The Effect of Estrogen, Beta-adrenergic Agonist and Antagonist on Bone Metabolism in Healthy Postmenopausal Women

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-222
Annegreet G Veldhuis-Vlug*1, Erik Endert1, Annemieke C Heijboer2, Michael W. Tanck1, Paul Lips2, Berthe L van Eck-Smit1, Eric Fliers3 and Peter H Bisschop3
1Academic Medical Center Amsterdam, Amsterdam, Netherlands, 2VU University Medical Center, Amsterdam, Netherlands, 3Academic Medical Center, Amsterdam, Netherlands
Introduction: Animal experiments indicate that the sympathetic nervous system (SNS) controls bone remodeling. Osteoblast-specific beta-2 adrenergic receptor (B2AdrR) knockout mice are characterized by a high-bone mass phenotype and are protected from bone loss after ovariectomy. In addition, pharmacological inhibition and stimulation of the B2AdrR results in high and low bone mass, respectively (1-4). The results from epidemiological studies in humans on the association of beta-blocker treatment and fracture risk are inconsistent (reviewed in (5)). Therefore we conducted a randomized controlled trial to investigate the effects of beta-agonist and beta-antagonist and their interaction with estrogen on human bone metabolism.  

Design and Setting:This multi-arm parallel randomized controlled trial was performed at the Endocrine Department of the Academic Medical Center of the University of Amsterdam in The Netherlands from 2010 until 2012.

Subjects:32 healthy postmenopausal women who had their last menstrual cycle 12 to 60 months ago were recruited from the general population. Exclusion criteria were contraindications to the study treatment and diseases or medications influencing bone metabolism.

Intervention: Participants (n=8 per group) were randomized to receive treatment with 1] 17-beta estradiol (E2) 2 mg qd, 2] E2 2 mg qd and terbutaline 5 mg qd, 3] propranolol SR 80 mg qd or 4] no treatment during 12 weeks.

Outcome measure:The main outcome measure was the difference in serum concentrations of the bone resorption marker C-terminal crosslinking telopeptides of collagen type I (CTx) and the bone formation marker procollagen type I N propeptide (P1NP) compared in the treatment and control groups after 12 weeks.

Results: CTx and P1NP at baseline were not different between groups. CTx and P1NP were lower during 12 weeks of E2 compared to control (mean difference at 12 weeks: CTx 175 ng/L or 54% change (p=0.008), P1NP 21 ug/L or 33% change (p=0.000)). For CTx the maximal effect was already observed after four weeks of treatment. Addition of beta-agonist to estrogen or beta-antagonist treatment had no effect on CTx and P1NP concentrations.

Conclusion: Estrogen treatment decreased bone turnover as expected already within 4 weeks. Beta-antagonist treatment and addition of beta-agonist treatment to estrogen had no effect on bone turnover. Therefore we could not confirm the effect of pharmacological beta-adrenergic stimulation or inhibition on human bone remodeling.

Trial registration number: Netherlands Trial Registry TC 2874

Funding: This work was supported by The Netherlands Organization for Health Research and Development (ZonMw) Ref: 90700308.

Disclosure: The authors have nothing to disclose.

1.   Ducy P, Amling M, Takeda S et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000; 100(2):197-207.    2.   Takeda S, Elefteriou F, Levasseur R et al. Leptin regulates bone formation via the sympathetic nervous system. Cell 2002; 111(3):305-317.    3.   Elefteriou F, Ahn JD, Takeda S et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005; 434(7032):514-520.    4.   Bonnet N, Benhamou CL, Malaval L et al. Low dose beta-blocker prevents ovariectomy-induced bone loss in rats without affecting heart functions. J Cell Physiol 2008; 217(3):819-827.    5.   Wiens M, Etminan M, Gill SS, Takkouche B. Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies. J Intern Med 2006; 260(4):350-362.

Nothing to Disclose: AGV, EE, ACH, MWT, PL, BLV, EF, PHB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The Netherlands Organization for Health Research and Development (ZonMw) Ref: 90700308.