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Biomedical subjects

R Rizzoli

Publications and source records attributed to R Rizzoli.

At least 91 records · Page 5Linked to original sources
PubMed1999

Vitamin D supplementation during infancy is associated with higher bone mineral mass in prepubertal girls.

The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and/or areal bone mineral density (aBMD) in later childhood. The design was a retrospective cohort study. One hundred and six healthy prepubertal Caucasian girls (median age, 8 yr; range, 7-9 yr) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a questionnaire sent to participating families and their pediatricians. Bone area (square centimeters) and bone mineral content (grams) were determined by dual energy x-ray absorptiometry at six skeletal sites. Vitamin D receptor (VDR) 3'-gene polymorphisms (BsmI) were also determined. The supplemented (n = 91) and unsupplemented (n = 15) groups were similar in terms of season of birth, growth in the first year of life, age, anthropometric parameters, and calcium intake at time of dual energy x-ray absorptiometry. The supplemented group had higher aBMD at the level of radial metaphysis (mean +/- SEM, 0.301+/-0.003 vs. 0.283+/-0.008; P = 0.03), femoral neck (0.638+/-0.007 vs. 0.584+/-0.021; P = 0.01), and femoral trochanter (0.508+/-0.006 vs. 0.474+/-0.016; P = 0.04). At the lumbar spine level aBMD values were similar (0.626+/-0.006 vs. 0.598+/-0.019; P = 0.1). In a multiple regression model taking into account the effects of vitamin D supplementation, height, and VDR genotype on aBMD (dependent variable), femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group (P = 0.02). Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls.

Absorptiometry, Photon↗
PubMed1999

Bone mineral mass and calcium and phosphate metabolism in young men: relationships with vitamin D receptor allelic polymorphisms.

The genetic bases of peak bone mass determinants are still poorly understood, particularly in males. We investigated the relationship between vitamin D receptor (VDR) 3'- and 5'-gene polymorphisms (as determined by the restriction enzymes BsmI and FokI) and bone mineral mass, and calcium and inorganic phosphate (Pi) metabolism in an homogeneous cohort of young healthy men. In 104 healthy subjects, aged 24.3 +/- 3.1 yr (mean +/- SD; range, 20.7-38.7), standardized bone mineral density (BMD; z-scores) at the levels of lumbar spine and femoral trochanter, i.e. bone mineral content adjusted for age, body size, and bone area, significantly differed between VDR 3'-end alleles (BsmI), whereas crude areal BMD or bone mineral content did not. Among BsmI homozygotes BB, BMD (z-scores) were significantly lower only in subjects also carrying the f allele at the VDR-5' polymorphic site (FokI). Serum PTH levels were significantly higher in the BB genotype at baseline and remained so under either a low or a high calcium-phosphorus diet. Moreover, on the low calcium-phosphorus diet, BB subjects had significantly decreased tubular Pi reabsorptive capacity and plasma Pi levels. Our results underline the importance of identifying multiple single base mutation polymorphisms within candidate genes of bone mineral mass and suggest a role for environmental/dietary factor interactions with VDR gene polymorphisms in peak bone mineral mass in men.

Adult↗
PubMed1998

Sequence and activity of parathyroid hormone/parathyroid hormone-related protein receptor promoter region in human osteoblast-like cells.

The parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor gene has been characterized in various species. The structure of its promoter and the regulation of its expression in human tissues have, however, not been clearly established yet. We characterized the region upstream of the PTH/PTHrP receptor gene and investigated its promoter activity in the human osteoblast-like SaOS-2 cells. In this region, three untranslated exons were localized, U1 and U2 by using a kidney cDNA, and U3 by homology with the mouse gene. In human osteoblast-like cells, a distal promoter (P1) was found to be inactive, as evaluated by luciferase reporter gene assays, in contrast to the situation found in human and mouse kidney tissue. A second promoter (P2), previously described in mouse and human kidney, was shown to be active in human osteoblast-like SaOS-2 cells. We found a hitherto uncharacterized promoter (P3), closely upstream of the ATG start codon. The activities of P2 and P3 were not additive. These results provide important information on the structure of the 5' flanking region of the human PTH/PTHrP gene receptor.

