinal) for 1,25(OH)2D3 was increased in the intact but not in the -DHX rats. Administration of bGH to the -DHX rat resulted in no effect on the binding levels of 1,25(OH)2D3 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone mass of the total skeleton and distal radius were measured by in vivo neutron activation analysis and single photon absorptiometry, respectively, in 403 healthy white women and 151 healthy white men. In addition, the density of L-2 to L-4 (bone mineral content of the spine [BMCs]) was measured by dual photon absorptiometry in 159 of these women and in 56 women with the vertebral crush fracture syndrome. The rate of loss of total body calcium (TBCa) and bone mineral content of the radius (BMCr) was linear in men and was slower than in women. The best fit for TBCa and the bone mineral content of the distal radius and spine as a function of age in women was with a two-phase regression. The TBCa and BMCr could be used as well as BMCs to identify women with crush fractures. The ratios of BMCs/TBCa, BMCs/BMCr, and TBCa/BMCr did not differ among women with crush fractures and age-matched normal individuals. Our data do not support the hypothesis that women with vertebral crush fractures have preferential loss of spinal bone.

Sixteen healthy male volunteers exercised on a bicycle ergometer starting at 40% Vo2max and progressing at 5-minute intervals up to 75% Vo2max over a 20-minute period. Blood was drawn from an indwelling venous catheter at baseline, at 5 minutes through 20 minutes, and at 10 and 20 minutes after the exercise was ended. Significant increases (which returned toward baseline in the rest period) were observed during the exercise period in total calcium and calcium ion activity, phosphate, potassium, magnesium, albumin, and lactic acid levels. Plasma volume (based on hematocrit value) decreased during the exercise period. Serum parathyroid hormone levels decreased and calcitonin levels increased at the early period of the short-term exercise. Although hemoconcentration was of sufficient magnitude to explain the change in calcium ion activity, the increase in potassium and phosphate were caused in part by additional factors.

A 24 month randomized parallel study of the treatment of postmenopausal osteoporosis with calcitonin alone v calcitonin alternating with growth hormone (combined treatment) was conducted. Each group received 1000 mg daily of oral calcium supplements. The rate of change in total body calcium for the combined and calcitonin groups was + 1.68%/yr and + 1.33/yr, respectively (P less than .05). However, the difference in the two groups was not statistically significant. Further, the total body calcium level did not increase after 12 to 18 months of treatment. There was significant difference in the rates of change of bone mineral content (BMC) of the radius for the two groups, with a loss of BMC in the combined treatment group (F = 4.80, P less than .05). Calcitonin treatment is effective in producing an increment in bone mass. The addition of growth hormone to this regimen appears to have a deleterious effect on cortical bone mass.