Evidence map›Paper›PMID 27631553›Full record

ArticleEndocrinology2016

The Bone Sparing Effects of 2-Methoxyestradiol Are Mediated via Estrogen Receptor-α in Male Mice.

Anna L Eriksson, Anna S Wilhelmson, Johan B Fagman, Henrik Ryberg, Antti Koskela, Juha Tuukkanen, Åsa Tivesten, Claes Ohlsson

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 21% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

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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

8 authors at 4 institutions in 3 countries.

Anna L ErikssonCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
Anna S WilhelmsonCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
Johan B FagmanCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
Henrik RybergCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
Antti KoskelaCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
Juha TuukkanenCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
Åsa TivestenCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
Claes OhlssonCenter for Bone and Arthritis Research (A.L.E., H.R., C.O.), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., A.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Sahlgrenska Cancer Center (J.F.), Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Clinical Chemistry (H.R.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Unit of Cancer Research and Translational Medicine (A.K., J.T.), Medical Research Center, Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-900 14 Oulu, Finland.
National Academy of Medicine · USUniversity of Gothenburg · SEUniversity of Oulu · FISahlgrenska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

2-Methoxyestradiol (2ME2), a metabolite of 17β-estradiol (E2), exerts bone sparing effects in animal models. We hypothesized that the underlying mechanism is back conversion of 2ME2 to E2, which subsequently acts via estrogen receptor (ER)α. We measured serum E2 levels in orchidectomized wild-type (WT) mice treated with 2ME2 66.6 μg/d or placebo. In placebo-treated animals, E2 was below the detection limit. In 2ME2-treated mice, the serum E2 level was 4.97 ± 0.68 pg/mL. This corresponds to the level found in diesterus in cycling female mice. Next, we investigated bone parameters in orchidectomized WT and ERα knockout mice treated with 2ME2 or placebo for 35 days. 2ME2 (6.66 μg/d) preserved trabecular and cortical bone in WT mice. Trabecular volumetric-bone mineral density was 64 ± 20%, and trabecular bone volume/total volume was 60 ± 20% higher in the metaphyseal region of the femur in the 2ME2 group, compared with placebo (P < .01). Both trabecular number and trabecular thickness were increased (P < .01). Cortical bone mineral content in the diaphyseal region of the femur was 31 ± 3% higher in the 2ME2 group, compared with placebo (P < .001). This was due to larger cortical area (P < .001). Three-point bending showed an increased bone strength in WT 2ME2-treated animals compared with placebo (maximum load [Fmax] +19±5% in the 2ME2 group, P < .05). Importantly, no bone parameter was affected by 2ME2 treatment in ERα knockout mice. In conclusion, 2ME2 treatment of orchidectomized mice results in increased serum E2. ERα mediates the bone sparing effects of 2ME2. The likely mediator of this effect is E2 resulting from back conversion of 2ME2.

Indexed as

2-MethoxyestradiolAnimalsBody WeightBone and BonesBone DensityCancellous BoneCortical BoneEstradiolFemaleMaleMiceMice, KnockoutOrchiectomyOrgan SizeReceptors, EstrogenTestosterone2-MethoxyestradiolEstradiolReceptors, EstrogenTestosterone

Identifiers

PMID27631553
PMCPMC5086527
OpenAlexW2519215526

What OpenQuestion holds

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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.