A. Trifiletti

Neridronate Prevents Bone Loss in Patients Receiving Androgen Deprivation Therapy for Prostate Cancer

Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation.

Bisphosphonates in the treatment of thalassemia-associated osteoporosis.

Thalassemia major is a common cause of skeletal morbidity, as shown by the increased fracture risk in thalassemic patients. The etiology of this bone disease is multifactorial and culminates in a state of increased bone turnover with excessive bone resorption and remodeling. Despite hormonal replacement therapy, calcium and vitamin D administration, effective iron chelation, and normalization of hemoglobin levels, patients with thalassemia major continue to lose bone mass. The increased bone turnover rate observed in thalassemic patients justifies the use of powerful anti-resorption drugs, such as bisphosphonates. To date, alendronate, pamidronate, and zoledronate seem to be effective in increasing bone mineral density and normalizing bone turnover, but more trials are necessary to evaluate their efficacy in reducing fracture risks in larger thalassemic populations.

Hepatic osteodystrophy: Does the osteoprotegerin/receptor activator of nuclear factor-kB ligand systemplay a role?

Multiple factors can contribute to the development of osteodystrophy in patients with chronic liver disease (CLD). Recently, two new cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor-kB ligand (RANKL), have been implicated in the pathogenesis of post-menopausal osteoporosis and other metabolic bone diseases. Therefore, the aim of our study was to evaluate bone metabolism, bone mineral density (BMD) and OPG/RANKL system in 65 male patients with CLD and in 65 healthy controls. Our patients showed lower BMD values than controls both at lumbar and femoral levels. Moreover, they had an unbalanced bone turnover with an increased resorption phase, as shown by high levels of urinary deoxypyridinoline and a decreased formation phase, as shown by the slightly, but significant, low levels of bone-alkaline phosphatase. Patients showed lower plasma levels of free-testosterone than controls and higher—although not significantly so—plasma levels of 17 β-estradiol. Furthermore, patients with CLD had higher levels of sex hormone-binding globulin and OPG, and lower levels of 25-hydroxyvitamin D (25-HOD)and IGF-I than the control group, while RANKL levels were similar in the two groups. In conclusion, our data do not confirm the hypothesis that the OPG/RANKL system could exert a key role in the pathogenesis of hepatic osteodystrophy, but rather that the observed increase in OPG levels may represent either the result of the inflammatory process per se or a compensation for the observed enhanced bone resorption.

Hemostatic effects of diets containing olive or soy oil in hypertensive patients

If prothrombotic mutations lead to severely altered plasma concentrations of hemostatic factors, this may have produced some early deaths and therefore an underestimation of the risk of developing myocardial infarction. Because of the extreme inclusion criteria we used, the study size has become too small to enable us to exclude reliably an effect of variants with low allele frequencies, such as FV Leiden and prothrombin 20210A mutation, that have previously been found to increase risk in young women [2,3]. Our results are therefore not inconsistent with a mild deleterious effect of these variants. Family history was a risk factor for myocardial infarction in young individuals without a cardiovascular risk factor, as a higher prevalence of familial myocardial infarction was found among cases (46.3%) compared with controls without any cardiovascular risk factor (30.9%), leading to an odds ratio of 1.9 (95% CI 0.9, 4.2). Whether this increased risk is the result of socio-economic circumstances and related lifestyle or an undiscovered genetic influence is unclear. In conclusion, in a subgroup of young survivors of myocardial infarction without any cardiovascular risk factor, we found no support for a causal role of nine prothrombotic genetic variants in the development of myocardial infarction. References

Increased Indexes of Thrombin Activation in Advanced Stages of Hypertension

Background: The hemostatic system plays an important role in thrombotic lesions, which can complicate the clinical course of hypertensive patients. The aim of this study was to verify a possible activation of the blood clotting processes, the evaluation of two markers of thrombin activation in 62 hypertensive patients, with and without vascular complications, compared with a control group. Methods and Results: In 22 patients with newly diagnosed uncomplicated essential hypertension, in 40 hypertensive patients with clinically evident vascular complications (20 patients with controlled blood pressure and 20 with uncontrolled and high blood pressure) and in 20 normotensive sex- and age-matched subjects, two indexes of thrombin generation and action, namely prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA) were evaluated. The observed values show an increase of the F1 + 2 levels in patients with overt vascular complications; those with higher blood pressure, moreover, showed FPA levels higher than those with controlled blood pressure. Conclusions: These results seem to indicate that plasma F1 + 2 levels are significantly elevated, as a marker of a thrombosis-prone status, in patients with organic damage. Successively, with progress of hypertension and increasing blood pressure, the evidence of elevated FPA levels seems to indicate a clear prethrombotic situation which could turn into a thrombotic state.

