Comparison of Intra-articular Injection of Hyaluronic Acid and <i>N</i>-Acetyl Cysteine in the Treatment of Knee Osteoarthritis: A Pilot Study

Özçamdallı, Mustafa; Mısır, Abdülhamit; Kızkapan, Turan Bilge; Uzun, Erdal; Duygulu, Fuat; Yazıcı, Cevat; Kafadar, İbrahim Halil

doi:10.1177/1947603516675915

Cited by 19 publications

(27 citation statements)

References 40 publications

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“…Moreover, NAC reduced cartilage degradation markers and exhibited comparable beneficial effects to hyaluronic acid after a single i.a. injection in patients suffering from mild to moderate knee OA [13].…”

Section: Discussionmentioning

confidence: 99%

Initial Harm Reduction by N-Acetylcysteine Alleviates Cartilage Degeneration after Blunt Single-Impact Cartilage Trauma in Vivo

Riegger

Leucht

Palm³

et al. 2019

IJMS

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Joint injuries are highly associated with the development of post-traumatic osteoarthritis. Previous studies revealed cell- and matrix-protective effects of N-acetylcysteine (NAC) after ex vivo cartilage trauma, while chondroanabolic stimulation with bone morphogenetic protein 7 (BMP7) enhanced type II collagen (COL2) expression. Here, as a next step, we investigated the combined and individual efficacy of intra-articular antioxidative and chondroanabolic treatment in a rabbit in vivo cartilage trauma model. Animals were randomly divided into group A (right joint: trauma (T); left joint: T+BMP7) and group B (right joint: T+NAC; left joint: T+BMP7+NAC). Condyles were impacted with the use of a spring-loaded impact device to ensure defined, single trauma administration. After 12 weeks, histopathological analysis was performed and the presence of matrix metalloproteinase 13 (MMP-13) and COL2 was assessed. Trauma-induced hypocellularity, MMP-13 expression, and cell cluster formation were reduced in NAC-treated animals. In contrast, BMP7 further increased cluster formation. Moreover, synovial concentrations of COL2 carboxy propeptide (CPII) and proteoglycan staining intensities were enhanced in NAC- and NAC+BMP7-treated joints. For the first time, the efficacy of NAC regarding early harm reduction after blunt cartilage trauma was demonstrated in vivo. However, parallel administration of BMP7 was not significantly superior compared to NAC alone.

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Section: Discussionmentioning

confidence: 99%

Initial Harm Reduction by N-Acetylcysteine Alleviates Cartilage Degeneration after Blunt Single-Impact Cartilage Trauma in Vivo

Riegger

Leucht

Palm³

et al. 2019

IJMS

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“…Of these, 57 included data for IA HA mono-injection 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70. At the end, 28 studies were included,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 whereas 29 studies were removed for 1 or several of the following reasons:Two studies were in combination with surgery: anterior cruc...…”

Section: Resultsmentioning

confidence: 99%

“…Eight with experimental regimens from a multi-injection product: single-shot,26, 27, 28 or large shot grouping several syringes,29, 30, 31 or smaller shot, 32 or retreatment 33 ;…”

Section: Resultsmentioning

confidence: 99%

Intra-Articular Hyaluronic Acid in the Symptomatic Treatment of Knee Osteoarthritis: A Meta-Analysis of Single-Injection Products