Animals↗
PubMed1998

[Calciotropic hormones and integrated regulation of calcemia and calcium balance].

Calcium homeostasis is regulated by fluxes occurring at the levels of bone, kidney and intestine, fluxes which are controlled by calciotropic hormones. Bone resorption is stimulated by parathyroid hormone and by the bioactive metabolite of vitamin D, 1,25-dihydroxyvitamin D, or calcitriol. The renal tubular capacity to reabsorb calcium is regulated by parathyroid hormone, and calcium intestinal absorption is increased by calcitriol. Any modification of extracellular calcium concentration triggers a series of hormonal homeostatic reactions, aimed at changing these fluxes and correcting thereby calcium homeostasis perturbations. The evaluation of these fluxes provides information on the pathophysiological mechanism(s) implicated. Then the determination of calciotropic hormones circulating levels allows one the confirmation of the diagnosis evoked.

Bone and Bones↗
PubMed1998

[Extraparathyroid hypercalcemia].

Hypercalcemia is the consequence of increased calcium fluxes into extracellular fluid. The origin of calcium is bone resorption, renal tubular reabsorption, rarely intestinal absorption. Among inpatients, the most frequent cause of hypercalcemia is tumor, with pathophysiological mechanisms implicating both enhanced bone resorption and increased renal tubular reabsorption of calcium. The presence of hyperosteolysis in most patients with hypercalcemia of non parathyroid origin, constitutes the rationale for the use of potent bone resorption inhibitors, such as bisphosphonates, in the acute treatment of hypercalcemia.

Absorption↗
PubMed1998

Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Elderly persons who have osteoporotic hip fracture are often undernourished, particularly with respect to protein. Protein malnutrition may contribute to the occurrence and outcome of hip fracture. OBJECTIVE: To investigate whether oral protein supplements benefit bone metabolism in patients with recent hip fracture. DESIGN: 6-month, randomized, double-blind, placebo-controlled trial with a 6-month post-treatment follow-up. SETTING: University orthopedic ward. PATIENTS: 82 patients (mean age, 80.7 +/- 7.4 years) with recent osteoporotic hip fracture. Patients received calcium supplementation, 550 mg/d, and one dose of vitamin D, 200,000 IU (at baseline). INTERVENTION: Protein supplementation, 20 g/d, or isocaloric placebo (among controls). MEASUREMENTS: Bone mineral density, biochemical markers of bone remodeling, calciotropic hormone levels, biochemically evaluated nutritional and immunologic status, and muscle strength were measured every 6 months. RESULTS: Compared with controls, patients who received protein supplements had significantly greater increases in serum levels of insulin-like growth factor-I (85.6% +/- 14.8% and 34.1% +/- 7.2% at 6 months; difference, 51.5 percentage points [95% CI, 18.6 to 84.4 percentage points]; P = 0.003) and an attenuation of the decrease in proximal femur bone mineral density (-2.29% +/- 0.75% and -4.71% +/- 0.77% at 12 months; difference, 2.42 percentage points [CI, 0.26 to 4.59 percentage points]; P = 0.029). Seven and 13 new vertebral deformities were found among patients who received protein supplements and controls, respectively (P > 0.2). Median stay in rehabilitation wards was shorter for patients who received protein supplements than for controls (33 days [CI, 29 to 56 days] and 54 days [CI, 44 to 62 days]; difference, 21 days [CI, 4 to 25 days]; P = 0.018). CONCLUSION: Protein repletion after hip fracture was associated with increased serum levels of insulin-like growth factor-I, attenuation of proximal femur bone loss, and shorter stay in rehabilitation hospitals.

Activities of Daily Living↗
PubMed1998

Heritable and nutritional influences on bone mineral mass.

