Regulation of bone turnover by sex steroids in men

Arunik Sanyal, Kelley A. Hoey, Ulrike I. Mödder, Jesse L. Lamsam, Louise K. McCready, James M. Peterson, Sara J. Achenbach, Merry Jo Oursler, Sundeep Khosla

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Introduction: The mechanism(s) by which sex steroids regulate bone turnover in humans are unclear, and recent studies have suggested that follicle-stimulating hormone (FSH) may play an important role in regulating bone resorption. Materials and Methods: Fifty-nine men (median age, 69 yr) underwent suppression of sex steroids using a gonadotropin-releasing hormone (GnRH) agonist and aromatase blocker and were replaced with testosterone (T; 5 mg/d) and estradiol (E; 37.5 μg/d). After assessment of bone resorption markers (serum C-terminal telopeptide of type I collagen [CTX] and TRACP5b), they were randomized to sex steroid deficiency (-T, -E), E alone (-T, +E), T alone (+T, -E), or both (+T, +E) and restudied 3 wk later. Bone marrow aspirates were obtained to isolate osteoblastic, T, and monocytic cells using magnetic-activated cell sorting. Results: Serum CTX and TRACP5b increased significantly (by 71% and 15%, p < 0.01 and < 0.001, respectively) in the -T, -E group, and these increases occurred despite a 60% suppression of serum FSH levels (p < 0.001) caused by the GnRH agonist. There were significant E (but not T) effects on preventing increases in serum CTx and TRACP levels. There was a nonsignificant trend (p = 0.122) for E to suppress RANKL mRNA levels in bone marrow osteoblastic cells. Changes in mRNA levels for other cytokines (TNF-α, interleukin (IL)-1α, IL-1β, IL-1ra, IFN-γ) in bone marrow cells were not significant. Conclusions: E has greater suppressive effects on bone resorption than T, and increased bone resorption after sex steroid deficiency can occur independently of changes in FSH secretion. E effects on bone resorption may be mediated by regulation of RANKL production by osteoblastic cells, although further studies using more highly purified cells may reduce the variability of the mRNA measurements and allow for clearer definition of the mediators of sex steroid action in vivo.

Original languageEnglish (US)
Pages (from-to)705-714
Number of pages10
JournalJournal of Bone and Mineral Research
Volume23
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Bone Remodeling
Bone Resorption
Steroids
Follicle Stimulating Hormone
Interleukin-1
Gonadotropin-Releasing Hormone
Bone Marrow Cells
Messenger RNA
Serum
Aromatase
Interleukins
Testosterone
Estradiol
Biomarkers
Bone Marrow
Cytokines

Keywords

  • Bone turnover
  • Cytokines
  • Male osteoporosis
  • RANKL

ASJC Scopus subject areas

  • Surgery

Cite this

Sanyal, A., Hoey, K. A., Mödder, U. I., Lamsam, J. L., McCready, L. K., Peterson, J. M., ... Khosla, S. (2008). Regulation of bone turnover by sex steroids in men. Journal of Bone and Mineral Research, 23(5), 705-714. https://doi.org/10.1359/jbmr.071212

Regulation of bone turnover by sex steroids in men. / Sanyal, Arunik; Hoey, Kelley A.; Mödder, Ulrike I.; Lamsam, Jesse L.; McCready, Louise K.; Peterson, James M.; Achenbach, Sara J.; Oursler, Merry Jo; Khosla, Sundeep.

In: Journal of Bone and Mineral Research, Vol. 23, No. 5, 05.2008, p. 705-714.

Research output: Contribution to journalArticle

Sanyal, A, Hoey, KA, Mödder, UI, Lamsam, JL, McCready, LK, Peterson, JM, Achenbach, SJ, Oursler, MJ & Khosla, S 2008, 'Regulation of bone turnover by sex steroids in men', Journal of Bone and Mineral Research, vol. 23, no. 5, pp. 705-714. https://doi.org/10.1359/jbmr.071212
Sanyal A, Hoey KA, Mödder UI, Lamsam JL, McCready LK, Peterson JM et al. Regulation of bone turnover by sex steroids in men. Journal of Bone and Mineral Research. 2008 May;23(5):705-714. https://doi.org/10.1359/jbmr.071212
Sanyal, Arunik ; Hoey, Kelley A. ; Mödder, Ulrike I. ; Lamsam, Jesse L. ; McCready, Louise K. ; Peterson, James M. ; Achenbach, Sara J. ; Oursler, Merry Jo ; Khosla, Sundeep. / Regulation of bone turnover by sex steroids in men. In: Journal of Bone and Mineral Research. 2008 ; Vol. 23, No. 5. pp. 705-714.
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AU - Hoey, Kelley A.

AU - Mödder, Ulrike I.

AU - Lamsam, Jesse L.

AU - McCready, Louise K.

AU - Peterson, James M.

AU - Achenbach, Sara J.

AU - Oursler, Merry Jo

AU - Khosla, Sundeep

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N2 - Introduction: The mechanism(s) by which sex steroids regulate bone turnover in humans are unclear, and recent studies have suggested that follicle-stimulating hormone (FSH) may play an important role in regulating bone resorption. Materials and Methods: Fifty-nine men (median age, 69 yr) underwent suppression of sex steroids using a gonadotropin-releasing hormone (GnRH) agonist and aromatase blocker and were replaced with testosterone (T; 5 mg/d) and estradiol (E; 37.5 μg/d). After assessment of bone resorption markers (serum C-terminal telopeptide of type I collagen [CTX] and TRACP5b), they were randomized to sex steroid deficiency (-T, -E), E alone (-T, +E), T alone (+T, -E), or both (+T, +E) and restudied 3 wk later. Bone marrow aspirates were obtained to isolate osteoblastic, T, and monocytic cells using magnetic-activated cell sorting. Results: Serum CTX and TRACP5b increased significantly (by 71% and 15%, p < 0.01 and < 0.001, respectively) in the -T, -E group, and these increases occurred despite a 60% suppression of serum FSH levels (p < 0.001) caused by the GnRH agonist. There were significant E (but not T) effects on preventing increases in serum CTx and TRACP levels. There was a nonsignificant trend (p = 0.122) for E to suppress RANKL mRNA levels in bone marrow osteoblastic cells. Changes in mRNA levels for other cytokines (TNF-α, interleukin (IL)-1α, IL-1β, IL-1ra, IFN-γ) in bone marrow cells were not significant. Conclusions: E has greater suppressive effects on bone resorption than T, and increased bone resorption after sex steroid deficiency can occur independently of changes in FSH secretion. E effects on bone resorption may be mediated by regulation of RANKL production by osteoblastic cells, although further studies using more highly purified cells may reduce the variability of the mRNA measurements and allow for clearer definition of the mediators of sex steroid action in vivo.

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