Evidence map›Paper›PMID 21933863›Full record

ArticleEndocrinology2011

The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors.

Erik R Nelson, Carolyn D DuSell, Xiaojuan Wang, Matthew K Howe, Glenda Evans, Ryan D Michalek, Michihisa Umetani, Jeffrey C Rathmell, Sundeep Khosla, Diane Gesty-Palmer and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
6.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 127 citations in OpenAlex.

  1. 27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019
    Trial
  2. Trial
  3. Multimorbidity patterns among fragility fracture patients aged 50 + years in China and the US.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
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  5. Article
  6. 27-Hydroxycholesterol in cancer development and drug resistance.Journal of enzyme inhibition and medicinal chemistry · 2025
    Review
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  17. Vitamin DScientific reports · 2024
    Article
  18. Article
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  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Erik R NelsonPharmacology and Cancer Biology, Duke University Medical Center, P.O. Box 3813, Durham, North Carolina 27710, USA.
Carolyn D DuSell
Xiaojuan Wang
Matthew K Howe
Glenda Evans
Ryan D Michalek
Michihisa Umetani
Jeffrey C Rathmell
Sundeep Khosla
Diane Gesty-Palmer
Donald P McDonnell
Duke Medical Center · USDuke University Hospital · USMayo Clinic · USDuke University · USThe University of Texas Southwestern Medical Center · US

Funding

SEX STEROIDS, GROWTH FACTORS, &BONE CELL FUNCTIONP01AG004875 · NIA · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 1985 to 2019
$30.8M
UT Southwestern O'Brien Kidney Research Core CenterP30DK079328 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI MOE, ORSON W · 2007 to 2021
$16.9M
Mechanism of Action of Estrogens and AntiestrogensR37DK048807 · NIDDK · DUKE UNIVERSITY · PI MCDONNELL, DONALD P · 2005 to 2014
$5.0M
T cell metabolism as a determinant of differentiation in allergic asthmaR01HL108006 · NHLBI · VANDERBILT UNIVERSITY · PI RATHMELL, JEFFREY C. · 2011 to 2014
$1.5M
Glucose metabolism and cell death in cancerR01CA123350 · NCI · DUKE UNIVERSITY · PI RATHMELL, JEFFREY C. · 2007 to 2011
$1.5M
NCI NIH HHS R01 CA123350NHLBI NIH HHS R01 HL108006NIA NIH HHS AG004875NIA NIH HHS P01 AG004875NIDDK NIH HHS 1P30DK079328NIDDK NIH HHS P30 DK079328NIDDK NIH HHS R37 DK048807NIDDK NIH HHS R37DK048807
6 · The paper itself

Abstract

Osteoporosis and age-related bone loss are important public health concerns. Therefore, there is a high level of interest in the development of medical interventions and lifestyle changes that reduce the incidence of osteoporosis and age-related bone loss. Decreased bone mineral density is associated with high cholesterol, and patients on statins have increased bone mineral densities, strongly implicating cholesterol as a negative regulator of bone homeostasis. In this study, using both molecular and pharmacological approaches, we have been able to demonstrate that the primary cholesterol metabolite, 27-hydroxycholesterol, through its actions on both estrogen receptors and liver X receptors, decreases osteoblast differentiation and enhances osteoclastogenesis, resulting in increased bone resorbtion in mice. Induction of the short heterodimer partner protein by estrogens in osteoblasts can attenuate the liver X receptor-mediated actions of 27-hydroxycholesterol in bone. These data establish a mechanistic link between cholesterol and bone quality, highlight an unexpected target of estrogens in osteoblasts, and define a signaling axis, the therapeutic exploitation of which is likely to yield novel antiosteoporotic drugs.

Indexed as

HomeostasisAnimalsBone and BonesBone ResorptionCell DifferentiationCholesterolHydroxycholesterolsLiver X ReceptorsMiceOrphan Nuclear ReceptorsOsteoblastsOxysterol Binding ProteinsReceptors, EstrogenReceptors, SteroidSterols27-hydroxycholesterolCholesterolHydroxycholesterolsLiver X ReceptorsOrphan Nuclear ReceptorsOxysterol Binding ProteinsReceptors, EstrogenReceptors, SteroidSterols

Identifiers

PMID21933863
PMCPMC3230052
OpenAlexW2073905908

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.