Dataset Information

Sympathetic β1-adrenergic signaling contributes to regulation of human bone metabolism.

ABSTRACT:

Background

Evidence from rodent studies indicates that the sympathetic nervous system (SNS) regulates bone metabolism, principally via β2-adrenergic receptors (β2-ARs). Given the conflicting human data, we used multiple approaches to evaluate the role of the SNS in regulating human bone metabolism.

Methods

Bone biopsies were obtained from 19 young and 19 elderly women for assessment of ADRB1, ADRB2, and ADRB3 mRNA expression. We examined the relationship of β-blocker use to bone microarchitecture by high-resolution peripheral quantitative CT in a population sample of 248 subjects. A total of 155 postmenopausal women were randomized to 1 of 5 treatment groups for 20 weeks: placebo; propranolol, 20 mg b.i.d.; propranolol, 40 mg b.i.d.; atenolol, 50 mg/day; or nebivolol, 5 mg/day. We took advantage of the β1-AR selectivity gradient of these drugs (propranolol [nonselective] << atenolol [relatively β1-AR selective] < nebivolol [highly β1-AR selective]) to define the β-AR selectivity for SNS effects on bone.

Results

ADRB1 and ADRB2, but not ADRB3, were expressed in human bone; patients treated clinically with β1-AR-selective blockers had better bone microarchitecture than did nonusers, and relative to placebo, atenolol and nebivolol, but not propranolol, reduced the bone resorption marker serum C-telopeptide of type I collagen (by 19.5% and 20.6%, respectively; P < 0.01) and increased bone mineral density of the ultradistal radius (by 3.6% and 2.9%; P < 0.01 and P < 0.05, respectively).

Conclusions

These 3 independent lines of evidence strongly support a role for adrenergic signaling in the regulation of bone metabolism in humans, principally via β1-ARs.

Trial registration

ClinicalTrials.gov NCT02467400.

Funding

This research was supported by the NIH (AG004875 and AR027065) and a Mayo Clinic Clinical and Translational Science Award (CTSA) (UL1 TR002377).

SUBMITTER: Khosla S

PROVIDER: S-EPMC6205387 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Sympathetic β1-adrenergic signaling contributes to regulation of human bone metabolism.

Khosla Sundeep S Drake Matthew T MT Volkman Tammie L TL Thicke Brianne S BS Achenbach Sara J SJ Atkinson Elizabeth J EJ Joyner Michael J MJ Rosen Clifford J CJ Monroe David G DG Farr Joshua N JN

The Journal of clinical investigation 20181002 11

<h4>Background</h4>Evidence from rodent studies indicates that the sympathetic nervous system (SNS) regulates bone metabolism, principally via β2-adrenergic receptors (β2-ARs). Given the conflicting human data, we used multiple approaches to evaluate the role of the SNS in regulating human bone metabolism.<h4>Methods</h4>Bone biopsies were obtained from 19 young and 19 elderly women for assessment of ADRB1, ADRB2, and ADRB3 mRNA expression. We examined the relationship of β-blocker use to bone m ...[more]

PMID: 30153111

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Dataset Information

Sympathetic β1-adrenergic signaling contributes to regulation of human bone metabolism.

Background

Methods

Results

Conclusions

Trial registration

Funding

Publications

Sympathetic β1-adrenergic signaling contributes to regulation of human bone metabolism.

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