Variation in spinal and femoral bone mass gain, energy and calcium intake during adolescence.
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Adolescent↗
Biomedical subjects
R Rizzoli
Publications and source records attributed to R Rizzoli.
Relationship between bone mineral density and dietary intakes in the elderly.
Dietary protein and/or calorie insufficiencies represent an important problem in elderly patients. The biological and clinical implications, and particularly the influence on bone mass of undernutrition in the elderly, have not been completely defined, although several studies have demonstrated a high prevalence of dietary insufficiencies in patients with a recent fracture of the proximal femur. In the present study the relationship between dietary intakes, physical performance and bone mineral density (BMD) was examined in hospitalized elderly patients. The study comprised 74 patients (48 women, mean age 82 years; and 26 men, mean age 80 years) who were hospitalized for various medical indications. They were divided into two groups according to their dietary protein intakes, evaluated during the first 28 days in hospital while on a regular diet. The first group consisted of 26 patients (14 women and 12 men) whose protein intake was equal to or greater than 1 g per kilogram of ideal body weight. The second group consisted of 48 patients (34 women and 14 men) who consumed less than 1 g of protein per kilogram of ideal body weight. The two groups differed also in their energy, carbohydrate, lipid and calcium intakes. Patients in the group with the higher protein intake displayed higher BMD at the level of the femoral neck as measured by dual-photon absorptiometry. The men in this group also had higher lumbar spine BMD. After 4 weeks in hospital the women with a higher protein intake had significantly enhanced bicipital and quadricipital muscle strength and better performance as indicated by the increased capacity to climb stairs.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Parathyroid hormone-related protein increases cAMP production in mammary epithelial cells.
Parathyroid hormone-related protein (PTHrP) is a major cause of malignant hypercalcemia but has been found in many nontumoral tissues as well. Thus it is produced by the mammary gland during lactation and released into milk. Whether PTHrP directly affects breast tissue is however not known. We investigated the effects of PTHrP on adenosine 3',5'-cyclic monophosphate (cAMP) production in primary cultures of mammary epithelial cells isolated from lactating rats. On the 7th day in culture, synthetic PTHrP-(1-34), recombinant (r) PTHrP-(1-108), and rPTHrP-(1-141) stimulated cAMP production in a concentration-dependent manner. Thus PTHrP-(1-34) induced a 1.92 +/- 0.04-fold stimulation of cAMP production (mean +/- SE, n = 5 separate experiments, P < 0.001). At the time of maximal responsiveness to PTHrP, a significant proportion of the cells was characterized by an elongated shape and a positive immunofluorescent staining for both prekeratin and alpha-smooth muscle actin 1, compatible with a myoepithelial phenotype. It therefore appears that PTHrP can stimulate the production of cAMP in mammary cells, suggesting a possible autocrine/paracrine regulatory function for PTHrP in breast tissue.
Animals↗
IGF-I and pamidronate increase bone mineral density in ovariectomized adult rats.
Effects induced by insulin-like growth factor I (IGF-I) and/or the bisphosphonate pamidronate (APD) on bone mineral density (BMD) of the lumbar spine and proximal and midshaft tibia were studied in adult rats made osteopenic by ovariectomy, using dual-energy X-ray absorptiometry. IGF-I, which was administered by osmotic minipumps implanted subcutaneously for 6 wk, caused a dose-dependent increase of BMD at the three investigated sites. A 4-wk course of IGF-I, followed by intermittent cyclical APD administration, induced significant increases of BMD at the levels of spine and proximal tibia. At midshaft tibia, where cortical bone predominates, BMD was increased by IGF-I only. In conclusion, IGF-I increased BMD at sites with trabecular and/or cortical bone, whereas the APD influence was mainly detectable in the former site only.
Absorptiometry, Photon↗
Transforming growth factor-beta inhibits phosphate transport in renal epithelial cells.
The effect(s) of transforming growth factor-beta (TGF-beta) on Pi transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium-dependent Pi, but not alanine, transport. This selective inhibitory effect on Pi transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in Pi uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated Pi transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced Pi transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Bone mineral density in patients with end-stage renal failure.
