Evidence map›Paper›PMID 30406161›Full record

ArticleBone reports2018

Cathepsin K inhibition preserves compressive load in lumbar vertebrae of osteoporotic monkeys.

Isabel D Colón-Bernal, Le T Duong, Brenda Pennypacker, James Henderson, Kenneth M Kozloff, Mark M Banaszak Holl

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Bone reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Isabel D Colón-BernalChemistry Department, University of Michigan, Ann Arbor, MI, USA.
Le T DuongBone Biology Group, Merck & Co., Inc., West Point, PA, USA.
Brenda PennypackerBone Biology Group, Merck & Co., Inc., West Point, PA, USA.
James HendersonCenter for Statistical Consultation and Research (CSCAR), University of Michigan, Ann Arbor, MI, USA.
Kenneth M KozloffDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Mark M Banaszak HollDepartment of Chemical Engineering, Monash University, Melbourne, Australia.
University of Michigan · USUnited States Military Academy · USMonash University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anti-resorptive drugs treat bone loss by blocking osteoclast activity through a variety of mechanisms of action. Once significant bone loss has occurred, the ability to restore biomechanical function may differ based on the drug chosen. To assess this question, bisphosphonate (alendronate, ALN) and cathepsin K inhibitor (MK-0674, CatKi) were employed in treatment mode to compare the relative changes to cancellous bone microstructure and mechanical properties in ovariectomized (OVX) cynomolgus monkeys. Lumbar vertebrae (LV) bone mineral density (BMD) values taken two years post-surgery prior to drug treatment show a 10-15% decrease (p < 0.05) for all OVX animals. OVX animals were then treated with vehicle (VEH), ALN (0.03 mg/kg weekly), or CatKi MK-0674 (0.6 or 2.5 mg/kg daily, CatKi-L and H respectively) for two years and compared to a control Sham surgery group. Ex-vivo microcomputed tomography (μCT) of LV2 and compression testing of LV4-6 were used to measure cancellous bone microstructure and changes in bone mechanics, respectively. After two years of treatment, ALN-treated animals showed no significant difference in μCT or biomechanical parameters when compared to Veh. However, treatment with CatKi-H resulted in a 30% increase in yield and peak loads, and apparent peak and yield stress as compared to Veh (p < 0.05) and gave average mechanical values greater than the Sham sample. Treatment with CatKi-L exhibited a similar trend of increase to CatKi-H (p < 0.08). Intriguingly, these changes were realized despite no significant differences in mean values of trabecular bone morphologic parameters. Together these data suggest matrix-level changes in bone composition that are unique to the CatK inhibition mechanism, resulting in the preservation of bone compressive load with treatment.

Indexed as

AlendronateCathepsin-kMicro computed tomographyOsteoporosis

Identifiers

PMID30406161
PMCPMC6214835
OpenAlexW2897980155

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.