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Estrogen Depletion (estrogen + depletion)
Selected AbstractsPerimenopausal Bone Loss: More than Estrogen DepletionJOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2001Jerilynn C. Prior No abstract is available for this article. [source] Modulation of A, peptides by estrogen in mouse modelsJOURNAL OF NEUROCHEMISTRY, Issue 1 2002H. Zheng Abstract Clinical studies have shown that estrogen deprivation through menopause is a risk factor in both the initiation and progression of Alzheimer's disease (AD) and that estrogen replacement therapy may be protective. One of the major pathological features in the human AD brain is the senile plaque, a proteinaceous structure composed mainly of heterogeneous peptides collectively known as A-beta (A,). In vitro studies have linked estrogen with A, modulation, suggesting that one-way that estrogen depletion at menopause may exacerbate the features of AD is through A, accumulation. To test this, two studies were performed on transgenic models of amyloidosis. Firstly, transgenic mice without detectable amyloid aggregates were subjected to ovariectomy and estradiol supplementation, and A, levels were assessed. Secondly, the effects of estrogen modulation were assessed in mice at an age when plaques would be forming initially. Overall, A, levels were higher in estrogen-deprived mice than intact mice, and this effect could be reversed through the administration of estradiol. These data suggest that, in vivo, estrogen depletion leads to the accumulation of A, in the CNS, which can be reversed through replacement of estradiol. These results provide evidence that post-menopausal estrogen depletion may be linked to an increased risk of AD through A, modulation. [source] Long-term ovariectomy decreases ovine compact bone viscoelasticityJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2005C. M. Les Abstract Changes in bone mineral density associated with estrogen depletion in humans do not account for all of the associated change in fracture risk, and it is possible that some of this variation may lie in changes of other aspects of bone quality. The purpose of this study was to investigate changes in viscoelastic behavior of compact bone that may be associated with estrogen depletion. Changes in compact bone viscoelastic properties associated with three years of ovariectomy were investigated with dynamic mechanical analysis (low-amplitude 3-point bending at frequencies of 1,20 Hz) using beams milled from the diaphysis of the ovine radius. The viscoelastic storage modulus was significantly (5.2%) lower at the higher frequencies for the ovariectomized animals. The general anatomic variation in storage modulus, in which cranial sectors had higher values than caudal sectors, did not change with ovariectomy. The loss tangent (tan ,, a measure of damping) was also greatly decreased (up to 83%) at high frequencies in the ovariectomized animals. Anatomic variation in tan , at low (6,12 Hz) frequencies (cranial and caudal sectors having higher values than lateral or medial sectors) was enhanced with ovariectomy. Changes in viscoelastic properties associated with long term estrogen depletion could be responsible for a significant reduction in the toughness or strength of a bone without concomitant changes in screening modalities used to evaluate bone quality (e.g., DXA, QCT, QUA). © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Skeletal health: primate model of postmenopausal osteoporosisAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009S.Y. Smith Abstract Currently, the nonhuman primate is the most widely used large animal model to evaluate the safety and efficacy of new drug entities to treat or prevent estrogen-deficiency-induced bone loss and osteoporosis. Surgical ovariectomy (OVX) induces a state of high bone turnover and rapid bone loss establishing a new steady-state bone mass within 8,9 months. Many systems in the monkey are similar to humans, including skeletal and reproductive physiology and the immune system, making this a plausible model suitable to evaluate the effects of new bone drugs. The long-term sequelae following OVX and withdrawal of monthly exposure to cyclic reproductive hormones in older female monkeys (cynomolgus and rhesus) mimics estrogen depletion and postmenopausal bone loss occurring in women. Characterization of the primate model revealed an apparent limitation to the extent of bone loss. Animals lose bone mass after OVX, but the extent of the bone loss cannot be described as osteoporotic. The small differences between OVX and sham-operated controls in many important bone measurements is overcome by including 15,20 animals per group to provide adequate statistical power. The long-term, at least 16 month, bone safety studies performed to satisfy regulatory guidelines provide an opportunity to study treatment effects for an extended period not covered in shorter-term safety studies. In vivo end-points such as densitometry and biochemical markers translate easily to clinical use, while biomechanical end-points that cannot be measured clinically can be used to predict fracture prevention. To date, the monkey OVX model has been used to support submissions for many new drugs including anabolics, bisphosphonates and selective estrogen receptor modulators. Despite its limitations, the OVX monkey model remains the best characterized of the large animal models of osteopenia and has become integral to osteoporosis drug development. Am. J. Primatol. 71:752,765, 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||