Renal osteodystrophy is a well-recognized complication of chronic renal failure (CRF) and is associated with a marked morbidity. Bone mineral density (BMD) has been shown to be the best predictor of fracture risk in different circumstances. In this cross-sectional study, we measured BMD using dual photon absorptiometry at three skeletal sites of functional importance such as the lumbar spine (LS), the femoral shaft (FS) and the femoral neck (FN) in 106 patients with end-stage renal failure (11 predialysis patients and 95 patients on maintenance dialysis). These skeletal sites are characterized by various relative amounts of trabecular and cortical bone. The results indicate that decreased bone mass was detectable in all skeletal sites before the beginning of dialysis and that BMD was negatively related to dialysis duration in LS and FS. Nevertheless, the deleterious effects of renal osteodystrophy were more pronounced at the FS level, where cortical bone is predominant. A separate analysis of BMD in both sexes revealed that females presented a more important bone loss in both cortical and trabecular bone than males. We did not find any significant difference in BMD at the three measured sites between patients on continuous ambulatory peritoneal dialysis and on regular hemodialysis. This study emphasizes the need to pay more attention to the prevention of bone loss in patients on CRF before the start of dialysis therapy, and to the fact that the female population might display a more pronounced susceptibility to bone loss.
Absorptiometry, Photon↗
Transforming growth factor-beta modulates the parathyroid hormone-related protein-induced responses in renal epithelial cells.
PTH-related protein (PTHrP), the major mediator of hypercalcemia of malignancy, reduces tubular phosphate (Pi) reabsorption through its PTH-like renotropic actions. Another peptide detected in tumoral cells, transforming growth factor-beta (TGF beta), has been shown to considerably suppress the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. The unexplored interactions between TGF beta and PTHrP were examined in opossum kidney (OK) cells. Using confluent OK cells, we showed that TGF beta attenuated the inhibition of Pi transport mediated by PTHrP. Similarly, 18 h TGF beta incubation resulted in a substantial reduction of the cAMP response elicited by PTHrP without apparent involvement of pertussis toxin-sensitive guanine nucleotide binding protein(s). The number of PTHrP(1-34) binding sites in TGF beta-treated cells was decreased with the affinity unchanged. Forskolin- and prostaglandin E2-stimulated cAMP productions were not significantly altered by TGF beta treatment. Therefore, TGF beta reduced Pi transport in OK cells, modulated the actions of PTHrP, and decreased its receptor number. Whether this happens in vivo is as yet unknown.
Animals↗
Decrease in nuclear phospholipids associated with DNA replication.
Lipid metabolism in nuclei is very active and appears involved in the transduction of signals to the genome in response to agonists acting at the plasma membrane level. However, the precise topology of nuclear lipid metabolism and the relationship between nuclear lipids and crucial events of the cell function, such as DNA replication, have not been fully elucidated. By using a recently developed cytochemical method for detecting phospholipids inside the nucleus of intact cells at the electron microscope level, we have analyzed the changes in intranuclear phospholipids in DNA-replicating versus resting cells, which are both present in the same sample of regenerating liver after partial hepatectomy. The pattern of DNA synthesis in replicating cells has been monitored by electron microscope immunocytochemistry after bromodeoxyuridine (BrdU) labeling. The data obtained, which allow a fine localization and a quantitative analysis of both DNA synthesis and phospholipid distribution, indicate a significant reduction in the phospholipids detectable inside the nucleus in all steps of the S phase. This could depend on an increased nuclear phospholipid hydrolysis, whose products should in turn activate some of the enzymes involved in the control of DNA replication.
Animals↗
Non-surgical treatment of primary hyperparathyroidism.
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Adenoma↗
Alterations of calcium and phosphate metabolism in primary hyperparathyroidism during pregnancy.
Primary hyperparathyroidism (PHP) is rare during pregnancy and has been claimed to be associated with significant increase of neonatal morbidity and mortality. Whether the well recognized changes in calcium (Ca) and phosphate (Pi) homeostasis occurring in pregnancy might influence the biochemical expression of PHP is unclear. We evaluated biochemical parameters of calcium and phosphate metabolism in two cases of PHP in pregnancy diagnosed in the third trimester (patient 1) and in the second trimester (patient 2). Both patients displayed increase in protein-adjusted plasma Ca, bone resorption evaluated by the fasting urinary Ca-to-creatinine ratio, renal tubular reabsorption of Ca, urinary cAMP excretion and decrease in renal tubular reabsorption of Pi. These alterations were identical to those found in 12 non-pregnant women with PHP. The biochemical expression of PHP did not change after delivery in patient 1. This patient underwent the excision of a 1 g parathyroid adenoma on the 13th day after delivery, which led to normalization of all biochemical parameters. The lowest plasma Ca of the newborn of patient 1 was 2.02 mM 72 hours after birth. Thus, the results indicate that these two pregnant women with PHP displayed biochemical alterations of calcium and phosphate metabolism similar to those observed in non-pregnant women with primary hyperparathyroidism.
