Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications

Noirrit‐Esclassan, Emmanuelle; Valera, Marie-Cécile; Trémollières, Florence; Arnal, Jean‐François; Lenfant, Françoise; Fontaine, Coralie; Vinel, Alexia

doi:10.3390/ijms22041568

Cited by 95 publications

(30 citation statements)

References 142 publications

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“…Furthermore, adding a daily injection of goserelin prevented production of FSH, thus creating models suitable for studying menopause-specific concentrations of oestradiol. In our models, reducing oestradiol to peri- or post-menopausal concentrations significantly reduced bone volume through increased osteoclast activity, as is also observed in women during the same representative stages of menopause, providing evidence that our model is representative of the human condition ( 32 , 33 ). Zol has well-characterised properties of inhibiting bone resorption via preventing osteoclast activity and causing osteoclast apoptosis in both mouse models and humans ( 34 – 36 ).…”

Section: Discussionsupporting

confidence: 77%

Oestradiol Contributes to Differential Antitumour Effects of Adjuvant Zoledronic Acid Observed Between Pre- and Post-Menopausal Women

et al. 2021

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Clinical trials have demonstrated that adding zoledronic acid (Zol) to (neo)adjuvant standard of care has differential antitumour effects in pre- and post-menopausal women: Both benefit from reduced recurrence in bone; however, while postmenopausal women also incur survival benefit, none is seen in premenopausal women treated with adjuvant bisphosphonates. In the current study, we have used mouse models to investigate the role of oestradiol in modulating potential antitumour effects of Zol. Pre-, peri-, and post-menopausal concentrations of oestradiol were modelled in BALB/c wild-type, BALB/c nude, and C57BL/6 mice by ovariectomy followed by supplementation with oestradiol. Mice also received 40 mg/kg/day goserelin to prevent ovariectomy-induced increases in follicle-stimulating hormone (FSH). Metastasis was modelled following injection of MDA-MB-231, 4T1, or E0771 cells after ovariectomy and saline or 100 μg/kg Zol administered weekly. Supplementing ovariectomised mice with 12.5 mg/ml, 1.38 mg/ml, and 0 ng/ml oestradiol, in the presence of goserelin, resulted in serum concentrations of 153.16 ± 18.10 pg/ml, 48.64 ± 18.44 pg/ml, and 1.00 ± 0.27 pg/ml oestradiol, which are equivalent to concentrations found in pre-, peri-, and post-menopausal humans. Osteoclast activity was increased 1.5–1.8-fold with peri- and post-menopausal compared with premenopausal oestradiol, resulting in a 1.34–1.69-fold reduction in trabecular bone. Zol increased trabecular bone in all groups but did not restore bone to volumes observed under premenopausal conditions. In tumour-bearing mice, Zol reduced bone metastases in BALB/c (wild-type and nude), with greatest effects seen under pre- and post-menopausal concentrations of oestradiol. Zol did not affect soft tissue metastases in immunocompetent BALB/c mice but increased metastases 3.95-fold in C57BL/6 mice under premenopausal concentrations of oestradiol. In contrast, Zol significantly reduced soft tissue metastases 2.07 and 4.69-fold in immunocompetent BALB/c and C57BL/6 mice under postmenopausal oestradiol, mirroring the results of the clinical trials of (neo)adjuvant bisphosphonates. No effects on soft tissue metastases were observed in immunocompromised mice, and differences in antitumour response did not correlate with musculoaponeurotic fibrosarcoma (MAF), macrophage capping protein (CAPG), or PDZ domain containing protein GIPC1 (GIPC1) expression. In conclusion, oestradiol contributes to altered antitumour effects of Zol observed between pre- and post-menopausal women. However, other immunological/microenvironmental factors are also likely to contribute to this phenomenon.

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Section: Discussionsupporting

confidence: 77%

Oestradiol Contributes to Differential Antitumour Effects of Adjuvant Zoledronic Acid Observed Between Pre- and Post-Menopausal Women

et al. 2021

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“…In postmenopausal middle-aged and elderly women, because of aging and decreased sex hormone secretion, bone resorption is greater than its formation, resulting in an increased risk for osteoporosis and fracture [ 20 ]. By contrast, bone loss in men is more due to a reduction of osteogenesis, which leads to the thinning of the trabeculae [ 21 ]. The cortical bone area of males continues to increase to 60–70 years old, while the periosteum of females begins to expand from 50 years old.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Lumbar Bone Density in Middle-Aged and Elderly Subjects: A Correlation Study between T-Scores Determined by the DEXA Scan and Hounsfield Units from CT

