Faculty Bibliography

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.

Intestinal active and passive transport of phosphate (Pi) was studied in hypophysectomized (HX) and intact rats using the in situ intestinal loop technique. Hypophysectomy resulted in a significant reduction of total Pi absorption under active transport conditions. However, when transport data were expressed on the basis of mucosal mass, the reduction was not apparent. Under passive transport conditions, net Pi absorption was lower in the HX rats even after correction for the decrease of mucosal mass. Administration of bovine growth hormone (bGH) did not change the intestinal Pi absorption in the HX rats. These results indicate that a decrease in mucosal mass following hypophysectomy is one of the factors that causes a decrease of intestinal Pi absorption.

The interrelation of glucocorticoids and 1,25 dihydroxycholecalciferol (1,25(OH)2D3) on intestinal calcium and phosphate absorption was investigated. The active and passive transport of calcium and phosphate was evaluated by the in situ intestinal loop technique. Administration of cortisone resulted in a decrease of the luminal fluid and an increase of the luminal calcium and phosphate concentration. Under active transport conditions, administration of cortisone resulted in a decrease of net calcium absorption through two mechanisms: (1) depressed vitamin D-dependent calcium absorption, (2) increased vitamin D-independent calcium backflux. The enhancement of bidirectional phosphate flux by cortisone was independent of 1,25(OH)2D3. An enhancement of water movement by cortisone resulted in an increase of luminal calcium and phosphate concentration which favors the passive diffusion of these ions. Enhanced calcium diffusion by cortisone compensates for the inhibitory effect of cortisone on vitamin D-dependent calcium transport. However, enhanced phosphate diffusion by cortisone is additive to the effect of 1,25(OH)2D3.

The effect of glucocorticoids on duodenal active and passive calcium transport was studied by the in situ intestinal loop technique, using 2.0 mM and 50 mM concentrations of calcium. The administration of prednisolone resulted in a significant increase of fluid and sodium absorption. The final luminal calcium concentration was increased in the prednisolone-treated group. Under conditions where active transport predominates (2 mM), glucocorticoids decreased lumen-to-plasma and increased plasma-to-lumen calcium flux, resulting in a decrease of net calcium absorption. Under conditions where passive transport predominates (50 mM), glucocorticoids did not decrease calcium absorption in the duodenum. These data suggest that under conditions where passive transport predominates, glucocorticoids indirectly enhance calcium absorption by an effect on water movement. Water movement enhances calcium absorption by concentrating unabsorbed calcium within the intestinal lumen. The increase in passive diffusion of calcium in the duodenum compensates for the inhibition of the active transport of calcium by glucocorticoids.

Intestinal active and passive transport of calcium were studied in hypophysectomized (HX) and intact rats using the in vivo duodenal loop technique. In the vitamin D-supplemented condition, hypophysectomy resulted in a decrease in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D]. Hypophysectomy prevented a gain in body weight and decreased intestinal mucosal weight and total calcium absorption. When the data were expressed per unit mucosal wet weight, duodenal active calcium transport was not different in the HX and intact groups, but passive transport was persistently decreased by hypophysectomy. Administration of bovine GH to the HX rats did not change the mucosal mass, but enhanced both active and passive duodenal transport to calcium. Vitamin D depletion for 6 weeks decreased serum 25-hydroxy-vitamin D and 1,25-(OH)2D levels in both intact and HX rats to about the same level. After bovine GH and 1,25-(OH)2D3 replacement, the calcium absorption studies suggest that 1) 1,25-(OH)2D3 enhances intestinal calcium passive transport as well as active transport in intact and HX rats; 2) GH enhances both active and passive transport of calcium in the presence of sufficient quantities of 1,25-(OH)2D; 3) this latter effect is independent of the metabolism of vitamin D; and 4) a decrease in mucosal mass is one of the factors that results in decreased calcium absorption after hypophysectomy.

To examine the effect of hypophysectomy on tissue alkaline phosphatase (EC 3.1.3.1) activity, studies were performed on mature rats. Hypophysectomy reduced the alkaline phosphatase activity in duodenum, kidney, and femoral bone. The decrease of alkaline phosphatase was greater in the intestine than in other organs studied. Intestinal alkaline phosphatase fell rapidly within 4 days post-hypophysectomy. In contrast, bone and kidney alkaline phosphatase activity had an initial lag period for 4 days after the hypophysectomy. Serum alkaline phosphatase also declined after hypophysectomy. The bone isoenzyme of serum alkaline phosphatase was reduced to a greater extent than the intestinal isoenzyme.

The effect of cortisone on jejunal active and passive phosphate transport was evaluated by the in situ intestinal loop technique using 1.2 and 50 mM concentrations of phosphate. Animals were divided into four groups: (1) intact, (2) hypophysectomized (HX), (3) HX plus cortisone, (4) HX plus 1,25-dihydroxyvitamin D3[1,25(OH)2D3]. The results of the experiment suggest that cortisone enhances jejunal phosphate absorption in HX rats through two mechanisms: (1) increased mucosal cell membrane permeability, (2) enhanced water movement, resulting in a rise of luminal phosphate concentration which favors the active and passive transport of phosphate. Stimulation of phosphate transport by cortisone is different from the unidirectional specific phosphate transport caused by 1,25(OH)2D3.

Total body phosphorus (TBP) and total body calcium (TBCa) were measured by neutron activation analysis and whole body counting in 82 white women who were 1-6 years postmenopausal. Mean TBP was 395 g +/- 6.3 (SE). There was no evidence for subgroups of patients with either higher or lower TBP. The TBP was significantly related to TBCa, as well as to the bone mineral content of the distal radius. Positive associations were found between TBP and urinary phosphate excretion as well as serum 1,25(OH)2D levels (r = 0.30; p = 0.017; n = 48). Serum phosphate was related to 1,25(OH)2D levels and the number of years since menopause.