Is estrogen receptor alpha key to controlling bones' resistance to fracture?

The ability of bones to withstand functional loading without damage depends upon their cell populations establishing and subsequently maintaining a mass and architecture that are appropriately robust for the purpose. In women, the rapid loss of bone associated with the menopause represents a steplike decline in the effectiveness of this process with consequent increase in bone fragility. In men, loss of bone tissue and reduction in bone strength are more gradual and the increased incidence of fragility fractures occurs later. In both sexes, bone mass is associated with levels of bioavailable estrogen. This poses the major question as to how the presence or concentration of the reproductive hormone estrogen influences the relationship between bone mass and bone loading. In this paper, we briefly review evidence of the mechanism(s) by which the mechanical strains engendered by loading influence bone cells to establish and maintain structurally competent bone architecture. We highlight the finding that at least one strain-related cascade responsible for adaptive control of bone architecture is mediated through estrogen receptor (ER) alpha, the number and activity of which are regulated by estrogen. We hypothesize that a major contributor to the rapid loss of bone mass that occurs in females, and the slower age-related fall in males and females, is reduced effectiveness of ER-mediated processing of strain-related information by resident bone cells.

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Osteoporosis

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0469 ◽

2020 ◽

pp. 4696-4702

Author(s):

Nicholas C. Harvey ◽

Juliet Compston ◽

Cyrus Cooper

Keyword(s):

Hip Fracture ◽

Bone Mass ◽

Distal Radius ◽

Proximal Femur ◽

Osteoporotic Fractures ◽

Fragility Fractures ◽

Healthcare Services ◽

Bone Fragility ◽

Bone Architecture ◽

Colles Fracture

Osteoporosis is characterized by a reduction in bone mass and disruption of bone architecture, resulting in increased bone fragility and fracture risk, with fractures of the distal radius (Colles’ fracture), spine, and proximal femur being most characteristic. One in two women and one in five men over the age of 50 years will suffer an osteoporotic fracture during their remaining lifetime, with massive cost to healthcare services. Osteoporotic fractures are termed fragility fractures (defined as occurring after a fall from standing height or less). They may occur at several skeletal sites but fractures of the distal radius (Colles’ fracture), spine, and proximal femur are most characteristic. The incidence of osteoporotic fractures increases markedly with age; in women, the median age for Colles’ fractures is 65 years and for hip fracture, 80 years.

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Syndecan-3 enhances anabolic bone formation through WNT signalling

10.1101/846972 ◽

2019 ◽

Author(s):

Francesca Manuela Johnson de Sousa Brito ◽

Andrew Butcher ◽

Addolorata Pisconti ◽

Blandine Poulet ◽

Amanda Prior ◽

...

Keyword(s):

Bone Formation ◽

Bone Structure ◽

Fragility Fractures ◽

Bone Fragility ◽

Wnt Signalling ◽

Bone Architecture ◽

Age Related ◽

Metabolic Bone Disorder ◽

Metabolic Bone ◽

Canonical Wnt

ABSTRACTOsteoporosis is the most common age-related metabolic bone disorder, which is characterised by low bone mass and deterioration in bone architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts to form new bone and restore bone structure, however anabolic therapeutics are few and their use is time-restricted. Here we report that Syndecan-3 (SDC3) increases new bone formation through enhancement of WNT signalling. Young adult Sdc3−/− mice have a low bone volume phenotype associated with reduced bone formation, increased bone marrow adipose tissue (BMAT), increased bone fragility and a blunted anabolic bone formation response to mechanical loading. The premature osteoporosis-like phenotype of Sdc3−/− mice is primarily explained by delayed osteoblast maturation and impaired osteoblast function, with contributing increased osteoclast-mediated bone resorption. Mechanistically, SDC3 enhances canonical WNT signalling in osteoblasts through stabilisation of Frizzled 1, making SDC3 an attractive target for novel anabolic drug development.