Osteoporosis is the net result of the maximal amount of bone mineral mass achieved by the end of pubertal growth (peak bone mass) minus post-menopausal and elderly bone losses. Peak bone mineral mass is determined from early childhood by both heritable and environmental factors. Recent developments in the molecular epidemiology of osteoporosis have shown the interest, but also the limitations, of specific molecular markers, such as the vitamin D receptor gene polymorphisms Bsm 1 and Fok 1, to explain bone mineral density differences across the population. Importantly, however, interactions between VDR gene polymorphisms and environmental factors, particularly dietary calcium, have provided new insights into the complex determination of bone mineral mass.

Aged↗
PubMed1998

Inositides in the nucleus: taking stock of PLC beta 1.

The nucleus was shown to be a site for inositol lipid cycle which can be affected by treatment of quiescent cells with growth factors such as IGF-I. In fact, the exposure of Swiss 3T3 cells to IGF-I results in a rapid and transient increase in nuclear PLC beta 1 activity. In addition, several other reports have shown the involvement of PLC beta 1 in nuclear signalling in different cell types. Indeed, PLC beta 1 differs from the PLC gamma and della isozymes in that it has a long COOH-terminal sequence which contains a cluster of lysine residues that are critical for association with the nucleus. Although the demonstration of PtInsP and PtdInsP2 hydrolysis by nuclear PLC beta 1 established the existence of nuclear PLC signalling, the significance of this autonomous pathway in the nucleus has yet to be thoroughly clarified. By inducing both the inhibition of PLC beta 1 expression by antisense RNA and its overexpression we show that this nuclear PLC is essential for the onset of DNA synthesis following IGF-I stimulation of quiescent Swiss 3T3 cells. Moreover, using a different cell system, i.e. Friend erythroleukemia cells induced to differentiate towards erythrocytes, it has been evidenced that there is a relationship between the expression and activity of nuclear PLC beta 1 and the association of PI-PT alpha with the nucleus in that, when PLC activity ceases, in differentiated and resting cells at the same time there is a dramatic decrease of the association of PI-PT alpha with the nucleus.

3T3 Cells↗
PubMed1998

Fluoride potentiates the osteogenic effects of IGF-I in aged ovariectomized rats.

The molecular mechanisms whereby fluoride stimulates osteogenic cell proliferation are not clearly established. However, fluoride has been shown to enhance the protein tyrosine phosphorylation of various constituents of intracellular signaling cascades in osteoblastic cells following stimulation of growth factor receptors such as the insulin-like growth factor-I (IGF-I) receptor. Such in vitro findings provided the rationale for testing whether the administration of fluoride could enhance IGF-I effects on bone mass in vivo. Adult ovariectomized osteopenic rats were treated with sodium fluoride at a dose of 6 mg/kg per day in drinking water for 8 weeks in association with IGF-I either at a dose of 2 mg/kg per day, which is capable of increasing bone mass, or at a lower dose without detectable skeletal effects. Bone mineral density (BMD) and content (BMC) were evaluated by dual-energy X-ray absorptiometry at the levels of the lumbar spine and proximal, midshaft, and total tibia before and after 8 weeks of treatment. During this period, fluoride alone did not significantly influence BMD/BMC at any skeletal site. However, it potentiated the effect of the higher dose of IGF-I on bone mass at the level of the proximal tibia. When administered in combination with the lower dose of IGF-I, which per se did not modify bone mass, it appeared to sensitize tibial bone to the effects of IGF-I. These changes were associated with a concomitant increase in osteocalcin, taken as a reflection of bone formation. These results indicate that fluoride could potentiate the osteogenic effects of IGF-I on bone in adult ovariectomized rats.

Absorptiometry, Photon↗
PubMed1998

Arginine increases insulin-like growth factor-I production and collagen synthesis in osteoblast-like cells.

