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

Lanyon, Lance E.; Armstrong, Victoria; Ong, Delia; Zaman, Gul; Price, Joanna S.

doi:10.1677/joe.0.1820183

Cited by 65 publications

(39 citation statements)

References 79 publications

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“…Earlier studies have demonstrated that female but not male mice with ERα inactivation display reduced cortical osteogenic bone response to mechanical loading (19,(21)(22)(23)(24). To determine if the reduced osteogenic response to mechanical loading in female ERα −/− mice is caused by a lack of ERα in osteocytes, we loaded tibiae of female Dmp1-ERα −/− mice and WT mice using a standardized axial loading procedure.…”

Section: Resultsmentioning

confidence: 99%

“…As female mice with total ERα inactivation display reduced cortical osteogenic bone response to mechanical loading (19,(21)(22)(23)(24), and osteocytes are thought to function as the main mechanosensors in bone, it was biologically plausible to hypothesize that ERα in osteocytes is important for the osteogenic response to mechanical loading. However, the cortical osteogenic bone response to mechanical loading was normal in Dmp1-ERα −/− mice, demonstrating that ERα in osteocytes is not crucial for the osteogenic response to mechanical loading and, therefore, further studies are required to identify the ERα target cell type contributing to the osteogenic response to mechanical loading.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that female but not male mice with ERα inactivation display reduced cortical osteogenic bone response to mechanical loading (19,(21)(22)(23)(24). In addition, we recently showed that ERα is required for the cortical osteogenic response to mechanical loading in a ligand-independent manner, involving activation function-1 but not activation function-2 in ERα in female mice (20).…”

mentioning

confidence: 85%

“…It is well established that mechanical loading is a major regulator of cortical bone dimensions (19,20). Previous studies have demonstrated that female but not male mice with ERα inactivation display reduced cortical osteogenic bone response to mechanical loading (19,(21)(22)(23)(24).…”

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confidence: 99%

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Estrogen receptor-α in osteocytes is important for trabecular bone formation in male mice

Windahl

Börjesson

Farman

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

121

113

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The bone-sparing effect of estrogen in both males and females is primarily mediated via estrogen receptor-α (ERα), encoded by the Esr1 gene. ERα in osteoclasts is crucial for the trabecular bonesparing effect of estrogen in females, but it is dispensable for trabecular bone in male mice and for cortical bone in both genders. We hypothesized that ERα in osteocytes is important for trabecular bone in male mice and for cortical bone in both males and females. Dmp1-Cre mice were crossed with ERα flox/flox mice to generate mice lacking ERα protein expression specifically in osteocytes (Dmp1-ERα −/− ). Male Dmp1-ERα −/− mice displayed a substantial reduction in trabecular bone volume (−20%, P < 0.01) compared with controls. Dynamic histomorphometry revealed reduced bone formation rate (−45%, P < 0.01) but the number of osteoclasts per bone surface was unaffected in the male Dmp1-ERα −/− mice. The male Dmp1-ERα −/− mice had reduced expression of several osteoblast/osteocyte markers in bone, including Runx2, Sp7, and Dmp1 (P < 0.05). Gonadal intact Dmp1-ERα −/− female mice had no significant reduction in trabecular bone volume but ovariectomized Dmp1-ERα −/− female mice displayed an attenuated trabecular bone response to supraphysiological E2 treatment. Dmp1-ERα −/− mice of both genders had unaffected cortical bone. In conclusion, ERα in osteocytes regulates trabecular bone formation and thereby trabecular bone volume in male mice but it is dispensable for the trabecular bone in female mice and the cortical bone in both genders. We propose that the physiological trabecular bone-sparing effect of estrogen is mediated via ERα in osteocytes in males, but via ERα in osteoclasts in females.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 85%

mentioning

confidence: 99%

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Estrogen receptor-α in osteocytes is important for trabecular bone formation in male mice

Windahl

Börjesson

Farman

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

121

113

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“…The association between amenorrhea and low bone mass is well known (31). The mechanism is attributed to estrogen deficiency, which leads to an increased bone resorption, since estrogen has osteoprotective effects through specific estrogen receptor actions (32,33). Cortisol was also highly negatively correlated with spinal BMD.…”

Section: Discussionmentioning

confidence: 99%

Bone mineral density in bulimic women – influence of endocrine factors and previous anorexia

Naessén

Carlström²,

Glant³

et al. 2006

eur j endocrinol

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Objective: Data concerning bone mineral density (BMD) in bulimia nervosa are contradictory and include both low and normal values. The aim of the present study was to elucidate possible endocrineand nutrition-related factors predicting BMD in bulimic women. Design: Cross-sectional study. Methods: Seventy-seven bulimic patients and 56 age-and body mass index (BMI)-matched healthy controls were examined with respect to BMD (dual energy X-ray absorptiometry) and to serum levels of hormones and metabolic factors. Results: Bulimics had significantly lower spinal BMD and higher frequency of osteopenia in the total body than controls. Furthermore, bulimic women had significantly lower levels of estradiol-17b and free thyroxine and significantly higher cortisol levels compared with controls. Among the bulimics, 31.2% had present menstrual disturbance, 51.9% had a history of amenorrhea and 23.4% had previous anorexia nervosa. Subgroups of bulimics with a history of amenorrhea and previous anorexia nervosa had significantly lower total and spinal BMD than controls, whereas those without such history did not differ from the controls. In univariate analysis, a history of amenorrhea, cortisol, testosterone, previous anorexia nervosa, and BMI showed significant associations with spinal BMD. Multiple regression analysis including all significant variables revealed previous anorexia nervosa to be the strongest determinant of spinal BMD, accounting for 34% of the variance, while associations between endocrine factors and BMI disappeared. Conclusions: Low bone mass in bulimics may be explained by previous anorexia nervosa, whereas endocrine variables related to BMD seem to be secondary determinants that are dependent on previous anorexia nervosa and BMI.European Journal of Endocrinology 155 245-251

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Estrogen, exercise, and the skeleton

Devlin¹

2011

Evolutionary Anthropology

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Patterns of variation in bone size and shape provide crucial data for reconstructing hominin paleobiology, including ecogeographic adaptation, life history, and functional morphology. Measures of bone strength, including robusticity (diaphyseal thickness relative to length) and cross-sectional geometric properties such as moments of area, are particularly useful for inferring behavior because bone tissue adapts to its mechanical environment. Particularly during skeletal growth, exercise-induced strains can stimulate periosteal modeling so that, to some extent, bone thickness reflects individual behavior. Thus, patterns of skeletal robusticity have been used to identify gender-based activity differences, temporal shifts in mobility, and changing subsistence strategies. Although there is no doubt that mechanical loading leaves its mark on the skeleton, less is known about whether individuals differ in their skeletal responses to exercise. For example, the potential effects of hormones or growth factors on bone-strain interactions are largely unexplored. If the hormonal background can increase or decrease the effects of exercise on skeletal robusticity, then the same mechanical loads might cause different degrees of bone response in different individuals. Here I focus on the role of the hormone estrogen in modulating exercise-induced changes in human bone thickness.

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

Cited by 65 publications

References 79 publications

Estrogen receptor-α in osteocytes is important for trabecular bone formation in male mice

Estrogen receptor-α in osteocytes is important for trabecular bone formation in male mice

Bone mineral density in bulimic women – influence of endocrine factors and previous anorexia

Estrogen, exercise, and the skeleton

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