Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 7;22(5):2693.
doi: 10.3390/ijms22052693.

The Rationale for the Intra-Articular Administration of Clodronate in Osteoarthritis

Antimo Moretti  1 , Marco Paoletta  1 , Sara Liguori  1 , Walter Ilardi  1 , Francesco Snichelotto  1 , Giuseppe Toro  1 , Francesca Gimigliano  2 , Giovanni Iolascon  1
Affiliations
Review

The Rationale for the Intra-Articular Administration of Clodronate in Osteoarthritis

Antimo Moretti et al. Int J Mol Sci. .

Abstract

Background: Several pharmacological therapeutic approaches have been proposed to manage osteoarthritis (OA), including intra-articular (IA) injections. Although the discovery of clodronate, a bisphosphonate, dates back to the 1960s and the effects of its IA administration have been investigated for decades in animal models, mechanisms of action of this drug are not quite clear, particularly in OA. This scoping review is an overview of the biological as well as the clinical role of clodronic acid in OA.

Method: A scoping review based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model was performed to characterize the mechanisms of action of IA clodronate in OA and to evaluate its efficacy from a clinical point of view.

Results: Several effects of clodronate have been observed in animal models of OA, including depletion of synovial lining cells that results in reduced production of chemokines (IL-1, TNF- α), growth factors (TGF-β, BMP 2/4), and metalloproteases (MMP 2/3/9); prevention of cartilage damage, synovial hyperplasia, and proteoglycans loss; reduction in joint inflammation, joint swelling, and osteophyte formation. From a clinical perspective, patients with knee OA treated with IA clodronate experienced improvements in pain and joint mobility.

Conclusion: Clodronate appears to have different mechanisms of action interfering with the pathogenic processes contributing to OA development and progression. This intervention demonstrated positive effects for patients affected by knee OA.

Keywords: clodronate; clodronic acid; diphosphonates; injections; intra-articular; osteoarthritis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) flow-chart for study selection.
Figure 2
Figure 2
Mechanisms of action of clodronic acid in intra-articular environment.
See this image and copyright information in PMC

References

    1. March L., Cross M., Lo C. Osteoarthritis: A Serious Disease: Submitted to the U.S. Food and Drug Administration. [(accessed on 2 January 2021)]; Available online: https://www.oarsi.org/sites/default/files/docs/2016/oarsi_white_paper_oa....
    1. Iolascon G., Gimigliano F., Moretti A., De Sire A., Migliore A., Brandi M.L., Piscitelli P. Early osteoarthritis: How to define, diagnose, and manage. A systematic review. Eur. Geriatr. Med. 2017;8:383–396. doi: 10.1016/j.eurger.2017.07.008. - DOI
    1. Huffman K.F., Thornhill T.H. Osteoarthritis and Its Management: What the Physician Assistant Needs to Know. Physician Assist. Clin. 2021;6:23–40. doi: 10.1016/j.cpha.2020.08.003. - DOI
    1. Kellgren J.H., Lawrence J.S. Radiological Assessment of Osteo-Arthrosis. Ann. Rheum. Dis. 1957;16:494–502. doi: 10.1136/ard.16.4.494. - DOI - PMC - PubMed
    1. Kolasinski S.L., Neogi T., Hochberg M.C., Oatis C., Guyatt G., Block J., Callahan L., Copenhaver C., Dodge C., Felson D., et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res. (Hoboken) 2020;72:149–162. doi: 10.1002/acr.24131. - DOI - PMC - PubMed