Protein-energy malnutrition, which is common in elderly patients with osteoporotic hip fractures, is associated with reduced plasma levels of insulin-like growth factor-I (IGF-I). IGF-I is an important regulator of bone metabolism, particularly of osteoblastic bone formation both in vivo and in vitro. Pharmacological doses of arginine (Arg) increase growth hormone (GH) and IGF-I serum levels. Whether amino acids, particularly Arg, can directly modulate the production of IGF-I by osteoblasts is not known. We investigated the effects of increasing concentrations of Arg on IGF-I expression and production, alpha1(I) collagen expression and collagen synthesis, and cell proliferation and cell differentiation, as assessed by alkaline phosphatase (ALP) activity and osteocalcin (OC) release, in confluent mouse osteoblast-like MC3T3-E1 cells. The addition of Arg (7.5-7500 micromol/L, equivalent to 0.1- to 100-fold human plasma concentration) for 48 h increased IGF-I production (adjusted for cell number) in a concentration-dependent manner with a maximum of 2.3 +/- 0.3-fold at 7500 micromol/L Arg [x +/- standard error of the mean (SEM), n = 3 experiments, p < 0.01]. Arg (7.5-7500 micromol/L) increased the percentage of de novo collagen synthesis in a concentration-dependent manner (2.1 +/- 0.4-fold with 7500 micromol/L Arg, p < 0.001) and ALP activity with a maximal stimulation of 144% +/- 13% plateauing at 750 micromol/l Arg (p = 0.002). The steady state level of IGF-I messenger ribonucleic acid (mRNA) and alpha1(I) collagen mRNA (both normalized to cyclophilin mRNA) of cells incubated with Arg at high (100-fold) or low (0.1-fold) human plasma concentrations, was 1.4 +/- 0.2, 1.2 +/- 0.2, and 1.1 +/- 0.2 after 24 h for the 7.5, 1.8, and 0.9 kb IGF-I mRNA transcripts, respectively (n = 3 experiments) and 1.5 +/- 0.2 and 3.1 +/- 0.7 after 24 and 48 h, respectively, for the combined analysis of the 5.6 and 4.7 kb alpha1(I) collagen mRNA transcripts (n = 3 experiments). A maximal mitogenic effect (cell number) of +21% +/- 3% (p < 0.01) was obtained with 1000 micromol/L Arg. In contrast, Arg (7.5-7500 micromol/L) induced a reduction of OC production, which reached 30% +/- 3% with 7500 micromol/L Arg (p = 0.02). In conclusion, Arg stimulated IGF-I production and collagen synthesis in osteoblast-like cells. Thus, Arg may influence bone formation by enhancing local IGF-I production.

3T3 Cells↗
PubMed1998

Accumulation of catalytically active PKC-zeta into the nucleus of HL-60 cell line plays a key role in the induction of granulocytic differentiation mediated by all-trans retinoic acid.

The effect of differentiating doses of all-trans retinoic acid (ATRA, 10(-6) M) and vitamin D3 (10(-7) M) was investigated on the nuclear levels of endogenous ceramide and protein kinase C-zeta (PKC-zeta) catalytic activity in HL-60 myeloid cells. ATRA induced a parallel increase of ceramide and catalytically active PKC-zeta into the nuclear compartment of HL-60 cells (peak at 72 h). On the other hand, vitamin D3 increased the levels of nuclear ceramide and PKC-zeta activity to a lesser extent and with a delayed kinetics compared to ATRA (peak at 96 h). Pretreatment of HL-60 cells with high pharmacological concentrations of exogenously-added C2-ceramide (10(-6) M) completely blocked the ATRA-mediated activation of nuclear PKC-zeta. Exogenous C2-ceramide (10(-6) M) also inhibited the granulocytic differentiation induced by ATRA, whereas it did not affect monocytic differentiation mediated by vitamin D3. Transient transfection experiments performed with a plasmid construct containing a constitutively active mutated form of the PKC-zeta cDNA fused in 3' to a fluorescent tag protein (pEGFP-PKC-zeta) demonstrated that the overexpression of catalytically active PKC-zeta was not accompanied by the appearance of a differentiated morphology. These findings suggest that nuclear PKC-zeta is necessary but not sufficient to induce granulocytic differentiation of HL-60 myeloid malignant cells.