Adult↗
Bisphosphonates and hypercalcemia.
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Child↗
Proliferative response of human marginal gingiva to phlogistic process and titanium implant.
In order to detect proliferative processes in human marginal gingiva in pathological conditions and after externalization of titanium implants, we have attempted BrdU incorporation after "in vitro" incubation of tissue fragments. In comparison with healthy controls, immunocytochemical detection of samples from patients affected by hypertrophic gengivitis shows a good number of proliferating cells in the basal layer of the epithelium, while only in one case can positiveness be detected after externalization of titanium implants. Since after reduction of inflammation by hygienic treatment a low number of proliferating cells can be observed only in the regions where pathological alterations are also present, we suggest that the increase in tissue proliferation may be closely dependent on the intensity of the inflammatory process. All these data demonstrate that in vitro BrdU incubation of tissue fragments represents a suitable method to evaluate cell proliferation in human tissue.
Adult↗
Bromodeoxyuridine incorporation in corneal epithelium: an immunocytochemical study in rats.
Here we investigate the kinetics of rat corneal epithelium at both single cell and tissue level by means of a BrdU-anti BrdU method. The results obtained have then been compared with those previously obtained by us in rat vocal cord epithelium. In this way two main aspects of BrdU incorporation can be indicated at both light and electron microscopy level. First, we report evidence of a new incorporation pattern corresponding to middle S phase, which is characterized by labelling distribution at the border between interchromatin and heterochromatin at ultrastructural level. Second, by comparing tissue incorporation in rats treated with BrdU at the beginning of light time and at the beginning of dark time, we show an increase of cell proliferation during the last hours of dark time and the first hours of light time. In this way, we demonstrate a different progression of circadian rhythms in peripheral regions of corneal epithelium in comparison with that previously observed in vocal cord epithelium.
Animals↗
[Eating behavior and bone mineral density in young women marathon participants].
Although reduced gonadal steroid hormone concentration appear to play a major role in lower trabecular bone density (BMD) in female marathon runners, dietary deficiencies and eating behaviors may also affect BMD. To investigate that possibility, dietary patterns and BMD were examined in 27 female regular marathon runners classified as eumenorrheic (8), amenorrheic (10) and under oral contraception (9). The results show a significant lower BMD in amenorrheic athletes but no dietary deficiencies. These results suggest that the eating behavior don't play any role in the lower BMD of our athletes.
Adolescent↗
[Bone mineral density of the lumbar spine, the femoral neck and femoral diaphysis in a Genevan population sample].
Bone mineral density (BMD) was measured by dual photon absorptiometry in the lumbar spine, femoral neck and midfemoral shaft in 209 women and 165 men aged 20 to 98 years recruited among the Geneva population. The prevalence of various factors (life style, calcium intake, body weight) which may be associated with a higher risk of osteoporosis was evaluated. Between the different skeletal sites, BMD was closely correlated. Nevertheless, BMD at one site failed to accurately predict BMD of another site. In each age class, BMD was dispersed over a wide range. Women and men had similar lumbar spine BMD. In women, BMD decreased after the fifth decade by 1.3, 1.0 and 2.6% year in the lumbar spine and femoral neck and shaft, respectively. Daily calcium intake from dairy products was 430 g and 750 g in women and men, respectively. Femoral shaft BMD was positively correlated with calcium intake. These BMD values obtained in a sample of the normal Geneva population should be of major help for the diagnosis of osteoporosis.
Adult↗
Effect of a single infusion of alendronate in malignant hypercalcaemia: dose dependency and comparison with clodronate.
