FSH Directly Regulates Bone Mass

Sun, Li; Peng, Yangyang; Sharrow, Allison C.; Iqbal, Jameel; Zhang, Zhiyuan; Papachristou, Dionysios J.; Zaidi, Samir; Zhu, Lijing; Yaroslavskiy, Beatrice B.; Zhou, Hang; Zallone, Alberta; Sairam, M.R.; Kumar, T. Rajendra; Wei, Bo; Braun, Jonathan; Cardoso-Landa, Luis; Schaffler, Mitchell B.; Moonga, Baljit S.; Blair, Harry C.; Zaidi, Mone

doi:10.1016/j.cell.2006.01.051

Cited by 643 publications

(732 citation statements)

References 51 publications

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“…A recent study suggested that FSH might directly regulate bone mass [17], but despite the changes that occur in FSH in the patients in the present study [7], there was no correlation between either BMD or markers of bone resorption or synthesis and FSH levels. This does not rule out a role for FSH, but suggests that it alone cannot be the explanation and its apparent effects on bone may reflect that it is an indirect marker of ovarian function [18].…”

Section: Discussioncontrasting

confidence: 86%

Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?

Cameron

Douglas

Brown

et al. 2010

Breast Cancer Res Treat

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mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?. Breast Cancer Research and Treatment, Springer Verlag, 2010, 123 (3) Pre-menopausal women given adjuvant chemotherapy for breast cancer experience both premature ovarian failure and loss of bone mineral density (BMD), and this study was designed to see if these observations are causally linked. MethodsChemotherapy was administered to 41 pre-menopausal women with early breast cancer enrolled prospectively in a study of ovarian function and BMD in such women given systemic therapy. After giving written informed consent, all patients underwent baseline and regular on-treatment measurements of BMD by dual-energy x-ray absorptiometry (DXA) scan, bone turnover and ovarian function by analysis of serum hormone levels and self-reported menstrual diaries. ResultsBaseline lumbar spine BMD in the 41 women given chemotherapy was higher than the normal population (Z score 0.28±0.14 (mean±sem), p=0.047), and fell significantly over the first six months from a mean of 1.05 to 1.01 g/m 2 , p <0.0001, and similar but smaller changes were demonstrated in hip BMD. This fall was independent of age at diagnosis, type of chemotherapy, development of amenorrhoea or either baseline or on-treatment estradiol concentration. During the six months after completion of adjuvant chemotherapy, BMD fell further only in those women with low estradiol or experiencing amenorrhoea during the first six months, although all groups showed evidence of increased bone turnover. ConclusionsThis study demonstrates loss of both spine and hip BMD in pre-menopausal women during six months' adjuvant systemic chemotherapy to be independent of changes in ovarian function. Ovarian function was however related to BMD changes after chemotherapy ceased.3

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Section: Discussioncontrasting

confidence: 86%

Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?

Cameron

Douglas

Brown

et al. 2010

Breast Cancer Res Treat

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“…To better understand the biologic underpinning of how FSH acts on bone, the authors first showed that transgenic mice lacking FSHβ subunit or FSH receptor (FSHR −/− ), although severely hypogonadal, showed no evidence of bone loss (Sun et al 2006). Further evidence for the dependence of bone density on FSH levels was obtained using heterozygotic FSHβ transgenic mice (FSHβ +/− ).…”

Section: New Information On the Direct Roles Of Gonadotrophic Hormonementioning

confidence: 99%

Advances in endocrinology of aging research, 2005–2006

Bellino

2006

Experimental Gerontology

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The purpose of this brief review is to highlight some of the more important advances in endocrinology of aging research over the past year. Four advances were chosen and briefly described. First, exploration of the early steps in the generation of the internal steroidal hormonal signal involved in lifespan extension via the insulin/IGF-like signaling pathway in the nematode by two research groups revealed that the product of cholestanoic acid derivatives metabolized by a cytochrome P-450-like protein activates a protein with homology to the mammalian nuclear receptor superfamily, a process strikingly similar to the steroid hormone signaling pathway documented in mammalian systems. Second is the discovery that sirtuins, proteins that regulate lifespan in model organisms, enhance pancreatic insulin secretion in mice following a glucose challenge, suggesting the potential to regulate mammalian lifespan through regulation of the insulin signaling pathway. Third, the newly discovered hormone klotho, which also plays a role in regulating lifespan, in this case in mice, is reported to not only negatively affect insulin sensitivity but, perhaps more importantly, significantly affects calcium and phosphate metabolism as a required co-factor of Fgf-23 signaling. Finally the gonadotropin FSH is shown to directly affect bone density in mice separate from any direct effect of estrogen, suggesting that reproductive hormones other than estrogen can directly impact menopause-associated pathophysiology in non-reproductive tissues. Keywordsendocrinology of aging; steroidal signaling; cholestanoic acid; sirtuins; insulin secretion; insulin signaling; klotho; gonadotropins; FSH; bone cells; bone density; model organisms Research on endocrinology of aging is quite broad, extending from mechanisms underlying the age-related declines in sex steroid and peptide reproductive and growth hormones, through male and female reproductive aging, and into pathophysiologic effects of age-altered hormone levels on somatic and neuronal tissues and the effects of treatment with exogenous hormones to ameliorate the health declines associated with aging. Several fascinating new or progressing areas of endocrinology of aging research came to light over the past year from about mid-2005 through about mid-2006. This is one perspective, not meant to be a complete survey of all of the research conducted in the area of endocrinology of aging over the past year. Certainly many readers will have their own selection of the highlights over this past year that will differ in whole or in part from those summarized here.Specific areas covered in this brief review are new and exciting findings regarding 1) identification of steroidal ligands involved in hormonal regulation of the lifespan-determining pathway in the nematode model, 2) new findings related to the role of factors involved in * present address: 4899 Elmer Derr Rd.,

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“…Mechanistically, others and we have shown that FSH increases osteoclast formation, function, and survival through a distinct FSHR isoform [9,[26][27][28]. Wu et al [28] further showed that the osteoclastogenic response to FSH was abolished in mice lacking ITAM adapter signaling molecules.…”

Section: Introductionmentioning

confidence: 99%

“…2). As part of this paradigm shift, we later discovered that FSH directly stimulates bone resorption [9]; thus the idea that rising FSH levels during the late peri-menopause could potentially contribute to the bone loss traditionally attributed solely to low estrogen [10]. We are by no means limiting the proven importance of low estrogen in causing bone loss.…”

Section: Introductionmentioning

confidence: 99%