Blotting, Western↗
PubMed1998

Apoptosis induced by NK cells is modulated by the NK-active cytokines IL-2 and IL-12.

NK cells kill sensitive targets via exocytosis of cytoplasmic granules containing membrane damaging perforins and DNA damaging granzymes. Therefore, the target cell can either die by necrosis or by apoptosis. A third, non-secretory, mechanism of killing mediated by Fas-FasL interaction can be used by activated NK cells to kill Fas+ targets. Here, we have studied the modulation exerted by two NK active cytokines, IL-2 and IL-12, on the apoptosis-inducing activity of NK cells in NK-sensitive Fas- K562 and NK-insensitive Fas+ Raji cells. Our results show that apoptosis is preferentially induced at low target:effector ratios. Resting NK cells virtually do not induce apoptosis in target cells while IL-2 stimulation endows NK cells with the capacity of inducing apoptosis and IL-12 further enhances this effect against both targets. Finally, we demonstrate that cytokine-stimulated NK cells use both granzyme and Fas-FasL pathways of apoptosis induction.

Apoptosis↗
PubMed1998

Familial resemblance for bone mineral mass is expressed before puberty.

Genetic factors are known to explain a major proportion of peak bone mineral mass variance. Whether the influence of these genetic factors is expressed before the pubertal bone mineral mass accrual and whether there is tracking of bone mineral mass during pubertal growth, however, are not clearly established. We prospectively investigated correlations for bone mineral content (BMC), density, and bone size between prepubertal daughters and their premenopausal mothers. Height, weight, lumbar spine (LS), femoral neck (FN) and mid-femoral diaphysis BMC, bone area (BA), areal bone mineral density (aBMD), and volumetric bone mineral apparent density (BMAD) were evaluated in 138 mothers (mean age +/- SD, 40.0 +/- 4.0 yr) and their daughters (8.1 +/- 0.7 yr), who were then remeasured at yearly intervals for 2 yr. Eight-year-old prepubertal daughters had reached 78% and 44% of their mothers' height and weight, respectively. At the various skeletal sites, they had reached 33-43% of their mothers' BMC, 47-69% of their BA, 59-78% of their aBMD, and 75-105% of their BMAD. All body size and bone traits (age-adjusted Z-scores) were significantly correlated between prepubertal daughters and their mothers (r: 0.22-0.36, P < 0.01), except midfemoral diaphysis BMAD. Heritability estimates (1/2 h2), after adjustment for body size and dietary calcium intake, showed that 18-37% of bone traits were directly determined by maternal descent. During the next 2 yr, growth was accompanied by a marked increase of BMC, aBMD, and BA, whereas BMAD changed very little. In contrast, during this period, there were only minor changes in body size or bone trait Z-scores (i.e. < 0.5 Z-scores), which were thus highly correlated between consecutive measurements (r: 0.75-0.92, P < 0.0001). Accordingly, mother-daughter correlations remained unchanged over that period. Although more than 60% of peak bone mineral mass is gained during puberty (mostly at the expense of an increase in bone size while volumetric bone density slightly changes), familial resemblance for most bone traits is already present between daughters and their mothers before puberty. In the girls, moreover, yearly measurements were highly correlated, suggesting tracking of bone traits during pubertal growth. These results indicate that genetic susceptibility to osteoporosis may already be detectable in early childhood.

Adult↗
PubMed1998

Renal tubular reabsorption of phosphate is positively related to the extent of bone metastatic load in patients with prostate cancer.