Among aminohydroxybisphosphonate derivatives, alendronate (3-amino-1-hydroxybutylidene-1,1-bisphosphonate) has proved efficacious in diseases with increased bone resorption. However, the effective dose in the treatment of malignant hypercalcemia is not clearly established. In 2 randomized studies, we investigated the effects of alendronate and of clodronate (dichloromethylene bisphosphonate) given as a single infusion in 82 rehydrated patients with malignant hypercalcaemia. Various doses of alendronate or clodronate soon produced a significant fall in plasma calcium (Ca), accompanied by a dose-dependent decrease in the fasting urinary Ca/creatinine ratio, taken as a reflection of bone resorption. During the next 5 days, plasma Ca and fasting urinary Ca/creatinine ratio were lower in the group treated with alendronate than in the clodronate group. The renal handling of Ca was similar in both groups. Because of relapsing hypercalcaemia, some patients received an infusion of alendronate approximately 2 weeks after the first infusion; this normalized the urinary Ca/creatinine ratio in 44% of the cases at day 3. At that time, the plasma Ca was below 2.70 mmol/l in 33%. Our results indicate that alendronate decreased bone resorption and calcaemia in cancer patients in a dose-dependent manner.
Aged↗
Sequential and precise in vivo measurement of bone mineral density in rats using dual-energy x-ray absorptiometry.
In the design of new strategies for the treatment of osteoporosis, noninvasive, precise, and sensitive bone mass measurement capable of detecting changes over short periods of time in small animals is essential. Most of the models described thus far require the sacrifice of the animals and/or display low reproducibility. Using a dual-energy x-ray absorptiometer (DEXA; Hologic QDR-1000) in an ultrahigh-resolution mode, we measured bone mineral density (BMD) in rats at the levels of lumbar spine (L1-4), proximal tail (caudal vertebrae C2-4), and tibia. Accuracy was evaluated by measuring the mineral content of bone powder capsules (within the range of rat vertebrae BMD), under 0.5-3 cm water to mimic variations in soft tissue thickness. The bone powder capsule mineral content was highly correlated with chemically determined hydroxyapatite content (r = 0.999). In vivo reproducibility was evaluated by calculating the coefficient of variation (CV = 100 x SD/mean) of four to six BMD measurements, each time with repositioning, in seven rats (220-500 g body weight). CV was 1.36 +/- 0.32% (x +/- SD) for lumbar spine, 0.66 +/- 0.50% for proximal tail, and 1.12 +/- 0.45% for tibia. The ability to detect BMD changes was investigated by measuring BMD before and every 4 weeks after ovariectomy (OVX) in 270 g rats, pair fed during the whole experiment. Compared with sham-operated control animals, a highly significant difference in lumbar spine BMD was observed 4 weeks after OVX, which reached a maximum by 8 weeks and remained stable thereafter. At the level of the proximal tibia, the difference was maximal 4 weeks after OVX.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Parathyroid hormone-related protein production by primary cultures of mammary epithelial cells.
Parathyroid hormone-related protein (PTHrP) plays a major role in the pathogenesis of malignant hypercalcemia, but has also been found in fetal and adult non-neoplastic tissues. Among them, lactating mammary gland was shown to produce PTHrP, and high levels of PTHrP were measured in milk. However, the regulation of PTHrP production by breast cells is still unknown. Primary cultures of mammary cells isolated from rat lactating glands were grown on collagen gels in an insulin/epidermal growth factor (EGF)-supplemented medium. Under these conditions, mammary cells displayed an epithelial phenotype and their number increased more than twofold after 1 week in culture. At that time, the cells were capable of producing immunoreactive PTHrP (range: 25 to 150 pg/10(5) cells x 24 h) and PTH-like bioactivity, as indicated by a 60% increase in cyclic adenosine monophosphate (cAMP) production induced by mammary epithelial cell conditioned medium in the PTH-responsive osteoblast-like UMR-106 cell line. When cell proliferation was hindered by lowering plating density, by removing medium supplements, or by adding transforming growth factor (TGF)-beta, a well-known autocrine inhibitor of mammary epithelial cell growth. PTHrP production was increased. In contrast, the omission of EGF or addition of specified anti-EGF antibodies decreased PTHrP production. In conclusion, primary cultures of mammary epithelial cells isolated from lactating rat were shown for the first time to produce PTHrP in vitro. This production was higher in the presence of EGF and could be modulated by cell growth rate.
Animals↗