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C Gennari

Publications and source records attributed to C Gennari.

At least 127 records · Page 7Linked to original sources
PubMed1993

Bone endothelial cells as estrogen targets.

In the present study, we investigated the effects of estrogens on bone endothelial cell metabolism and the presence of estrogen binding sites in the same cells. For these studies, we have used a continuous cell line of clonal bovine bone endothelial cells for evidence of a direct response to estrogens in vitro. Receptor analysis to intact viable cells was steroid specific and saturable, with an apparent dissociation constant of 17.2 nM and a Bmax of 3.2 x 10(4) sites/cell. Northern blot analysis revealed a 6.5-kilobase mRNA that hybridized with a cDNA to human estrogen receptor. The 6.5-kilobase size is in close agreement with the reported size of the human estrogen receptor mRNA. In vitro estrogen responses of bone endothelial cells included a stimulation of cell proliferation as well as an inhibition of parathyroid hormone responsiveness. These findings clearly demonstrate the presence of functional estrogen receptors in bone endothelial cells in vitro, suggesting a role of estrogens in bone angiogenesis and in the entire process of bone remodeling.

Animals↗
PubMed1993

Trends in the incidence of hip fracture in Siena, Italy, from 1980 to 1991.

There is general agreement that the crude incidence of proximal femur (hip) fractures is rising in conjunction with the ageing of the underlying population. To explore possible changes in hip fracture incidence over time we analysed all femoral fractures occurring in the county of Siena from 1980 to 1991. Data were collected from hospital record charts of the Department of Orthopaedics, recording all hip fractures occurring during the 12-year period. In this period, the mean resident population in Siena was 238,369 inhabitants (aged 0 to 90+ years) and the crude number of all femoral fractures was 2,238. However, in calculating incidence rates, only hip fractures occurring in the population aged over 50 years were considered. In this population, the number of hip fractures was 1,825 with a male/female ratio of 1:2.8. A time-series data analysis (temporal trend) of the incidence of hip fracture during the 12-year period revealed a linear and significant (p < 0.001) trend to increase, but only in males, with an annual increasing rate of 3.62 per 100,000 person-years. In the female population, the temporal analysis did not show any significant trend during the observation period.

Adolescent↗
PubMed1993

Hip fracture in Italy: epidemiology and preventive efficacy of bone-active drugs.

In this paper we report the results on the epidemiology of hip fracture and the preventive efficacy of bone-active drugs in Italy, observed in men and women aged 50 years or over, recruited in the three Italian centres participating in the Mediterranean Osteoporosis Study (MEDOS), namely Parma, Rome, and Siena. The number of fractures observed was 1,437 in a catchment area population of 847,508 individuals, with a total incidence of 169.6/100,000--a female-to-male ratio of 3.5 and a doubling-time of about 5.5 years. The female excess becomes evident in the age groups over 60 years. The mean age of fractures was 77 years in females and 73 in males. From the data collected, the estimated number of fractures per year in the Italian population aged over 50 years is 32,000. The pattern of use and the preventive efficacy of bone-active drugs was examined in women. Calcitonin and calcium were the drugs mainly used; less than 3% had taken vitamin D or oestrogen and only a minor percentage had taken anabolic steroids. Fluorides were not used at all. As seen in the European sample, the protective effect of calcium and calcitonin is statistically significant even in Italy, while vitamin D is not. The use of anabolic steroids was associated with a decrease in risk. Oestrogen administration does not seem to reduce the relative risk of hip fracture in Italian women, probably due to the small sample size.

Aged↗
PubMed1993

Long-term treatment with calcitonin in osteoporosis.

Many studies have shown that calcitonin has beneficial effects on the clinical and biological disturbances of diseases characterized by an excessive bone remodelling. Several controlled clinical studies have shown that long-term calcitonin treatment, given by parenteral or intranasal routes, exerts a beneficial positive effect on bone mass and bone turnover in established postmenopausal osteoporosis. Calcitonin therapy is particularly indicated for patients with high turnover osteoporosis where results show a net gain of bone mineral in the axial skeleton and a slowing of bone loss in the appendicular bones. Recently, calcitonin was shown to induce a significant reduction in postmenopausal osteoporotic vertebral fractures. Due to receptor down-regulation a resistance to the hormone may occur after 12-18 months of continuous treatment. Reported results of long-term calcitonin treatment demonstrated that it is possible to delay or to avoid the "resistance" to calcitonin by the cyclical or discontinued administration of the hormone.