Osteolytic metastases are often associated with decreased renal tubular reabsorption of phosphate. There is, however, no specific data on phosphate metabolism in metastases from prostatic cancer, which are generally osteoblastic. The aim of the present study was to investigate renal handling of inorganic phosphate (Pi) in prostatic cancer, in patients without or with skeletal metastases of various extents. Forty-eight patients were the subjects of this study. There were 39 with malignant disease, of whom 27 had bony metastases. Nine other patients had benign prostate hyperplasia. Biochemical indexes of prostatic tumor, renal tubular reabsorption of calcium and Pi, biochemical markers of bone remodeling, and relevant calciotropic hormones were measured and analyzed in relation to the extent of skeletal metastases, as assessed by bone scintigraphy. A higher bone metastatic load was associated with significantly greater prostate-specific antigen and prostatic acid phosphatase levels (P < 0.05), increased levels of biochemical markers of bone formation (P < 0.05) and resorption (P < 0.001), higher maximal renal tubular reabsorption of Pi (TmPi/GFR; P < 0.05), and higher urinary cAMP excretion (P < 0.05). Nine patients among those with bone metastases (n = 27) had higher TmPi/GFR than metastasis-free patients. These had a greater value of osteocalcin (P < 0.001). Also, 8 of these had relatively more extensive skeletal metastatic load. In patients with prostatic cancer, high skeletal metastatic load was accompanied by increased TmPi/GFR despite higher urinary cAMP excretion, which is supposed to reduce the TmPi/GFR. These results support the hypothesis that renal tubular reabsorption of Pi is capable of adaptation to meet demands for minerals in the face of enhanced bone formation.

Absorption↗
PubMed1998

Do dietary calcium and age explain the controversy surrounding the relationship between bone mineral density and vitamin D receptor gene polymorphisms?

Whether vitamin D receptor (VDR) gene polymorphisms are associated with osteoporosis is highly controversial. The relationship between VDR gene polymorphisms and bone mineral density (BMD) might, however, be modified by age-related and/or environmental factors. We studied the potential association between BMD and VDR genotypes in females from prepuberty to premenopause and prospectively investigated the interaction of VDR genotypes with dietary calcium and BMD changes during childhood. Bsm I VDR gene polymorphisms and BMD at the lumbar spine (LS) and femur (neck [FN] and midshaft [FS]) were assessed in 369 healthy Caucasian females, aged 7-56 years (143 prepubertal girls, 54 peri- and postpubertal adolescents, and 172 premenopausal adults). Femoral trochanter (FT) and distal radius BMD (metaphysis and diaphysis) were also measured in 101 of the prepubertal girls who participated in a 1-year, double-blind, randomized study of calcium supplementation (850 mg/day) versus placebo on bone mineral mass accrual. Among all females, 150 (40.7%) had bb, 167 (45.3%) Bb, and 52 (14%) BB VDR genotypes. In prepubertal and adolescent girls altogether, LS BMD (Z scores) was associated with VDR genotypes and was significantly lower in BB than in Bb or bb subjects. Trends for a similar difference were also detected at the FN level as well as on the mean BMD (Z scores) of the three sites measured (LS, FN, and FS). By contrast, no BMD differences were detectable among VDR genotypes in the adults. In 101 prospectively studied prepubertal girls, calcium supplementation significantly increased BMD at most skeletal sites, except LS. After segregation for VDR genotypes (40 bb, 47 Bb, and 14 BB), a significant calcium effect was present in Bb but not bb girls, whereas in BB girls there was a positive but nonsignificant trend for a calcium effect. Moreover, dietary calcium intake was significantly correlated with BMD changes at various independent bone sites in Bb girls but not in bb girls. In contrast, BMD gain in bb girls appeared to be higher than among the other genotypes when the dietary calcium intake was low, i.e., in the absence of calcium supplements. BMD was significantly associated with VDR gene polymorphisms only before puberty, BB girls having significantly lower BMD (Z scores) than the other genotypes. By increasing dietary calcium intake, BMD accrual was increased in Bb and possibly BB prepubertal girls, whereas bb subjects had the highest spontaneous BMD accrual and remained unaffected by calcium supplements. Taking into account complex interactions between VDR gene polymorphisms and environmental factors, including calcium intake, may thus help to understand the discordant relationships between BMD and VDR gene polymorphisms.