Zhang

Luo

et al. 2021

Journal of Healthcare Engineering

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Purpose. To describe the characteristics of lumbar bone density in middle-aged and elderly subjects and explore whether there is a correlation between computed tomography (CT) values and the bone mineral density (BMD) T-scores of the lumbar vertebral cancellous bone. Methods. Forty-two subjects, including 25 males and 17 females, with a mean age of 56 years, who underwent BMD measurement and lumbar multislice spiral CT scan at the China Rehabilitation Research Center from January 2019 to December 2019 were selected. Dual-energy X-ray absorptiometry (DEXA) was applied to obtain the total BMD T-scores of the lumbar L1–L4 vertebrae. Results. The CT values decreased from L1 to L4 and were 145.91 ± 8.686 HU, 143.18 ± 8.598 HU, 137.39 ± 8.276 HU, and 135.23 ± 8.219 HU, respectively. The total CT value of L1–L4 was 140.43 ± 4.199 HU. The mean total BMD T-score of L1–L4 was −0.94. The CT values of the L1–L4 vertebrae were positively correlated with the total BMD T-scores of L1–L4 (r = 0.349, P < 0.001 ). The CT value of the left third of the same vertebrae was the highest, and there was a strong positive correlation between the regional CT value of the lumbar spine and the entire vertebra CT values (r > 0.7). Conclusion. The CT values of the lumbar spine can assist the measurement of the T-scores of lumbar BMD, which could aid in early opportunistic screening for osteopenia and preventing osteoporosis and vertebral compression fractures in middle-aged and elderly subjects. This trial is registered with ChiCTR2100049571.

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“…Estrogen is a sex steroid hormone involved in the female reproduction of gnathostomes. It is also associated with bone metabolism and participates in osteoblastic differentiation in mammals (Komm et al, 1988;Eriksen et al, 1988;Okazaki et al, 2002;Noirrit-Esclassan et al, 2021). Therefore, the relationship between estrogen and blood calcium homeostasis has been investigated in teleosts.…”

Section: Estrogen Directly Acts On the Ubg And Promotes Ct Secretionmentioning

confidence: 99%

Influence of estrogen and the endocrine disruptor on the calcitonin functions in teleosts

Sekiguchi¹,

K²,

Suzuki³

2021

IJBEI

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In this review, we discuss the function of calcitonin (CT) during teleost reproduction and the influence of estrogen and bisphenol-A (BPA) on CT functions. CT acts as a hypocalcemic hormone in mammals. However, the hypocalcemic effect of CT remains unclear in teleosts. The effect of CT on the plasma calcium level varies among fish species and experimental conditions. On the other hand, CT has significant functions in ter ms of teleost reproduction. Plasma CT levels in some teleosts are higher in females than in males. Additionally, a correlation between plasma CT concentration and the gonadal somatic index is observed in female teleosts. In the reproductive period, estrogen (17ß-estradiol), a sex steroid, induces the synthesis of vitellogenin in the liver and promotes calcium resorption from the scales by activating osteoclasts. Vitellogenin possesses a calciumbinding property and is incorporated into oocytes through the vitellogenin receptor. The estrogen receptor is present in the ultimobranchial gland (UBG), which is the source of CT in non-mammals. The estrogen receptor is expressed in the UBG, and specific estrogen binding is detected in the UBG. In addition, estrogen induces CT secretion from the UBG. Furthermore, using the scale in vitro assay system, we found that osteoclastic activity accelerated by the estrogen was suppressed by CT. These findings imply that CT protects the scales from excess degradation of calcium at the time of teleost vitellogenesis. Additionally, we introduce the function of an endocrine disruptor such as BPA in calcium metabolism. The actions of BPA in calcium homeostasis are different from those of 17ß-estradiol. BPA suppressed both osteoclastic and osteoblastic activities and decreased both the plasma CT and calcium levels. Collectively, these issues lead to the conclusion that CT has significant function(s) during specific stages, such as reproduction, and that BPA acts differently from estrogen and disrupts the CT functions.

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Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications

Cited by 95 publications

References 142 publications

Oestradiol Contributes to Differential Antitumour Effects of Adjuvant Zoledronic Acid Observed Between Pre- and Post-Menopausal Women

Oestradiol Contributes to Differential Antitumour Effects of Adjuvant Zoledronic Acid Observed Between Pre- and Post-Menopausal Women

Characteristics of Lumbar Bone Density in Middle-Aged and Elderly Subjects: A Correlation Study between T-Scores Determined by the DEXA Scan and Hounsfield Units from CT

Influence of estrogen and the endocrine disruptor on the calcitonin functions in teleosts

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