1,721,211 research outputs found
Calcium supplementation and risk of cardiovascular disease
Full text linkWith the outcome to demonstrate the efficacy of calcium to prevent the incidence of fractures many randomized controlled trials have been performed in the past two decades, with conflicting results. A RR of 0.86 for non-vertebral fractures and a RR of 0.91 for hip fractures on eight trials were demonstrated. Calcium supplementation is considered particularly important when baseline calcium intake is low. More recently WHI CaD Study indicated hat calcium supplements with or without vitamin D represent a factor risk for cardiovascular events. On the other hand
the beneficial effect of a correct calcium intake in attaining and maintaining bone mass across the life is largely demonstrated.
There is an urgent need for more research to gain insight into the mechanisms of the adverse vascular effect of calcium. Moreover, more extensive data about the incidence of cardiovascular adverse events coming from randomized controlled intervention trials in osteoporosis, in which calcium plus Vitamin D were utilized, might be achieve
Lasofoxifene: a new-generation SERM for the treatment of postmenopausal osteoporosis
No full textLasofoxifene is a new-generation selective estrogen receptor modulator that completed the Phase III development program for the prevention and treatment of osteoporosis in postmenopausal women. This compound has a remarkably improved oral bioavailability with respect to other selective estrogen receptor modulators owing to its increased resistance to intestinal wall glucuronidation. In both preclinical and short-term Phase II clinical studies, lasofoxifene showed a favorable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. The recent results from Phase III clinical trials demonstrated the clinical efficacy of this drug in the prevention of vertebral and nonvertebral fractures. The purpose of this article is to review the clinical evidence for the use of lasofoxifene in women after menopause and to discuss how it will fit into the treatment of postmenopausal osteoporosis. © 2009, Expert Reviews Ltd. All rights reserved
Heart failure: pathophysiology and clinical picture.
No full textDespite its high prevalence and significant rates of associated morbidity and mortality, the syndrome of decompensated heart failure (HF) remains poorly defined and vastly understudied. HF is due to several mechanisms including pump dysfunction disorder, neurohormonal activation disorder, and salt-water retention disorder. The first step of the syndrome includes cardiac damage and remodeling in terms of coronary disease systo diastolic dysfunction and myocardial metabolism alterations. Neurohormonal activation and hydrosaline retention occur during successive steps in response to cardiac injury for compensatory reasons. Both mechanisms provide inotropic support to the failing heart increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure. However, they are deleterious to cardiocirculatory homeostasis in the late stage. Further factors involve structural changes, such as loss of myofilaments, apoptosis and disorganization of the cytoskeleton, as well as disturbances in Ca homeostasis, alteration in receptor density, signal transduction, and collagen synthesis. Each disorder contributes at a different time to HF development and worsening. Clinical presentation depends on pulmonary congestion, organ perfusion, presence of coronary disease, fluid retention and systemic pressure. For these reasons, the picture of HF is widely varied
Vitamin D deficiency and primary hyperparathyroidism
No full textVitamin D via its receptor has essential actions on parathyroid cells, inhibiting PTH secretion, and parathyroid cell proliferation. While the effects of vitamin D depletion in the pathogenesis of secondary hyperparathyroidism in elderly individuals or in the occurrence of parathyroid hyperplasia in patients with renal insufficiency are well established, the association between hypovitaminosis D and primary hyperparathyroidism (P-HPT) has only recently become appreciated. In different cohorts of patients with P-HPT, vitamin D deficiency has been recently associated with higher PTH levels, larger adenomas, and a more severe
phenotype (including osteitis fibrosa cystica) as well as negative post-operative outcomes following parathyroidectomy. Despite current guidelines recommend measurement of serum 25OHD (25-hydroxy-cholecalciferol) in P-HPT and their repletion if the levels are <20 ng/ml, future well-designed trials of vitamin D supplementation in P-HPT patients with coexisting vitamin D deficiency are needed to evaluate the risk/benefit profile of this treatment
Aromatase activity and bone homeostasis in men
No full textIt is known that sex steroid hormones play an important role in the maintenance of bone mass in males as well as in females. Even though androgens are the major sex steroids in men, their primacy in regulating male skeletal remodeling has been increasingly questioned as direct and indirect evidence emerged suggesting that estrogens may also play a major role in male skeletal health. Recent data suggested that a threshold level of bioavailable estradiol is needed to prevent bone loss, and that with aging an increasing percentage of elderly men begin to
fall below this level. The testes account for, at most, 15% of circulating estrogens in the male; the remaining 85% comes from peripheral aromatization of androgen precursors in different tissues, including bone. Human models of aromatase deficiency were the first to demonstrate the critical importance of the
conversion of circulating androgens into estrogen in regulating male skeletal homeostasis. All four cases of aromatase-deficient men reported to date showed an identical skeletal phenotype, characterized by tall stature due to continued longitudinal growth, unfused epiphyses, high bone turnover, and osteopenia.
Studies using knockout mice along with experimental observations in rats treated with an aromatase inhibitor provided useful information about the importance of aromatase in the male skeleton. Confirmatory evidence comes from recent
interventional studies in adult men using aromatase inhibition, which confirmed that estrogens are critically important to the male skeleton by helping to control rates of bone remodeling. Intriguingly, common polymorphisms at the human aromatase (CYP19) gene have been associated with differences in aromatase activity, bone turnover, and rates of bone loss in elderly men, suggesting that variations in aromatase efficiency may also be relevant for skeletal homeostasis. Several additional mechanisms have been proposed in which aromatase activity could be modulated under certain circumstances in different tissues. Additional studies are needed to identify how these genetic, environmental, pathological, and pharmacological influences might modulate aromatase activity in vivo,
increasing or reducing estrogen production in males and thereby affecting skeletal health
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