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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-?. 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.

SUBMITTER: Grodzinsky AJ

PROVIDER: S-EPMC5604325 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Grodzinsky Alan J AJ Wang Yang Y Kakar Sanjeev S Vrahas Mark S MS Evans Christopher H CH

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20170302 3

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. Howeve ...[more]

PMID: 27176565

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Project description:ObjectivesTo quantify fracture severity for a series of displaced intra-articular calcaneal fractures (DIACFs) and to correlate it with Sanders classification, post-traumatic osteoarthritis (PTOA), and patient outcomes.DesignRetrospective review and fracture severity analysis.SettingLevel 1 trauma center affiliated with the University of Iowa in Iowa City, IA.Patients/participantsThirty-six patients with 48 DIACFs were selected from 153 patients previously treated. All patients 18 years of age and older who had available electronic preop and postop computed tomography (CT) scans, good-quality postop and follow-up radiographs, and a follow-up ≥18 months were selected for study.InterventionFractures were treated with percutaneous reduction, using multiple small stab incisions and fluoroscopy to guide manipulation of articular fragments using cork screws or Steinmann pins, with subsequent fixation using 3.5- and 4.0-mm screws.Main outcome measurementsPreop CT scans were used to grade fractures according to the Sanders classification and to quantify fracture severity. Fracture severity was objectively quantified using a CT-based measure of fracture energy. PTOA was assessed on follow-up radiographs using the Kellgren-Lawrence scale. Patient outcomes were assessed using the Short Form 36 (SF-36) questionnaire and a visual analog scale pain score.ResultsFracture energies for the 48 DIACFs ranged from 14.1 to 26.2 J (19.3 ± 3.1 J) and correlated with Sanders classification (rho = 0.53, P = 0.0001); type I (16.3 ± 0.9 J); type II (18.0 ± 2.7 J); type III (20.8 ± 2.8 J); and type IV (22.0 ± 0.7 J). Fracture energy was higher for fractures in which the subtalar joint developed PTOA (19.5 ± 2.7 J) than for those that did not (18.9 ± 3.3 J), but the difference did not reach statistical significance. The Sanders classification predicted PTOA risk [odds ratio (OR) = 4.04, 95% confidence interval = 1.43-11.39, P = 0.0084]. No relationship was observed between fracture energy and visual analog scale pain scores. Higher fracture energy correlated with lower SF-36 scores.ConclusionsFracture energy positively correlates with Sanders classification for DIACFs, which can be used to identify more severe fractures at greater risk of progressing to PTOA.Level of evidencePrognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Project description:Background/objectiveOxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model.MethodsTwelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 ?L of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks (n = 5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment.ResultsGait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time (p = 0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group (p = 0.047, Mann-Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups (p > 0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20-26) and 20 (range, 9-26), respectively (p = 0.382, Mann-Whitney U test).ConclusionIntra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.

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

Publications

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

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