Bone and Bones↗
PubMed1993

Differential effect of glucocorticoids on calcium absorption and bone mass.

Osteoporosis is one of the most serious side effects of glucocorticoid therapy and its development and severity are dependent on the particular glucocorticoid used. A short-term study (15 days) comparing the bone wasting effects and changes in calcium absorption induced by equiactive low and high doses of prednisone, deflazacort (DFZ) and betamethasone, revealed that low and high doses of betamethasone and high doses of prednisone induced a significant decrease in intestinal calcium absorption. No such changes were observed with DFZ. As 1,25-dihydroxycholecalciferol levels were maintained throughout the study, it appears that glucocorticoids impair calcium absorption through a mechanism not involving this hormone. A long-term study (1 year) of equipotent doses showed that all three glucocorticoids caused a decrease in calcium absorption and a progressive decrease in lumbar spine bone mineral content. However, the impairment of calcium absorption and decrease in bone mineral content was least with DFZ. Thus, DFZ appears to offer a degree of protection against both decreased calcium absorption and bone loss.

Adult↗
PubMed1993

[The evaluation of the antiarrhythmic activity of L-carnitine and propafenone in ischemic cardiopathy].

In order to evaluate a possible antiarrhythmic action of L-carnitine (C) in ischemic heart disease, 30 patients (20 males, 10 females, average age 64 years +/- 11) with ischemic heart disease who at examination with 24-hour dynamic ECG showed extrasystolic ventricular multifocal arrhythmia with a mean hourly rate of > 300 were randomized into three groups, the first of which was given a daily oral dose of 6 g C in three divided doses; groups 2 and 3 were given propafenone (P), 900 mg daily in three divided doses. After one week, all patients were again submitted to 24-hour dynamic ECG after which treatment was continued for another week as follows: group 1 continued on C (6 g daily), group 2 continued on P (900 mg daily), group 3 continued on P (900 mg daily) plus C (6 g daily). At the end of the second week, a further 24-hour ECG was performed the results of which showed that L-carnitine can significantly reduce the antiarrhythmic activity of the ischemic myocardium. In addition, at the end of the second week, a further significant reduction of the number of premature beats compared to the first week was found in patients for whom L-carnitine had been added to propafenone treatment.

Aged↗
PubMed1993

[Role of aldosterone in essential arterial hypertension complicated by chronic renal insufficiency].

The following parameters were studied in a group of patients suffering from essential arterial hypertension complicated by chronic renal insufficiency (CRI), mean age = 64.31 +/- 1.84, with creatinine clearance (CrC) ranging between 30 and 60 ml/min: blood pressure (systolic and diastolic arterial pressure), heart rate, plasmatic renin activity (PRA), plasma levels of aldosterone (ALDO) both in clino- and orthostatism, as well as some metabolic parameters. All parameters were compared with those in a group of age- and sex-matched patients with slight or moderate essential arterial hypertension. Before starting the study all patients completed a wash-out period of one week to annual the effects of other drugs which might interfere with the RAA system. PRA levels were within the norm, whereas plasma levels of ALDO were high both in clino- and orthostatism. ALDO levels were also found to be inversely correlated with those of CrC. From these data it emerges that hyperaldosteronism, as observed in these patients with CRI, is a relatively reliable marker of the extent of CRI and may occur independently of the activation of the RAA system, given that other factors, such as orthostatic stimulation, alterations in the acid-base equilibrium, and the degree of aldosterone hepatic and urinary clearance, contribute to its pathogenesis.

Adrenocorticotropic Hormone↗
PubMed1993

[Age-related changes in the renin-angiotensin-aldosterone system and the sympathetic nervous system in patients with essential hypertension].

The aim of this study was to evaluate age, plasmatic renin activity (PRA), plasma aldosterone levels and the total quantity of urinary catecholamines (TOT. UR. CAT.) in a large population of out-patients suffering from essential arterial hypertension (EAH). A total of 986 patients were examined (540 women and 426 men aged between 15 and 87 years) suffering form slight or moderate EAH (WHO stage 1-2). After a wash-out period of two weeks, systolic and diastolic arterial pressure was measured together with heart rate in clino- and orthostatism. Blood samples were collected to determine PRA and plasma aldosterone, and lastly a 24-hour urine collection was made to measure the total quantity of catecholamines. It emerged that there was a significant increase in systolic pressure, whereas heart rate and PRA diminished significantly when correlated with age; diastolic pressure was also considerably lower, but did not reach statistical significance. Moreover, it was found that there was a significant positive correlation between PRA and TOT. UR. CAT., whereas no correlation was found between age and plasma aldosterone and between blood pressure and the various endocrine parameters examined. These data confirm the changes in the biological, hemodynamic and endocrine profiles observed in elderly hypertensive patients in comparison to young hypertensive patients, and suggests that age may be an important predictive factor of the activity of both the renin-angiotensin and sympathetic nervous system which appear to be closely connected and gradually attenuated by age.

