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Biomedical subjects

R Rizzoli

Publications and source records attributed to R Rizzoli.

At least 19 recordsLinked to original sources
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

DNA synthesis progression in 3T3 synchronized fibroblasts: a high resolution approach.

In order to investigate at ultrastructural level the mechanism of DNA synthesis progression during the different moments of S-phase a bromodeoxyuridine-anti bromodeoxyuridine (BrdU-anti BrdU) method has been applied to synchronized 3T3 fibroblasts. After 30 min BrdU incorporation, five different labelling patterns can be identified and should be related to early, middle and late S-phase. These patterns are represented mainly by diffuse labelling localized in different nuclear domains and by quite rare cases in which the labelling is limited to isolated clusters of gold particles. After a 5-min pulse with BrdU it is possible to observe isolated clusters of gold particles at each moment of S-phase, which, however, exhibit the same distribution of the five principal labelling patterns observed after 30 min incorporation. In both cases labelling can be detected in the interchromatin regions during early S-phase, at the boundary between interchromatin and heterochromatin during middle S-phase and in the heterochromatin domains during late S-phase. Considering their size, the isolated spots of labelling could be interpreted as single replication units which are subsequently activated throughout the different moments of the S-phase.

3T3 Cells↗
PubMed1992

Effect of intraduodenal administration of 23-methyl-UDCA diastereoisomers on bile flow in hamsters.

3 alpha,7 beta-Dihydroxy-23-methyl-5 beta-cholan-24-oic acid (MUDCA) and its two diastereoisomers, alpha- and beta-MUDCA, were infused intraduodenally in biliary fistula hamsters in order to evaluate the effect on bile flow and their hepatic biotransformation processes compared with the natural analog ursodeoxycholic acid (UDCA). In addition, the corresponding glycine conjugates were compared. The bile acids were administered at different doses (0.7-6 mumol/min/kg) over periods of 90 min. The results indicate that the racemic mixture exhibits a potent choleretic effect at both low and high doses, while the two individual diastereoisomers show this effect only at high doses. The presence of a C-23 methyl group in the side chain prevents hepatic amidation and alternative conjugations occur, such as glucuronidation, in order to facilitate their biliary secretion. Biotransformation of the methyl derivatives of UDCA occurred mainly by conversion to more polar glucuronide conjugates. There was little alteration to the molecule and, unlike UDCA, very little amidation occurred. These data indicate that the presence of a C-23 methyl group prevents the usual side-chain amidation common to the most naturally occurring bile acids and that glucuronidation is a requisite for efficient biliary excretion.

Acute Disease↗
PubMed1992

Morphological evidence of function-related localization of phospholipids in the cell nucleus.

The evidence accumulated in recent years on the presence of phospholipids inside the interphase nucleus needs a precise localization of the nuclear sites of accumulation, transport and degradation of these molecules. A very useful approach for monitoring the fine localization of nuclear phospholipids is represented by a recently developed technique using gold-conjugated phospholipases. In fact, in addition to the phospholipids organized in bilayers in the membrane, this technique identifies amorphous lipoprotein complexes present in different cell areas as well as in the nucleus. In this way and using sample preparation systems which reduce lipid removal and translocation, such as cryofixation, cryosectioning, embedding in hydrophylic resins and cryofracturing, we have analyzed the subnuclear localization of phospholipids in different experimental conditions. The results indicate that: in interphase the nuclear phospholipids are localized mainly in the interchromatin spaces and in the nucleolar domain; the observed co-localization of phospholipids and ribonucleoproteins suggests that phospholipids are involved in the mechanism of transport and release of the transcripts; the demonstrated release of ribonucleoproteins after phospholipase digestion suggests that phospholipids mediate the binding between ribonucleoproteins and the nuclear matrix; significant changes of the phospholipid localization occur in the different phases of the cell cycle or in the course of induced cell differentiation.

Animals↗
PubMed1992

Comparison of a rapid (2-h) versus a slow (24-h) infusion of alendronate in the treatment of hypercalcemia of malignancy.

