The role of estrogens for male bone health

Ohlsson, Claes; Vandenput, Liesbeth

doi:10.1530/eje-09-0118

Cited by 52 publications

(49 citation statements)

References 63 publications

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“…In men, however, the relative contribution of androgens versus estrogens in the regulation of bone metabolism remains uncertain. Animal studies demonstrate that both E2, via activation of ERα, and testosterone, via activation of the androgen receptor, regulate bone mass in male rodents (30). The present finding of a substantially reduced trabecular bone volume in male Dmp1-ERα −/− mice supports previous studies suggesting that estrogen action via ERα is indeed crucial for male bone health.…”

Section: Discussionsupporting

confidence: 89%

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.

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122

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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: Discussionsupporting

confidence: 89%

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.

Self Cite

122

113

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“…of E2 (4-90 μg/d) in boys have been shown to stimulate ulnar growth (60) and play an essential role in bone development in both genders during the pubertal growth spurt (61)(62)(63). Due to the low dosing of E2 used in this study coupled with its local, slow release using the ND/G vehicle, our therapeutic approach may represent a clinical application with superior safety and efficacy.…”

Section: Discussionmentioning

confidence: 99%

Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen–nanodiamond hydrogel

Hong

Song

Lee

et al. 2017

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

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Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17β-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2's clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-crosslinkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.nanomedicine | cleft palate | craniofacial medicine | nanodiamond | drug delivery

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“…A previous publication reported that low E2 levels could predict increased fractures risk independent of testosterone; on the contrary, men with low testosterone but normal E2 levels did not show an increased fractures risk. In multivariate analysis, free E2 was an independent fracture predictor in those elderly men (12).…”

Section: Discussionmentioning

confidence: 91%

“…Serum E2 was also shown to correlate better than testosterone in relation to BMD and its decrease in aging men (12). Different authors (12,23) reported that bone loss exceeded formation when E2 levels were 31 pg/mL or below in aging men.…”

Section: Discussionmentioning

confidence: 98%

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Total estradiol, rather than testosterone levels, predicts osteoporosis in aging men

Clapauch¹,

Mattos²,

Silva³

et al. 2009

Arq Bras Endocrinol Metab

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Objective: To study and establish sex hormone cutoff levels for osteoporosis risk in men over 50 years old. Methods: Case-control study of 216 men > 50 years, 110 with osteoporosis (O) and 106 with normal bone density (C). We measured estradiol (E2), sex hormone binding globulin (SHBG), total testosterone (TT) and albumin. Free testosterone (FT) and bioavailable testosterone (BT) were calculated through Vermeulen's formula. Results: There was no difference in TT between groups. Relative risks of osteoporosis were 1.89 for E2 < 37 pg/mL (p = 0.02); 1.91 for SHBG > 55 nmol/L (p = 0.019); 2.5 for FT < 7 ng/dL (p = 0.015); 2.7 for BT < 180 ng/dL (p = 0.0003). Conclusions:In men over 50 years old, TT was not indicative of osteoporosis risk while E2 < 37 ng/mL was. SHBG > 55 nmol/L, FT < 7 ng/dL and BT < 180 ng/dL can represent additional indications for osteoporosis screening in men over 50 years old. Arq Bras Endocrinol Metab. 2009;53(8):1020-5 Keywords Male osteoporosis; estradiol; testosterone; free estradiol; free testosterone; SHBG resumo Objetivo: Estudar e estabelecer pontos de corte dos hormônios sexuais para risco de osteoporose em homens após os 50 anos de idade. Métodos: Estudo caso-controle de 216 homens > 50 anos, 110 com osteoporose e 106 com densidade óssea normal. Foram dosados: estradiol (E2), globulina ligadora de hormônios sexuais (SHBG), testosterona total (TT) e albumina. Foram calculadas: testosterona livre (TLC) e testosterona biodisponível (TB) pela fórmula de Vermeulen. Resultados: Não houve diferença na TT entre os grupos. Os riscos relativos de osteoporose foram de 1,89 para E2 < 37 pg/mL (p = 0,02); 1,91 para SHBG > 55 nmol/L (p = 0,019); 2,5 para TLC < 7 ng/dL (p = 0,015) e 2,7 para TB < 180 ng/dL (p = 0,0003). Conclusões: Em homens acima de 50 anos, TT não indicou risco de osteoporose, mas E2 < 37 pg/mL sim. SHBG > 55 nmol/L, TLC < 7 ng/dL e TB < 180 ng/dL podem representar indicações adicionais para pesquisa de osteoporose em homens acima de 50 anos. Arq Bras Endocrinol Metab. 2009;53(8):1020-5 Descritores

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The role of estrogens for male bone health

Cited by 52 publications

References 63 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

Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen–nanodiamond hydrogel

Total estradiol, rather than testosterone levels, predicts osteoporosis in aging men

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