Efficacy and Safety of Hyaluronan Treatment in Combination Therapy With Home Exercise for Knee Osteoarthritis Pain

Stitik, Todd P.; Blacksin, Marcia F.; Stiskal, Doreen; Kim, Jong H.; Foye, Patrick M.; Schoenherr, Lisa; Choi, Eun-Seok; Chen, Boqing; Saunders, Howard J.; Nadler, Scott F.

doi:10.1016/j.apmr.2006.11.006

Cited by 31 publications

(32 citation statements)

References 31 publications

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“…The net result is a tissue milieu with increased levels of inflammatory mediators that lead to cellular stress, chondrocyte apoptosis and loss of matrix tissue [ 5 - 9 ]. There is clinical evidence to support the beneficial effects of controlled moderate exercise in relieving adults with OA, in combination with chondroprotective agents [ 49 , 50 ]. However, the success of these treatments largely relies on the validation of the drugs and their pathophysiological interactions within the OA affected joint.…”

Section: Discussionmentioning

confidence: 99%

Dynamic compression counteracts IL-1β induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs

et al. 2008

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BackgroundNitric oxide and prostaglandin E2 (PGE2play pivotal roles in both the pathogenesis of osteoarthritis and catabolic processes in articular cartilage. These mediators are influenced by both IL-1β and mechanical loading, and involve alterations in the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX)-2 enzymes. To identify the specific interactions that are activated by both types of stimuli, we examined the effects of dynamic compression on levels of expression of iNOS and COX-2 and involvement of the p38 mitogen-activated protein kinase (MAPK) pathway.MethodsChondrocyte/agarose constructs were cultured under free-swelling conditions with or without IL-1β and/or SB203580 (inhibitor of p38 MAPK) for up to 48 hours. Using a fully characterized bioreactor system, constructs were subjected to dynamic compression for 6, 12 and 48 hours under similar treatments. The activation or inhibition of p38 MAPK by IL-1β and/or SB203580 was analyzed by western blotting. iNOS, COX-2, aggrecan and collagen type II signals were assessed utilizing real-time quantitative PCR coupled with molecular beacons. Release of nitrite and PGE2 was quantified using biochemical assays. Two-way analysis of variance and the post hoc Bonferroni-corrected t-test were used to examine data.ResultsIL-1β activated the phosphorylation of p38 MAPK and this effect was abolished by SB203580. IL-1β induced a transient increase in iNOS expression and stimulated the production of nitrite release. Stimulation by either dynamic compression or SB203580 in isolation reduced the IL-1β induced iNOS expression and nitrite production. However, co-stimulation with both dynamic compression and SB203580 inhibited the expression levels of iNOS and production of nitrite induced by the cytokine. IL-1β induced a transient increase in COX-2 expression and stimulated the cumulative production of PGE2 release. These effects were inhibited by dynamic compression or SB203580. Co-stimulation with both dynamic compression and SB203580 restored cytokine-induced inhibition of aggrecan expression. This is in contrast to collagen type II, in which we observed no response with the cytokine and/or SB203580.ConclusionThese data suggest that dynamic compression directly influences the expression levels of iNOS and COX-2. These molecules are current targets for pharmacological intervention, raising the possibility for integrated pharmacological and biophysical therapies for the treatment of cartilage joint disorders.

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Section: Discussionmentioning

confidence: 99%

Dynamic compression counteracts IL-1β induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs

et al. 2008

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“…Sixteen RCTs investigating analgesia with HA products were identified with a systematic literature search . The outcome measure of interest was change from baseline (CFB) in pain at movement (0 − 100 mm visual analogue scale).…”

Section: Illustrative Examplementioning

confidence: 99%

Network meta‐analysis of longitudinal data using fractional polynomials

Jansen

Vieira²,

Cope³

2015

Statistics in Medicine

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Network meta-analysis of randomized controlled trials (RCTs) are often based on one treatment effect measure per study. However, many studies report data at multiple time points. Furthermore, not all studies measure the outcomes at the same time points. As an alternative to a network meta-analysis based on a synthesis of the results at one time point, a network meta-analysis method is presented that allows for the simultaneous analysis of outcomes at multiple time points. The development of outcomes over time of interventions compared in an RCT is modeled with fractional polynomials, and the differences between the parameters of these polynomials within a trial are synthesized across studies with a Bayesian network meta-analysis. The proposed models are illustrated with an analysis of RCTs evaluating interventions for osteoarthritis of the knee. Fixed and random effects second order fractional polynomials were applied to the case study. Network meta-analysis with models that represent the treatment effects in terms of several parameters using fractional polynomials can be considered a useful addition to models for network meta-analysis of repeated measures previously proposed. When RCTs report treatment effects at multiple follow-up times, these models can be used to synthesize the results even if reporting times differ across the studies.

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“…[28][29][30][31][32][33][34][35] Primary outcome measures in studies demonstrating the efficacy of HA injection are typically average self-report scores of knee symptoms and function. 30,32,34,36 The effect of HA injection on kinematic and kinetic variables of the lower extremity joints and that of muscle activation patterns, however, have not been extensively examined. 37,38 The rate of OA progression at the knee may be modified through improved movement patterns and tolerance of physical activity resulting from viscosupplementation.…”

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Medial knee joint loading increases in those who respond to hyaluronan injection for medial knee osteoarthritis

Briem

Axe

Snyder‐Mackler

2009

Journal Orthopaedic Research

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Knee osteoarthritis (OA) is a cause of decline in function and the medial compartment is often affected. Intraarticular injection of hyaluronic acid (HA) is indicated as a symptom modifying treatment with at least 6 months passing between consecutive injection series. The effects of HA injection on gait variables have not been extensively examined. Therefore, our objective was to investigate the effects of HA injection on gait in people with medial knee OA. Twenty-seven subjects were included; each was tested prior to treatment (baseline), no later than 3 weeks following the last injection (post-HA), and again 5 months after treatment ended (follow-up). Responder criteria were defined to identify responders and non-responders. Subjects underwent 3D gait analysis, muscle activity was sampled, and co-contraction indices were calculated. Responders experienced increased peak knee adduction moments post-HA, whereas non-responders did not. Improved selfreport scores were associated with increased knee adduction moments and increased medial co-contraction. Pain relief may result in higher loading onto the already vulnerable medial compartment due to changes in lower limb mechanics and muscle activation patterns. Eventually this may result in a more rapid progression of joint deterioration. ß

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Efficacy and Safety of Hyaluronan Treatment in Combination Therapy With Home Exercise for Knee Osteoarthritis Pain

Cited by 31 publications

References 31 publications

Dynamic compression counteracts IL-1β induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs

Dynamic compression counteracts IL-1β induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs

Network meta‐analysis of longitudinal data using fractional polynomials

Medial knee joint loading increases in those who respond to hyaluronan injection for medial knee osteoarthritis

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