Alendronate (aminohydroxybutylidene bisphosphonate) is a potent inhibitor of bone resorption but the role of the duration of intravenous infusion in its efficacy profile is unclear. In a two-centre, parallel, randomized, double-blind study, 20 patients with tumoral hypercalcemia received a single 10-mg i.v. infusion over either 2 h (group A, n = 10) or 24 h (group B, n = 10). Recurrences (n = 6) were retreated using the same regimen. Pretreatment plasma calcium (Ca) was 3.32 +/- 0.08 mM (mean +/- SEM) for all patients. Treatment A and B were associated with similar temporal profiles for onset, time to reach normocalcemia, (6 vs 5 days), nadir (day 6: 2.45 +/- 0.06 vs 2.43 +/- 0.08 mM) and time to relapse (day 21). Normocalcemia (2.15-2.55 mM) was achieved in seven (A) and nine (B) patients with other cases being partial responders (Ca: 2.65-2.76 mM). A significant decrease of urinary calcium and hydroxyproline excretion and a significant increase of PTH accompanied Ca normalization in both groups. Ca response was 50% lower on 2nd treatment with alendronate. Both treatments were well tolerated with transient mild fever being the most common adverse experience. In conclusion, whether infused over 2 or over 24 h, a single dose of 10 mg alendronate led to normalization of tumoral hypercalcemia in a large majority of cases.

Aged↗
PubMed1992

Inhibition of bone resorption by the bisphosphonate BM 21.0955 is not associated with an alteration of the renal handling of calcium in rats infused with parathyroid hormone-related protein.

Hypercalcaemia of malignancy is determined by an increase of bone resorption and/or renal tubular reabsorption of calcium (Ca). However, this latter component has been found to vary in certain patients during therapy with bone resorption inhibitors such as bisphosphonates. We investigated the possible effects of the highly potent bisphosphonate BM 21.0955 on the renal handling of Ca in thyroparathyroidectomized rats made hypercalcaemic by the stimulation of both bone resorption and renal tubular reabsorption of Ca induced by the chronic infusion of parathyroid hormone-related protein (PTHrP). Dose-dependent inhibition of bone resorption by BM 21.0955, as indicated by the decrease in fasting urinary Ca excretion from 64.0 +/- 7.3 to 6.7 +/- 3.1 nmol/ml GFR, was associated with a change in plasma Ca from 2.97 +/- 0.10 to 2.63 +/- 0.16 mmol/l. However, the relationship between urinary Ca excretion and plasma Ca was not altered, either at endogenous plasma Ca concentration or during the acute infusion of Ca. Similarly, an index of renal tubular reabsorption of Ca calculated from the slope of the linear portion of the relationship between urinary Ca and plasma Ca, which was increased by PTHrP administration, was not influenced by BM 21.0955 therapy (2.59 +/- 0.15 vs. 2.55 +/- 0.11 mmol/l GFR). These results indicate that BM 21.0955, which is one of the most potent bisphosphonates inhibiting bone resorption, did not affect the renal tubular reabsorption of Ca enhanced by PTHrP.

Absorption↗
PubMed1992

Management of disorders of calcium homoeostasis.

Severe hypercalcaemia may be life-threatening and requires prompt management. Whatever the cause, the aim of therapy should obviously be to eradicate the source of hypercalcaemic factors. After rehydration, which is an essential first step in the management strategy, and after evaluation of the prevailing pathogenetic mechanism, the acute treatment will be aimed at increasing urinary Ca excretion and inhibiting bone resorption. Among the various pharmacological agents, bisphosphonates appear to be the drugs of first choice, because of their efficacy and their virtual absence of side-effects. The decision to treat hypocalcaemia is determined by the extent of the symptoms and the risk of complications. The treatment of acute hypocalcaemia comprises the parenteral administration of Ca or magnesium, when magnesium deficiency can be suspected. Then, chronic hypocalcaemia may require the use of 1,25-dihydroxyvitamin D, once the replenishments of vitamin D stores have been assured.

Acute Disease↗
PubMed1992

Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur.

