Evidence map›Paper›PMID 25042551›Full record

ArticleOsteoarthritis and cartilage2014

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway.

R G Rosa, K Collavino, A Lakhani, E Delve, J F Weber, A K Rosenthal, S D Waldman

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Osteoarthritis and cartilage, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04303026 (A Randomized Placebo Controlled Trial Testing The Effect of Zoledronic Acid on Hip Osteoarthritis), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 18% 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.

NCT04303026 phase3unknown statusnot on this mapstarted 2020, after this paper: background citation

A Randomized Placebo Controlled Trial Testing The Effect of Zoledronic Acid on Hip Osteoarthritis

TypeinterventionalSponsorVestre Viken Hospital TrustRan2020 to 2024Enrolled70ConditionsOsteoarthritis, HipArmsZoledronic Acid, Saline 0.9%
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 24 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis.Frontiers in cell and developmental biology · 2020
    Review
  6. Article
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

7 authors at 4 institutions in 2 countries.

R G RosaHuman Mobility Research Centre, Kingston General Hospital, Kingston, Ontario, Canada. Electronic address: renata.giardini@gmail.com.
K CollavinoDepartment of Chemical Engineering, Ryerson University, Toronto, Ontario, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address: kristina.collavino@ryerson.ca.
A LakhaniDepartment of Chemical Engineering, Queen's University, Kingston, Ontario, Canada. Electronic address: anand.lakhani@queensu.ca.
E DelveDepartment of Chemical Engineering, Queen's University, Kingston, Ontario, Canada. Electronic address: elizabeth.delve@mail.utoronto.ca.
J F WeberDepartment of Mechanical & Materials Engineering, Queen's University, Kingston, Ontario, Canada. Electronic address: weberj@me.queensu.ca.
A K RosenthalDivision of Rheumatology, Department of Medicine, Medical College of Wisconsin, and the Zablocki VA Medical Center, Milwaukee, WI, USA. Electronic address: ann.rosenthal@va.gov.
S D WaldmanDepartment of Chemical Engineering, Ryerson University, Toronto, Ontario, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address: swaldman@ryerson.ca.
Queen's University · CASt. Michael's Hospital · CAKingston General Hospital · CAMedical College of Wisconsin · US

Funding

ANK-dependent ATP efflux causes calcium pyrophosphate deposition in cartilageI01CX001143 · VA · CLEMENT J. ZABLOCKI VA MEDICAL CENTER · PI ROSENTHAL, ANN K · 2015 to 2018
–
CSRD VA I01 CX001143
6 · The paper itself

Abstract

objectiveBisphosphonates are commonly used anti-osteoporotic drugs which have controversial effects on joint diseases including osteoarthritis. Certain bisphosphonates have been shown to have anabolic effects on cartilage which could have important ramifications for their proposed effects in vivo; however, the underlying mechanisms are poorly understood. Thus, the purpose of this study was to characterize the effects of clodronate on primary articular chondrocyte metabolism and to determine the underlying signaling pathways responsible.

designThe effects of clodronate and pamidronate on extracellular matrix (ECM) biosynthesis, accumulation and MMP-13 activity were observed in high density, 3D cultures of bovine articular chondrocytes for up to 4 weeks were evaluated. Mechanisms were delineated by measuring intracellular Ca(2+) signaling and the effects of pharmacologic inhibition of the purinergic receptor pathway.

resultsClodronate (100 μM) induced an anabolic effect (increased biosynthesis by 13-14%) which resulted in an 89-90% increase in ECM accumulation after 4 weeks of culture and without an associated effect on matrix turn-over. Stimulation by clodronate resulted in a 3.3-fold increase in Ca(2+) signaling and pharmacological inhibitor experiments suggested that the anabolic effects exerted by clodronate are transduced through the purinergic receptor pathway.

conclusionsThese findings support the previous notion that certain bisphosphonates may be useful as adjunctive therapies to potentially ameliorate progression of cartilage degeneration and improve arthritis management.

Indexed as

Anabolic AgentsAnimalsBone Density Conservation AgentsCalcium SignalingCartilage, ArticularCattleCells, CulturedChondrocytesClodronic AcidDiphosphonatesDose-Response Relationship, DrugDrug Evaluation, PreclinicalExtracellular MatrixMatrix Metalloproteinase 13PamidronateReceptors, PurinergicAnabolic AgentsBone Density Conservation AgentsClodronic AcidDiphosphonatesMatrix Metalloproteinase 13PamidronateReceptors, PurinergicAnabolismBisphosphonatesCalcium signalingChondrocytesClodronatePurinergic signaling

Identifiers

PMID25042551
PMCPMC5452978
OpenAlexW2063340108

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.