Selective Estrogen Receptor Modulator Inhibits Osteocyte Apoptosis during Abrupt Estrogen Withdrawal: Implications for Bone Quality Maintenance

Huber, C.; Collishaw, Stephan; Mosley, John R.; Reeve, J.; Noble, Brendon

doi:10.1007/s00223-007-9049-6

Cited by 33 publications

(22 citation statements)

References 22 publications

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“…Sclerostin is expressed by osteocytes [1]. Estrogens are potent survival factors for osteocytes, as estrogen deprivation significantly increases osteocyte death [20,21]. Estrogen also prevents sclerostin upregulation in osteocytic cells [11].…”

Section: Discussionmentioning

confidence: 99%

Effects of Sex Steroids on Serum Sclerostin Levels during the Menstrual Cycle

Çidem

Usta²,

Karacan

et al. 2013

Gynecol Obstet Invest

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Background/Aims: Previous studies on the effects of estrogen on sclerostin regulation were conducted in postmenopausal women in humans or animals following estrogen treatment or induced estrogen deficiency. The aim of this study was to evaluate the effects of sex hormones on serum sclerostin levels in premenopausal women with normal menstrual cycles. Methods: A prospective observational clinical study. 80 voluntary premenopausal women were recruited for the study. Data from 31 patients were available for the statistical analysis. Serum sclerostin, free estradiol, free testosterone, and progesterone levels were measured during the menstruation, late follicular and mid-luteal phases. The unique protocol IDs were BEAH FTR-4 and NCT01418924 at ClinicalTrials.gov ID. Results: Serum sclerostin values were 1.03 ± 0.58 ng/ml during the menstruation phase, 1.0 ± 0.36 ng/ml during the late follicular phase, and 1.18 ± 0.67 ng/ml during the mid-luteal phase (p = 0.543). There was no significant relationship between serum levels of sex steroids and sclerostin. Conclusions: Previous studies have not investigated the impact of sex hormone fluctuations on serum sclerostin levels during the menstrual cycle. The present study shows that serum sclerostin levels were not affected by sex steroids in premenopausal women with normal menstrual cycles.

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Section: Discussionmentioning

confidence: 99%

Effects of Sex Steroids on Serum Sclerostin Levels during the Menstrual Cycle

Çidem

Usta²,

Karacan

et al. 2013

Gynecol Obstet Invest

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“…Osteocytes have a key role in the detection and repair of microcrack damage in bone [34][35][36]. Estrogen withdrawal leads to accelerated osteocyte apoptosis in women and in rats [37,38], while E 2 and selective estrogen receptor modulators (SERMs) have been shown to inhibit this reduction in osteocyte viability [39,40]. Two studies that compared bone samples in women with or without osteoporotic vertebral fractures found a significantly lower osteocyte density in women with fracture [41,42].…”

Section: Discussionmentioning

confidence: 97%

Endogenous Estradiol and The Risk of Incident Fracture in Postmenopausal Women: The OPUS Study

et al. 2012

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Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study. Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for all subjects at baseline and 6-year follow-up. Nonfasting blood samples were taken at baseline for E(2), SHBG, DHEAS, and bone turnover markers. Incident nonvertebral fractures were self-reported and verified; vertebral fractures were diagnosed at a single center from spinal radiographs. Medical and lifestyle data were obtained by questionnaire at each visit. Thirty-nine subjects had an incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the lowest quartile predicted vertebral fracture independent of confounders including age, body mass index, bone mineral density, bone turnover, fracture history, and use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI] 1.52-5.82) by logistic regression. A calculated free estradiol index was not a stronger predictor than total E(2). Higher SHBG predicted vertebral fracture independently of age and body mass index, but not independently of E(2), bone mineral density, or prevalent fracture. Low DHEAS did not predict vertebral fracture. Nonvertebral fractures were not predicted by any of E(2), SHBG, or DHEAS, either in univariate or multivariate analyses. These findings suggest that there may be mechanistic differences in the protective effect of E(2) at vertebral compared with nonvertebral sites.

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“…DAPI emits blue fluorescence upon binding to DNA and thus the regions of DAPI-negative stain observed in this study signify areas where the cells have already died and the DNA has degraded. Future studies incorporating a triple staining technique with both lactate dehydrogenase staining of viable cells in combination with propidium iodide staining of necrotic cells [32,33], together with caspase-3 staining of apoptotic cells (demonstrated in this study) would elucidate the mechanism of cell death. Nonetheless, in this study the DAPI-negative area was seen to increase with the severity of temperature elevation.…”

Section: Discussionmentioning

confidence: 98%

Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression in vivo

Duffy

Tallon

Cheung

et al. 2016

J. R. Soc. Interface.

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Bone is often subject to harsh temperatures during orthopaedic procedures resulting in thermally induced bone damage, which may affect the healing response. Postsurgical healing of bone is essential to the success of surgery, therefore, an understanding of the thermally induced responses of bone cells to clinically relevant temperatures in vivo is required. Osteocytes have been shown to be integrally involved in the bone remodelling cascade, via apoptosis, in micro-damage systems. However, it is unknown whether this relationship is similar following thermal damage. Sprague-Dawley rat tibia were exposed to clinically relevant temperatures (478C or 608C) to investigate the role of osteocytes in modulating remodelling related factors. Immunohistochemistry was used to quantify osteocyte thermal damage (activated caspase-3). Thermally induced pro-osteoclastogenic genes (Rankl, Opg and M-csf ), in addition to genes known to mediate osteoblast and osteoclast differentiation via prostaglandin production (Cox2), vascularization (Vegf ) and inflammatory (Il1a) responses, were investigated using gene expression analysis. The results demonstrate that heat-treatment induced significant bone tissue and cellular damage. Pro-osteoclastogenic genes were upregulated depending on the amount of temperature elevation compared with the control. Taken together, the results of this study demonstrate the in vivo effect of thermally induced osteocyte damage on the gene expression profile.

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Selective Estrogen Receptor Modulator Inhibits Osteocyte Apoptosis during Abrupt Estrogen Withdrawal: Implications for Bone Quality Maintenance

Cited by 33 publications

References 22 publications

Effects of Sex Steroids on Serum Sclerostin Levels during the Menstrual Cycle

Effects of Sex Steroids on Serum Sclerostin Levels during the Menstrual Cycle

Endogenous Estradiol and The Risk of Incident Fracture in Postmenopausal Women: The OPUS Study

Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression in vivo

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