Malnutrition has been often suggested as contributing to both the high incidence of hip fracture in elderly people and its complications. In a recent prospective controlled randomized study, the clinical outcome of elderly patients with osteoporotic fracture of the proximal femur (hip fracture) improved by giving a simple oral dietary supplement. This study, however, did not prove that protein was responsible for the clinical improvement since the supplement also contained vitamins and minerals. We addressed this question by comparing the clinical outcome and bone mineral density (BMD) changes in elderly patients with hip fracture, receiving two different dietary supplements with different protein contents. Sixty-two patients (mean age 82) admitted into the orthopedic ward for fracture of the proximal femur were randomized into two groups. One group (n = 33) received 250 ml/day of an oral nutritional supplement containing protein (20.4 g), mineral salts (Ca: 0.525 g) and vitamins A = 750 IU; D3 = 25 IU) for a mean of 38 days. A control group (n = 29) received the same supplement dose, but with no protein, for the same period of time. The clinical course was significantly better in the group receiving protein, with 79% having a favorable course as compared to 36% (p less than 0.02) in the control group during the stay in the recovery hospital. The rate of complications and deaths was also significantly lower in the protein-supplemented vs the control group (52 vs 80%, p less than 0.05) 7 months after hip fracture. The median hospital stay was significantly lower in the protein-supplemented group (69 vs 102 days, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Assessment of whole-body composition with dual-energy x-ray absorptiometry.

Dual-energy x-ray absorptiometry (DXA) allows noninvasive direct measurement of the three major components of body composition: lean body mass (LBM), fat body mass (FBM), and bone mineral body mass (BBM). To study the accuracy and short-term and long-term precision of body composition measurements, the authors measured body composition with DXA in 60 healthy young adults. Independent measurement of LBM (LBMK-40), obtained from the determination of the whole-body content of potassium-40 with a whole-body scintillation detector, was highly correlated with LBM determined with DXA (LBMDXA) (LBMK-40 = 1.069.LBMDXA,R2 = .996). Assessment of body composition in 10 patients with acquired immunodeficiency syndrome (AIDS) and 10 patients with cystic fibrosis was performed with DXA. The AIDS patients showed a marked decrease in LBM, while in patients with cystic fibrosis, LBM and BBM were decreased. DXA measurements of body composition appeared accurate and precise enough to be of clinical relevance in detecting specific alterations of body composition.

Absorptiometry, Photon↗
PubMed1992

Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects.

The amount of skeletal mass acquired during adolescence is one of the most important determinants for the risk of postmenopausal and involutional osteoporosis. In both sexes, a large variance in bone mineral density (BMD) and content (BMC) is observed among healthy individuals at the beginning of the third decade. To determine the crucial pubertal years during which bone mass accumulation mainly occurs, we longitudinally monitored the gain in BMD/BMC at clinically important sites, such as lumbar spine and femoral neck, with respect to osteoporotic fracture risk. The changes in BMD (grams per cm2) and BMC (grams) were determined at 1-yr intervals at the level of lumbar spine vertebrae (L2-L4), femoral neck, and midfemoral shaft, using dual energy x-ray absorptiometry (Hologic QDR 1000), in 198 healthy adolescents (98 females and 100 males), aged 9-19 yr. Mean daily energy and calcium intakes, height, weight, and body mass index of the studied cohort were within the normal range for age. In females, the increment rate in BMD/BMC was particularly pronounced over a 3-yr period, i.e. from 11-14 yr of age. This increment dramatically fell after 16 yr and/or 2 yr after menarche. The mean gains in lumbar, femoral neck, and midfemoral shaft BMD were not statistically significant between 17-20 yr. In males, the gain in BMD/BMC was particularly high over a 4-yr period, i.e. from 13-17 yr. Then the increment rate markedly declined, but remained significant between 17-20 yr for L2-L4 BMD/BMC and midfemoral shaft BMD. In contrast, no significant increase was observed for femoral neck BMD. An impressive interindividual variation was observed between the yearly height increment and the bone mass accumulation. The bone mass-height gains relationship during puberty evolved according to a loop pattern, with maximal variance at Tanner stages P3-P4. This longitudinal study delineates the crucial pubertal years during which the skeletal mass accumulates at high, but various, rates at skeletal sites where the consequences of the osteoporosis are particularly dramatic. Furthermore, the results indicate that in a cohort of healthy females with apparently adequate intakes of energy and calcium, bone mass accumulation is drastically reduced by 16 yr of age in both lumbar spine and femoral neck.