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Mice lacking estrogen receptor [alpha] in hypothalamic POMC neurons display enhanced estrogenic response on cortical bone mass

Bone Abstracts ◽

10.1530/boneabs.5.ht2 ◽

2016 ◽

Author(s):

Helen Farman ◽

Sara Windahl ◽

Deborah Clegg ◽

Shang Kui Xie ◽

Lars Westberg ◽

...

Keyword(s):

Estrogen Receptor ◽

Bone Mass ◽

Cortical Bone ◽

Estrogen Receptor Alpha ◽

Receptor Alpha ◽

Cortical Bone Mass

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Aging and the Osteogenic Response to Mechanical Loading

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.11.s1.s137 ◽

2001 ◽

Vol 11 (s1) ◽

pp. S137-S142 ◽

Cited By ~ 26

Author(s):

Wendy M. Kohrt

Keyword(s):

Growth Factors ◽

Bone Mass ◽

Mechanical Loading ◽

Bone Cells ◽

Weight Bearing ◽

Bone Modeling ◽

Mineral Density ◽

Increase Bone Mass ◽

Age Related ◽

Osteogenic Response

The osteogenic response to mechanical stress is blunted with aging. It has been postulated that this decline in responsiveness is related to (a) a limited ability to engender the strain necessary to reach the bone modeling threshold, due to decreased muscle mass and strength, and/or (b) a decline in certain hormones or growth factors that may interact with mechanical signals to change the sensitivity of bone cells to strain. There is reason to believe that both of these factors contribute to the reduced ability to increase bone mass through exercise with advancing age. Weight-bearing endurance exercise and resistance exercise have both been found to increase bone mass in older women and men. However, exercise training studies involving older individuals have generally resulted in increased bone mineral density only when the exercise is quite vigorous. There is also evidence that the osteogenic response to mechanical loading is enhanced by estrogens. Whether age-related changes in other factors (e.g., other hormones, growth factors, cytokines) also contribute to the reduced responsiveness of the aged skeleton to mechanical loading remains to be investigated.

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The Role of microRNAs in Osteoporosis Diagnostics

Osteologie/Osteology ◽

10.1055/a-1514-1800 ◽

2021 ◽

Vol 30 (03) ◽

pp. 222-229

Author(s):

Matthias Hackl ◽

Elisabeth Semmelrock ◽

Johannes Grillari

Keyword(s):

Bone Mass ◽

Bone Metabolism ◽

Messenger Rna ◽

Biological Fluids ◽

Clinical Diagnostics ◽

Bone Architecture ◽

Estrogen Metabolism ◽

Age Related

AbstractMicroRNAs (miRNAs) are short (18–24 nucleotides) non-coding RNA sequences that regulate gene expression via binding of messenger RNA. It is estimated that miRNAs co-regulate the expression of more than 70% of all human genes, many of which fulfil important roles in bone metabolism and muscle function. In-vitro and in-vivo experiments have shown that the targeted loss of miRNAs in distinct bone cell types (osteoblasts and osteoclasts) results in altered bone mass and bone architecture. These results emphasize the biological relevance of miRNAs for bone health.MiRNAs are not only considered as novel bone biomarkers because of their biological importance to bone metabolism, but also on the basis of other favorable properties: 1) Secretion of miRNAs from cells enables “minimally invasive” detection in biological fluids such as serum. 2) High stability of miRNAs in serum enables the retrospective analysis of frozen blood specimens. 3) Quantification of miRNAs in the serum is based on the RT-PCR - a robust method that is considered as the gold standard for the analysis of nucleic acids in clinical diagnostics.With regard to osteoporosis, it has been shown that many of the known risk factors are characterized by distinct miRNA profiles in the affected tissues: i) age-related loss of bone mass, ii) sarcopenia, iii) changes in estrogen metabolism and related changes Loss of bone mass, and iv) diabetes. Therefore, numerous studies in recent years have dealt with the characterization of miRNAs in the serum of osteoporosis patients and healthy controls, and were able to identify recurring miRNA patterns that are characteristic of osteoporosis. These novel biomarkers have great potential for the diagnosis and prognosis of osteoporosis and its clinical outcomes.The aim of this article is to give a summary of the current state of knowledge on the research and application of miRNA biomarkers in osteoporosis.