Adolescent↗
PubMed1998

Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3'-end region polymorphisms.

Osteoporosis is a polygenic disease, whose determining loci have not yet been identified. Vitamin D receptor (VDR) gene polymorphisms in the 3'-end region (as determined by the enzymes BsmI and ApaI) have been inconsistently associated with bone mineral mass. More recently, VDR start codon polymorphisms (as determined by the enzyme FokI) have been found to be related to adult bone mineral density (BMD) in pre- and postmenopausal American women. We investigated the association between BMD and FokI genotypes in premenopausal European-Caucasian women as well as in prepubertal girls from the same genetic background and examined the interaction with VDR 3'-end region polymorphisms and with dietary calcium intake. Areal BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at the level of the lumbar spine, femoral neck, and femoral shaft in 177 healthy premenopausal women (age range, 18.7-56.0 years) as well as in 155 prepubertal girls (age range, 6.6-11.4 years). Genotyping for FokI, BsmI, and ApaI VDR polymorphisms was performed using polymerase chain reaction methods. FokI genotype-dietary calcium interaction was cross-sectionally analyzed in all subjects and longitudinally in 103 prepubertal girls enrolled in a calcium intervention trial. The prevalence of FokI VDR gene polymorphisms in this cohort was 15% for ff, 50% for Ff, and 35% for FF. In the whole cohort of premenopausal women or prepubertal girls, no significant association was found between FokI VDR gene polymorphisms and BMD, even adjusted for age (Z score), weight, height, and calcium intake. Further analysis of FokI VDR gene polymorphisms and dietary calcium intake suggested a possible interaction in BMD determination, since a trend for an association with FokI genotypes was more evident at high than low calcium intake in both cross-sectional and longitudinal studies. Furthermore, cross-genotyping FokI and either BsmI or ApaI VDR polymorphisms suggested that the ff genotype was associated with a significantly lower lumbar spine BMD in bb and aa prepubertal girls. FokI VDR gene polymorphisms were not significantly associated with BMD in healthy European-Caucasian females. However, cross-genotyping of the VDR 3'-end and start codon polymorphic regions may provide a further insight into the complex determination of BMD.

Absorptiometry, Photon↗
PubMed1998

Immunocytochemical discrimination between early and late S phase: a new approach to the study of gingival epithelium proliferation in rats.

The renewal of the free gingival margin epithelium in rats was studied evaluating 5-bromodeoxyuridine (BrdU) incorporation in proliferating cells by means of an immunocytochemical method. We found a close correspondence between light and electron microscopy patterns of BrdU incorporation at a nuclear level. BrdU was localized in the inner interchromatin regions in cells starting DNA synthesis, while it was localized in the peripheral heterochromatin domains in cells terminating the S phase. This possibility of discriminating cells in early S phase from cells in late S is able to provide far more information as to the time at which a labeled cell starts proliferation than that obtainable with 3H-thymidine autoradiography. This, in turn, permits detection of cells that start proliferation in a wide period of time by means of a single BrdU administration. Rats treated at 7 a.m. demonstrated higher proliferation than rats treated at 7 p.m., supporting the existence of circadian variations in the epithelial renewal. Proliferative events take place by consecutive activation of at least three replication waves, producing clusters of labeled cells which could be observed in rats sacrificed at 10 a.m. In rats treated once with BrdU at 7 a.m., the clusters were localized in both the basal and suprabasal layer of the epithelium; in rats further injected with BrdU at the same time, the clusters increased in size, progressively extending throughout the epithelium. In this way, the renewal of the free gingival margin epithelium does not proceed randomly, but by consecutive activation of discrete units or clusters of basal cells, which then extend to the upper layers. This can be followed at a morphological level as a progression of labeled cells, which move from the basal layer to the epithelium surface in approximately 82-85 hours.

Animals↗