Evidence map›Paper›PMID 28429052›Full record

ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2017

The skeletal impact of the chemotherapeutic agent etoposide.

A J Koh, B P Sinder, P Entezami, L Nilsson, L K McCauley

Open access · greenAbstract read
In one paragraph

Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

8 citing papers in PubMed, 12 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

5 authors at 1 institution in 1 country.

A J KohPeriodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, 48109-1078, USA.
B P SinderPeriodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, 48109-1078, USA.
P EntezamiPeriodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, 48109-1078, USA.
L NilssonPeriodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, 48109-1078, USA.
L K McCauleyPeriodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, 48109-1078, USA. mccauley@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Tumor microvesicle-mediated modulation of the bone microenvironmentP01CA093900 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIENTA, KENNETH J. · 2004 to 2024
$29.6M
Structure, Composition, & Histology Core - Core BP30AR069620 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARL J JEPSEN · 2016 to 2026
$8.4M
ANABOLIC MECHANISMS OF PTH ACTION IN BONER01DK053904 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MCCAULEY, LAURIE K. · 1998 to 2016
$4.6M
Anabolic Mechanisms of PTH Action in BoneR56DK053904 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MCCAULEY, LAURIE K. · 2018 to 2018
$156k
NCI NIH HHS P01 CA093900NIAMS NIH HHS P30 AR069620NIDDK NIH HHS R01 DK053904NIDDK NIH HHS R56 DK053904
6 · The paper itself

Abstract

Effects of the chemotherapeutic agent etoposide on the skeleton were determined in mice. Numbers of bone marrow cells were reduced and myeloid cells were increased. Bone volume was significantly decreased with signs of inhibition of bone formation. Etoposide after pre-treatment with zoledronic acid still reduced bone but overall bone volume was higher than with etoposide alone.

introductionChemotherapeutics target rapidly dividing tumor cells yet also impact hematopoietic and immune cells in an off target manner. A wide array of therapies have negative side effects on the skeleton rendering patients osteopenic and prone to fracture. This study focused on the pro-apoptotic chemotherapeutic agent etoposide and its short- and long-term treatment effects in the bone marrow and skeleton.

methodsSix- to 16-week-old mice were treated with etoposide (20-25 mg/kg) or vehicle control in short-term (daily for 5-9 days) or long-term (3×/week for 17 days or 6 weeks) regimens. Bone marrow cell populations and their phagocytic/efferocytic functions were analyzed by flow cytometry. Blood cell populations were assessed by CBC analysis. Bone volume and area compartments and osteoclast numbers were measured by microCT, histomorphometry, and TRAP staining. Biomarkers of bone formation (P1NP) and resorption (TRAcP5b) were assayed from serum. Gene expression in bone marrow was assessed using qPCR.

resultsFlow cytometric analysis of the bone marrow revealed short-term etoposide reduced overall cell numbers and B220

conclusionsThese data suggest that etoposide induces apoptosis in the bone marrow and significantly reduces parameters of bone formation with rapid reduction in bone volume. Pre-treatment with an antiresorptive agent results in a preservation of bone mass. Preventive approaches to preserving the skeleton should be considered in human clinical studies.

Indexed as

AnimalsAntineoplastic Agents, PhytogenicApoptosisBlood CellsBone Density Conservation AgentsBone Marrow CellsBone RemodelingDiphosphonatesDrug Administration ScheduleEtoposideFemaleImidazolesMice, Inbred C57BLOsteoporosisTibiaX-Ray MicrotomographyAntineoplastic Agents, PhytogenicBone Density Conservation AgentsDiphosphonatesEtoposideImidazolesZoledronic AcidBisphosphonateBoneChemotherapyEfferocytosisEtoposideMacrophage

Identifiers

PMID28429052
PMCPMC5527337
OpenAlexW2606353528

What OpenQuestion holds

Textmetadata
LicenceTDM
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.