Intra-articular dexamethasone to inhibit the development of post-traumatic osteoarthritis

Alan J. Grodzinsky, Yang Wang, Sanjeev Kakar, Mark S. Vrahas, Christopher H. Evans

Research output: Contribution to journalReview article

29 Scopus citations

Abstract

Injury to the joint provokes a number of local pathophysiological changes, including synthesis of inflammatory cytokines, death of chondrocytes, breakdown of the extra-cellular matrix of cartilage, and reduced synthesis of matrix macromolecules. These processes combine to engender the subsequent development of post-traumatic osteoarthritis (PTOA). To prevent this from happening, it is necessary to inhibit these disparate responses to injury; given their heterogeneity, this is challenging. However, dexamethasone has the necessary pleiotropic properties required of a drug for this purpose. Using in vitro models, we have shown that low doses of dexamethasone sustain the synthesis of cartilage proteoglycans while inhibiting their breakdown after injurious compression in the presence or absence of inflammatory cytokines. Under these conditions, dexamethasone is non-toxic and maintains the viability of chondrocytes exposed chronically to such cytokines as interleukin (IL) -1, IL-6, and tumor necrosis factor-α. Moreover, the anti-inflammatory properties of dexamethasone have been appreciated for decades. In view of this information, we have initiated a pilot clinical study to determine whether a single, intra-articular injection of dexamethasone into the wrist shows promise in preventing PTOA after intra-articular fracture of the distal radius. CLINICAL SIGNIFICANCE: Suppressing the various etiopathophysiological responses to injury in the joint is an attractive strategy for lowering the clinical burden of PTOA. The intra-articular administration of dexamethasone soon after injury offers a simple and inexpensive means of accomplishing this.

Original languageEnglish (US)
Pages (from-to)406-411
Number of pages6
JournalJournal of Orthopaedic Research
Volume35
Issue number3
DOIs
StatePublished - Mar 1 2017

Keywords

  • cartilage
  • hand and wrist
  • pathophysiology
  • synovium and osteoarthritis
  • trauma

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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