Adolescent↗
PubMed1993

Total body, spine, and femur dual X-ray absorptiometry in spinal osteoporosis.

The aim of this study was to evaluate the ability of dual x-ray absorptiometry (DXA) to discriminate between normal and osteoporotic patients. A total of 152 postmenopausal women entered the study: 73 (aged 61.2 +/- 8 years) had established postmenopausal osteoporosis with one or more vertebral crushes on lateral X-ray of spine, and 79 (aged 59.3 +/- 7.8 years) had no vertebral fractures. Measurements of bone mineral content (BMC) in grams, bone mineral density (BMD) in g/cm2 and body composition (lean and fat mass in grams) of total body, lumbar spine (L2-L4), and femur (neck, trochanter, Ward's triangle) were carried out with a LUNAR DPX densitometer. In all sites, BMD values of osteoporotic patients were significantly lower than those of the control subjects. The higher Z-score was found for total body density (-2.14) followed by L2-L4 (-2.0), femoral neck (-1.93), Ward's triangle (-1.69), and trochanter (-1.4). Only the trochanter Z-score was significantly different compared with the other sites. A fracture threshold was determined for each site from osteoporotic patients and normal controls: with a sensitivity set at 90%, the best specificity was obtained at the lumbar spine and total body sites (89% and 84%, respectively). BMD values were highly related to lean and fat body mass, but bone loss with age was unrelated to soft tissue change. In conclusion, BMD measurements at different skeletal sites enable detection of spinal osteoporosis although sensitivity for femoral areas was less with respect to total body and L2-L4 BMD values.

Absorptiometry, Photon↗
PubMed1992

Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture.

OBJECTIVE: To examine the effects of taking drugs affecting bone metabolism on the risk of hip fracture in women aged over 50 years. DESIGN: Retrospective, population based, case-control study by questionnaire. SETTING: 14 centres in six countries in southern Europe. SUBJECTS: 2086 women with hip fracture and 3532 control women matched for age. MAIN OUTCOME MEASURES: Number of drugs affecting bone metabolism taken and length taken for. RESULTS: Women taking drugs affecting bone metabolism had a significantly decreased risk of hip fracture. After adjustment for differences in other risk factors, the relative risk of hip fractures was 0.55 (95% confidence interval 0.31 to 0.85) in women taking oestrogens, 0.75 (0.60 to 0.94) in those taking calcium, and 0.69 (0.51 to 0.92) in those taking calcitonin. The fall in risk was not significant for anabolic steroids (0.6 (0.29 to 1.22)). Neither vitamin D nor fluorides were associated with a significant decrease in the risk of hip fracture. The effect on hip fracture risk increased significantly with increasing duration of exposure (risk ratio 0.8 (0.61 to 1.05) for less than median exposure v 0.66 (0.5 to 0.88) for greater than median exposure). Drugs were equally effective in older and younger women, with the exception of oestrogen. CONCLUSIONS: Oestrogen, calcium, and calcitonins significantly decrease the risk of hip fracture. Short term intervention late in the natural course of osteoporosis may have significant effects on the incidence of hip fracture.

Aged↗
PubMed1992

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss.

In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of 99mTc-methylene-dichloro-bisphosphonate (99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or placebo. Treatment with sCT significantly increased VMC by 2.7 +/- 0.9% at 6 months, and 3.3 +/- 0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6 +/- 0.5%, and -3.5 +/- 0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P less than 0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.

Administration, Intranasal↗
PubMed1992

Short-term treatment of Paget's disease of bone with ipriflavone.

Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone.

Administration, Oral↗
PubMed1992

Treatment of bone metastases with dichloromethylene bisphosphonate.

PURPOSE: The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS: Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS: Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B. CONCLUSIONS: We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.

Antineoplastic Combined Chemotherapy Protocols↗