Evidence map›Paper›PMID 38956196›Full record

Trial reportNature medicine2024

Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.

Joshua N Farr, Elizabeth J Atkinson, Sara J Achenbach, Tammie L Volkman, Amanda J Tweed, Stephanie J Vos, Ming Ruan, Jad Sfeir, Matthew T Drake, Dominik Saul and 8 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase II
In one paragraph

Trial report in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04313634 (Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans), which is not on this map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
–field-weighted citation impact
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.

NCT04313634 phase2completednot on this map

Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans: A Phase 2, Single-Center, 20-week, Open-Label, Randomized Controlled Trial.

TypeinterventionalSponsorSundeep Khosla, M.D.Ran2020 to 2023Enrolled74ConditionsHealthyArmsDasatinib, Quercetin, Fisetin
3 · Its place in the literature

Who cites it

82 citing papers in PubMed.

  1. Trial
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  4. Review
  5. Article
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  9. The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026
    Review
  10. Review
  11. The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026
    Review
  12. Observational
  13. Review
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  15. Article
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  19. The gut-bone-inflammation axis: intestinal barrier disruption as a central driver of osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Review
  20. Article

22 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

18 authors.

Joshua N FarrDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA. farr.joshua@mayo.edu.ORCID http://orcid.org/0000-0002-3179-6414
Elizabeth J AtkinsonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Sara J AchenbachDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Tammie L VolkmanDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Amanda J TweedDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Stephanie J VosDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Ming RuanDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Jad SfeirDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-1576-1534
Matthew T DrakeDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Dominik SaulDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-0673-3710
Madison L DoolittleDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Irina BancosDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Kai YuDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-8794-0318
Tamara TchkoniaRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-4623-7145
Nathan K LeBrasseurRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-2002-0418
James L KirklandDepartment of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-1676-4905
David G MonroeDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-4818-0114
Sundeep KhoslaDivision of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA. khosla.sundeep@mayo.edu.ORCID http://orcid.org/0000-0002-2936-4372

Funding

Targeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla, Nathan K LeBrasseur · 2019 to 2026
$28.7M
Effect of Aging on Preadipocyte DifferentiationR37AG013925 · NIA · MAYO CLINIC ROCHESTER · PI KIRKLAND, JAMES L. · 2016 to 2025
$6.6M
Translational Geroscience NetworkR33AG061456 · NIA · MAYO CLINIC ROCHESTER · PI JAMES L. KIRKLAND, STEPHEN B. KRITCHEVSKY · 2019 to 2026
$6.2M
Senescence and Growth Differentiation Factors as Modifiers of AgingR01AG055529 · NIA · MAYO CLINIC ROCHESTER · PI LEBRASSEUR, NATHAN K · 2018 to 2022
$3.1M
Defining the interactions of senescent immune cells and skeletal cellsR01AG076515 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla, David G Monroe · 2022 to 2026
$2.4M
Targeting Cellular Senescence and RAGE in Type 2 DiabetesR01DK128552 · NIDDK · UNIVERSITY OF ARIZONA · PI FARR, JOSHUA NICHOLAS · 2021 to 2025
$2.0M
The Role of miR-219a-5p in Bone MetabolismR01AG063707 · NIA · MAYO CLINIC ROCHESTER · PI MONROE, DAVID G · 2020 to 2024
$1.5M
Targeting cellular senescence with senolytics to improve skeletal health in older humansR21AG065868 · NIA · MAYO CLINIC ROCHESTER · PI FARR, JOSHUA NICHOLAS, KHOSLA, SUNDEEP · 2020 to 2021
$419k
NIA NIH HHS P01 AG062413NIA NIH HHS R01 AG055529NIA NIH HHS R01 AG063707NIA NIH HHS R01 AG076515NIA NIH HHS R21 AG065868NIA NIH HHS R33 AG061456NIA NIH HHS R37 AG013925NIDDK NIH HHS R01 DK128552U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01 AG 062413U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R33 AG61456U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R37 AG13925
6 · The paper itself

Abstract

Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%, P = 0.020) and 4 weeks (+16%, P = 0.024), but was not different from control at 20 weeks (-9%, P = 0.149). No serious adverse events were observed. In exploratory analyses, the skeletal response to D + Q was driven principally by women with a high senescent cell burden (highest tertile for T cell p16 (also known as CDKN2A) mRNA levels) in which D + Q concomitantly increased P1NP (+34%, P = 0.035) and reduced CTx (-11%, P = 0.049) at 2 weeks, and increased radius bone mineral density (+2.7%, P = 0.004) at 20 weeks. Thus, intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women. However, our exploratory analyses indicate that further studies are needed testing the hypothesis that the underlying senescent cell burden may dictate the clinical response to senolytics. ClinicalTrials.gov identifier: NCT04313634 .

Indexed as

Bone and BonesPostmenopauseQuercetinAgedBiomarkersBone DensityBone ResorptionCellular SenescenceCollagen Type ICyclin-Dependent Kinase Inhibitor p16DasatinibFemaleHumansMiddle AgedPeptide FragmentsPeptidesBiomarkersCDKN2A protein, humanCollagen Type Icollagen type I trimeric cross-linked peptideCyclin-Dependent Kinase Inhibitor p16DasatinibPeptide FragmentsPeptidesProcollagenprocollagen Type I N-terminal peptideQuercetinSenotherapeutics

Identifiers

PMID38956196
PMCPMC11705617

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Registered trials

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.