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Association of vitamin D and osteocalcin levels in post-menopausal women with osteoporosis

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20170936 ◽

2017 ◽

Vol 6 (4) ◽

pp. 1244

Author(s):

Yogiraj Vaijanathrao Chidre ◽

Amir Babansab Shaikh

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Vitamin D Deficiency ◽

Fragility Fractures ◽

Bone Fragility ◽

Vitamin D Supplementation ◽

Mineral Density ◽

Age Related ◽

Calcium Phosphorus ◽

Post Menopausal

Background: Osteoporosis is a common age related problem especially in women, with a consequent increase in bone fragility and susceptibility to fracture. Apart from Calcium, another nutrient that plays an important role in the mineralization of skeleton in Vitamin D. Osteocalcin, which is produced primarily by osteoblasts during bone formation, is considered to be one of the markers for osteoporosis.Methods: 314 women above the age of 40 were included into the study. A thorough physical and clinical examination, assessment of vital parameters, anthropometry evaluation was done for all patients. Bone mineral density was calculated using central DXA osteodensitometer at lumbar spine L1-L4, hip and ultradistal radius (in some cases.). Blood samples were taken for the detection of ionized calcium, phosphorus, alkaline phosphatase, 25hydroxivitamin D (25 ODH) and serum parathyroid hormone (PTH) by chemiluminiscent assay. Bone markers such as osteocalcin were measured as required.Results: Out of the 314 women attending our OPD, 96 of them were diagnosed as having osteoporosis. 24 out of them had fragility fractures, mainly of the hip, and 82 had ostepenia. Elevated levels of calcium (8.96 mg/dl), parathyroid hormone (58.76 pg/ml) and osteocalcin (24.46 ng/ml) were observed. Vitamin D deficiency of ≤ 20 was seen in 59 (63%) of the cases, insufficient in 23 (24%) and only 12 (13%) of these women had normal Vitamin D levels.Conclusions: Osteocalcin is a promising marker for the detection of osteoporosis. There is a considerable Vitamin D deficiency among the women with osteoporosis, and it is under-treated. It is essential to provide Vitamin D supplementation to these women especially those who are at high risk for fragility fractures.

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Female Mice Lacking Estrogen Receptor-Alpha in Osteoblasts Have Compromised Bone Mass and Strength

Journal of Bone and Mineral Research ◽

10.1002/jbmr.2082 ◽

2014 ◽

Vol 29 (2) ◽

pp. 370-379 ◽

Cited By ~ 62

Author(s):

Katherine M Melville ◽

Natalie H Kelly ◽

Sohaib A Khan ◽

John C Schimenti ◽

F Patrick Ross ◽

...

Keyword(s):

Estrogen Receptor ◽

Bone Mass ◽

Estrogen Receptor Alpha ◽

Receptor Alpha ◽

Female Mice

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Nutritional aspects of the prevention and treatment of osteoporosis

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302010000200014 ◽

2010 ◽

Vol 54 (2) ◽

pp. 179-185 ◽

Cited By ~ 29

Author(s):

Bárbara Santarosa Emo Peters ◽

Lígia Araújo Martini

Keyword(s):

Bone Mass ◽

Bone Health ◽

Critical Role ◽

Bone Fragility ◽

Vitamin Supplementation ◽

Treatment Of Osteoporosis ◽

Age Related ◽

Consequent Increase ◽

Global Health Problem ◽

Optimal Protection

Osteoporosis is a global health problem characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Nutrition plays a critical role in reducing the risk of osteoporosis through its effect on all of these fragility factors, especially on the development and maintenance of bone mass. An adequate calcium, vitamin D and protein intake resulted in reduced bone remodeling, better calcium retention, reduced age-related bone loss, and reduced fracture risk. Recent evidence indicates that a healthy dietary pattern including dairy products (mainly fat free), fruit and vegetables and adequate amounts of meat, fish and poultry is positively related to bone health. Furthermore, mineral and vitamin supplementation should be closely monitored by health professionals since it could have adverse effects and be insufficient to ensure optimal protection of bone health.

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