Absorptiometry, Photon↗
PubMed1992

Actions of parathyroid hormone and parathyroid hormone-related protein.

By interacting with a structurally identical receptor, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) display a common spectrum of action on the transport of mineral elements in bone and kidney. In vivo, PTH/PTHrP similarly reduce the renal tubular reabsorption of inorganic phosphate (Pi) and increase that of calcium. The hypercalcemic effect of PTHrP is due to an increase in both bone resorption and renal calcium reabsorption, the latter through a sodium-independent mechanism. The PTHrP-stimulated bone resorption can be totally inhibited by bisphosphonate therapy. Despite that, the fall in calcemia is moderate, indicating that the PTHrP main hypercalcemic action is due to the stimulation of the renal transport of calcium. For identical effects on renal ionic transports, PTHrP appears to less stimulate bone formation than PTH. These experimental findings are similar to clinical observations in patients with primary hyperparathyroidism or with solid malignant tumors. In vitro, the effects of PTH(1-34), PTHrP(1-34) and PTHrP(1-141) on cAMP production and sodium-dependent phosphate transport (NaPiT) are similar in kidney cells, where NaPiT is specifically inhibited by either peptide. This effect is attenuated by the competitive inhibitor [D-Trp12,Tyr34]bPTH(7-34)amide. Transforming growth factor-alpha similarly modulates the cAMP and NaPiT responses to PTH/PTHrP. In cultured mammary cells isolated from lactating rats, PTHrP elicits a 2-fold increase of cAMP production. Various products of bone and stromal cells, and of leukocytes, such as Interleukin-6 or Tumor necrosis factor-alpha, as well as high extracellular calcium concentration enhance PTHrP production by cultured lung squamous cell carcinoma and Leydig tumor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Parathyroid hormone binding to cultured avian osteoclasts.

Parathyroid hormone (PTH) increases serum calcium concentration via a controversial cellular mechanism. We investigated whether PTH binds avian osteoclasts. Isolated hypocalcaemic hen osteoclasts were incubated with [125I]--bovine PTH (1-84). Specific binding of the hormone to the cells, which reached the equilibrium within 60 min, was observed. Half maximal binding was reached by 10 min. Binding was competitively inhibited by increasing doses of unlabeled PTH, and was about 55% displaced by adding, at the equilibrium, 10(-6) M unlabeled PTH. Autoradiography demonstrated specific label on the osteoclast. The cellular mechanism activated by the hormone remains to be elucidated.

Animals↗
PubMed1991

Stimulation by parathyroid hormone-related protein and transforming growth factor-alpha of phosphate transport in osteoblast-like cells.

Parathyroid hormone (1-34) [PTH-(1-34)] has been shown to stimulate sodium-dependent phosphate transport (NaPiT) in UMR-106 osteoblast-like cells through a cAMP-dependent mechanism. Whether a synthetic amino-terminal fragment of parathyroid hormone-related protein (PTHrP) or the full-length molecule, which are recognized to interact with the same receptor as PTH, affect NaPiT in the same way is not known. We investigated and compared the effects of bPTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) on NaPiT and cAMP production in the osteoblastic cell line UMR-106. Each of the three peptides increased cAMP production and exerted a concentration-dependent stimulation of NaPiT after incubation for 4-6 h. We also studied the effect of transforming growth factor-alpha (TGF-alpha), which is another tumoral product secreted by certain hypercalcemia-associated tumors, on NaPiT and the TGF-alpha-induced modulation of the response to PTHrP or PTH. TGF-alpha caused a 30% stimulation of NaPiT, which remained stable from 6 to 24 h, by a cAMP-independent mechanism. In contrast, TGF-alpha attenuated cAMP production stimulated by PTH, PTHrP-(1-34), or PTHrP-(1-141). PTHrP or PTH did not further increase NaPiT in TGF-alpha-treated cells. These results indicate that NaPiT, a possibly important function of osteoblastic cells, was similarly affected by PTH and PTHrP. TGF-alpha increased NaPiT and modulated in a similar way the effects of both PTH and PTHrP.

Alanine↗