Vitamin D3 and calcium to prevent hip fractures in elderly women.

BACKGROUND: Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. METHODS: We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. RESULTS: Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). CONCLUSIONS: Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

[Establishment of a transformed line of arterial smooth muscle cells]. / Etablissement d'une lignée transformée de cellules musculaires lisses artérielles.

Biology of the vascular cells is widely studied by means of cell culture techniques. In the present work the description of a transformed cell line of arterial smooth muscle cells is presented. The cell line, named V8, has been established from cells of adult rat aortic media. The cells presented proliferation characteristics in vitro, in soft agar, and in vivo in nude mice demonstrating a tumorigenic ability. This cell line provides an interesting model for the study of growth regulation of arterial smooth muscle cells specially in the areas of hypertension and atherosclerosis.

Selection of a strain of rats with spontaneous high cholesterolemia.

By means of an inbred selection procedure utilizing positive assortative mating, high (SHC: spontaneous high cholesterolemic) and low (SLC: spontaneous low cholesterolemic) blood cholesterol strains of rats were developed. This procedure was shown to be much more efficient in increasing than in lowering the blood cholesterol level. The diet used throughout selection was normal laboratory chow; therefore the high and low blood cholesterol levels occurred spontaneously. Since the 6th generation there has been no overlap between the blood cholesterol values of the animals of the two strains. The cholesterol increase with ageing was found to be strongly related to sex, but weakly to the genes governing the differences between SHC and SLC rats. Cholesterol enhancement following a hyperlipidic diet did not differ between strains or sexes. It appears that the SHC rat strain could be an interesting model, particularly in pharmacological research.

Variations in growth and cell cycle time of arterial smooth muscle cells cultured at low density.

The population kinetics of cultured rat arterial smooth muscle cells replated at various low densities were studied by direct counting and observation of the cells. Population doubling time decreases with increasing initial density of the culture. These variations in population doubling times depend on both the variation in the percentage of quiescent cells and on the variation of the mean cell cycle time of non-quiescent cells.

[Effect of adrenaline on the proliferation of the tunica media smooth muscle cells of rat aorta in culture]. / Action de l'adrénaline sur la prolifération de cellules musculaires lisses de média aortique de rat en culture.

The proliferation of Rat medial aortic smooth muscle cells in secondary cultures is increased with adrenalin. The maximal effect is obtained after 3 days and the increase is dose-dependent. Thus adrenalin might be one of the factors responsible for the proliferation of smooth muscle cells that could play a key role in the formation of the atherosclerotic plaque in vivo.

[Morphological and histochemical behavior of arterial tissue in normal and spontaneously hypo- or hypercholesterolemic rats on a normal or hyperlipidic diet]. / Comportement morphologique et histochimique du tissu artériel de rats génétiquement normo, hypo et hypercholestérolémiques à l'état normal et après régime hyperlipémiant.

Hypo and hypercholesterolemic rats strains were selected (Lyon) and compared to a normocholesterolemic one issued from the same race (Sprague-Dawley). The arterial tissue of these three strains at three ages (10-19-25 months) and their reactivity to an hyperlipidic diet (2 and 6 month duration) were studied using histological and histochemical technics. There were neither histological nor histochemical differences between the three strains whatever the ages. Therefore, at the present stage of selection, the genetic differences have not changed the arterial metabolism or its evolution during ageing. However the arterial reactivity of hypo and hypercholesterolemic strains towards an hyperlipidic diet was different: indeed both strains developed hypercholesterolemia, liver steatosis and diffuse intimal lipoidosis, but on the other hand the hypercholesterolemic rat alone demonstrated arterial cell proliferation. These data suggest that a same genetic trait can give rise to both a spontaneous hypercholesterolemia and an arterial hyperactivity against a superimposed hyperlipemia.

Proliferation of primary cultures from rat aortic media. Effects of hyperlipemic serum.

Tissue cultures have been made from explants of thoracic aortas to study the growth pattern of rat aortic mediacytes. Three parameters were measured weekly: the surface of the culture, the relative increase of this surface and the number of 3H-thymidine labelled cells per unit surface. The primary cultures showed two distinctive phases: a first phase with continuous growth followed by a plateau phase. We studied the growth effect of homologous hypercholesterolemic serum added to the cultures. The cell proliferation was affected by the cholesterol level in the medium and the stage of the culture at which serum incubation was initiated. An enhancing effect occurred in the rat resistant to such treatment in vivo.

Histological arguments for collagen and elastin synthesis by primary cultures of rat aortic media cells.

Using the histological staining methods of Weigert and of Masson on primary cultures of rat aortic media cells, we obtained additional proofs of the smooth muscle cell's ability to secrete collagen and elastin in vitro: the percentage of positive flasks with aorta rings was the same throughout the follow-up, but increased gradually for the new tissue growing around the rings.

[Formation of xanthomatous cells in vitro from the aortic media of the rat]. / Formation de cellules xanthomateuses in vitro à partir de media aortique de rat

The foam cell is viewed as a specific component of the atherosclerotic plaque found in human or experimentally induced in the animal. A study using light microscopy (staining with Sudan III) and electron microscopy was performed on cell cultures derived from rat aortic media. Sudanophilic and electron transparent vacuoles were observed in vitro in 11 week cultures. The sudanophilic cells were either scattered or crowded in clusters; some of them were found in a mitotic phase. Different serums were applied to the cultures starting from the 6th week: either calf serum (continuing the previous treatment), or normocholesterolemic rat serum (NCRS) or hypercholesterolemic rat serum (HCRS). Sudanophilic cells were observed more frequently in the cultures on exposure to HCRS than to NCRS (p less than 0.05). Thus it was possible to induce the formation of foam cells in vitro in cultures of arterial tissue derived from the rat, which is known to be resistant to atherosclerosis.

Primary cultures of rat aortic media: a growth stop phenomenon different from contact inhibition.

Cultures have been made from explants of thoracic aortas to study the growth pattern of aortic mediacytes. Explants from aortas of eight rats, aged between seven to eight weeks, were seeded. Three parameters were measured weekly from the second to the nineth week: the surface of the culture (S); the relative increment of this surface (delta S/S) and the number of 3H-thymidine labelled cells by the unit surface (n chi S-1) after autoradiography. The surface of primary culture, in relation to time, has roughly the shape of a sigmoidal curve. Growth is continuous until the fifth week and reaches a plateau beyond that time. The two other parameters decreased regularly during the first phase to attain a minimum at the beginning of the plateau-period; however new cells in the S-phase are still found in this second period.