Hemostatic changes in vasculitides

The systemic vasculitides are an heterogeneous group of rare diseases characterized by inflammation and fibrinoid necrosis of blood vessel walls. Today it is well known that the inflammatory process characterizing vasculitides activates coagulation factors, inhibits anticoagulant factors, inhibits fibrinolytic processes, increases platelet activity and production and determines endothelial dysfunction. So far the mortality in vasculitides, even if falling, remains substantially high. Patients with vasculitic syndrome are at increased risk of developing atherosclerosis and in these patients prevalence of cardiovascular disease and cardiovascular events is higher than in the general population. Vasculitides can be associated with antiphospholipid syndrome. It is important to establish a strategy of antithrombotic therapy management in vasculitic patients, but this has not yet been clearly achieved.

Long-term hemostatic effects of cholesterol-lowering therapy with atorvastatin.

This study assessed hemostatic effects of an HMC-CoA reductase inhibitor, atorvastatin, on different parameters in 32 hypercholesterolemic patients of both sexes. In the patients and in 25 control subjects, plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor (PAI-1), D-dimer, prothrombin fragment 1 + 2 (F1 + 2), total cholesterol, triglycerides and fibrinogen had been measured. All these parameters were evaluated in patients after 6 and 12 months of treatment with atorvastatin at a dosage of 20 mg/day. This treatment significantly lowered the total cholesterol level in all patients. Moreover, after 6 months of atorvastatin treatment, PAI-1 and F1 + 2, which were both increased at baseline, were significantly reduced. This reduction continued after 12 months. The present results show that a reduction of hemostatic abnormalities, which exist in hypercholesterolemia, may be another important effect of the atorvastatin therapy.

Haemostatic effects of phytoestrogen genistein in postmenopausal women

INTRODUCTION Genistein is an isoflavone phytoestrogen derived from the soybean which acts as natural selective estrogen receptor modulator. Various studies have pointed out its cardioprotective role. The aim of the study was to evaluate the haemostatic effects of genistein in postmenopausal women. MATERIAL AND METHODS In this double-blind placebo-controlled trial we enrolled 104 healthy postmenopausal women with osteopenia. 53 patients (mean age 54.9+/-4.2 yr; BMI 23.4+/-3.2 Kg/m(2)) received genistein (54 mg/day) and 51 patients (mean age 55.4+/-4.3 yr; BMI 23.6+/-3.6 Kg/m(2)) received an identical placebo-tablet. Both groups received a calcium and vitamin D supplement. Plasma levels of D-dimer (DD), plasminogen activator inhibitor-1 (PAI-1) and prothrombin fragment 1+2 (F1+2) were measured at baseline and after 6 and 12 months of treatment. RESULTS Baseline characteristics of the two groups were similar. Compared with placebo, genistein decreased significantly DD (p<0.001), but did not affect PAI-1 and F 1+2 plasma levels. CONCLUSION The results of our study do not confirm effects of genistein on activation of the haemostatic system, but on the contrary the significant decrease of DD could indicate a possible cardioprotective role of genistein in postmenopausal women.

Hemostasis and Fibrinolysis Factors in First-Degree Relatives of Patients with Type 2 Diabetes without Hypertension

First-degree relatives of type 2 diabetic patients with or without a family history of hypertension are at increased risk for cardiovascular diseases. The aim of this study was to verify some possible hemostatic alterations in first-degree relatives of type 2 diabetic, normotensive and hypertensive patients. In 78 non-diabetic, normotensive first-degree relatives of type 2 diabetic patients (47 without a family history of hypertension and 31 with a family history of hypertension) and in 36 normoglycemic, normotensive subjects with no family history of hypertension, we evaluated plasma levels of fasting glucose and insulin, tissue-type plasminogen activator (t-PA), plasminogen activator-inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1 + 2 (F1+2). Insulin resistance, calculated by the HOMA model, and plasma levels of t-PA and PAI-1 were significantly higher in relatives of diabetics compared to controls. As far as the thrombin activation indexes are concerned, we detected a significant increase in DD and F1+2 in relatives of diabetics with hypertension compared to other study subjects. In conclusion, our data indicate that familial predisposition may influence the hemostatic system in first-degree relatives of diabetic and/or hypertensive patients.