title: Intra-articular dexamethasone to inhibit the development of post-traumatic osteoarthritis.
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.
  
  
  
  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. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:406-411, 2017.
authors.affiliation: Departments of Biological, Electrical and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
authors.affiliation: Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Vrahas
authors.affiliation: Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Evans
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000008:administration & dosage*; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007596:Joints / Q000293:injuries*; D010003:Osteoarthritis / Q000209:etiology / Q000517:prevention & control*; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone
keywords: cartilage; hand and wrist; pathophysiology; synovium and osteoarthritis; trauma