Vincent¹

2019

Current Therapeutic Research

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Background Viscosupplementation of the synovial fluid with intra-articular hyaluronic acid (IA HA) is a well-known symptomatic treatment of knee osteoarthritis. The question arises whether a monoinjection (ie, single injection) could be as efficient as multi-injection (ie, 3–5 injections) regimens. Methods A meta-analysis of published studies relating to IA HA monoinjection trials was performed. The efficacy criterion was the Western Ontario and MacMaster Universities pain subscore. Any study design was accepted, from randomized control trials to single-arm observational open-label studies. An extensive search was performed using PubMed, Google, Google Scholar, and references found in recent meta-analyses, for all articles published before end of April 2018. Population profiles were analyzed in terms of age, sex, body mass index (BMI), and Kellgren-Lawrence (KL) radiology grades. Results of intra-articular single injection of placebo were collected to create a database allowing post hoc comparisons. Each IA HA study arm was compared to an IA placebo arm (either pooled or not), to present a similar KL profile controlled with the χ 2 test. The effect size (ES) (95% CI) and P values were calculated and synthesized for each follow-up visit at 1, 2, 3, and 6 months. In parallel, a global approach was used to represent the variations from baseline for each group or subgroup studied. Results From 1547 citations, 28 studies were included in the meta-analysis, representing 4129 patients treated with monoinjection: 3360 received IA HA and 769 patients received IA placebo. The mean (SD) IA HA patient was 61.2 (9.6) years, 63% women, BMI 28.0 (4.1), 47% KL III, and 3% KL IV. A good placebo KL profile matching was obtained for 26 of the 31 IA HA arms. For the whole IA HA population, ES = 0.30 (95% CI, 0.25–0.35) at 3 months and ES = 0.39 (95% CI, 0.33–0.44) at 6 months. In a restricted analysis, after removal of outliers, poorly KL matched and active arms <30 patients, results remained unchanged, ES = 0.29 (95% CI, 0.23–0.34) and ES = 0.40 (95% CI, 0.34–0.45) at 3 and 6 months respectively, whilst heterogeneity was improved. Conclusions There are certainly limits to the post hoc placebo comparison method, for individual studies. But for each synthesis per subgroup or group, the results were properly confirmed using multiple statistical approaches and weighing methods. This meta-analysis suggests that monoinjections produce results similar to multi-injections of IA HA in terms of pain relief in the treatment of knee osteoarthritis. ( Curr Ther Res Clin Exp . 2019; 80:XXX–XXX)

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“…Regarding the hypothesis that NAC retards the inflammation process, long-term treatment with oral NAC was found to cause no significant reduction in the activity of neutrophilic inflammatory biomarkers in patients with cystic fibrosis [25]. However, in a pilot study, Ozcamdalli compared the efficacies between intra-articular injections of HA or NAC in the treatment of knee OA and revealed that NAC had outcomes comparable to those of HA in terms of pain and function scales, but biomarkers within or between groups exhibited equivocal results [10].…”

Section: Discussionmentioning

confidence: 99%

“…According to experimental and tissue culture studies, NAC is effective in clearing free-oxygen radicals, slowing the cartilage degradation process, reducing synovial inflammation, and reducing pain. In addition, one recent study confirmed that NAC use in patients with knee OA yielded more effective pain relief and better functional outcomes compared with intra-articular injection of HA [ 10 ]. However, few studies have examined the therapeutic effects of NAC on OA.…”

Section: Introductionmentioning

confidence: 99%

Increased risk of knee osteoarthritis in patients using oral N-acetylcysteine: a nationwide cohort study

Yeh

Liang

Chang

et al. 2020

BMC Musculoskelet Disord

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Background: Knee osteoarthritis (OA) is known to be a progressive degenerative disorder; however, recent evidence suggests that inflammatory mediators contribute to cartilage degradation. Studies have reported that Nacetylcysteine (NAC) had a promising effect on the reduction of the synthesis of proinflammatory and structural mediators by synovial cells. Given the lack of relevant clinical trials, we conducted this study to determine the relationship between NAC use and risk of knee OA. Methods: We designed a retrospective cohort study from 2000 to 2013. Patients who received oral NAC over 28 days within 1 year after the first prescription were defined as the case group, whereas those without NAC use were considered as candidates of the control group. We adopted 1:4 propensity-score matching by age, sex, index year, and comorbidities to obtain the control group. The primary outcome was a new diagnosis of knee OA during the follow-up period. Results: Our study sample comprised 12,928 people who used NAC and 51,715 NAC nonusers. NAC users had a significantly higher incidence of osteoarthritis (adjusted hazard ratio: 1.42, P < .001) than did NAC nonusers. Also, in analyses stratified by age group and sex, all subgroups exhibited a significantly higher incidence of knee osteoarthritis (P < .0001) among NAC users than among NAC nonusers. The use of oral NAC was associated with nearly four-fold increased the risk of knee OA in the young age group. Conclusions: Long-term use of oral NAC is associated with a higher risk of knee OA.

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Comparison of Intra-articular Injection of Hyaluronic Acid and N-Acetyl Cysteine in the Treatment of Knee Osteoarthritis: A Pilot Study

Cited by 19 publications

References 40 publications

Initial Harm Reduction by N-Acetylcysteine Alleviates Cartilage Degeneration after Blunt Single-Impact Cartilage Trauma in Vivo

Initial Harm Reduction by N-Acetylcysteine Alleviates Cartilage Degeneration after Blunt Single-Impact Cartilage Trauma in Vivo

Intra-Articular Hyaluronic Acid in the Symptomatic Treatment of Knee Osteoarthritis: A Meta-Analysis of Single-Injection Products

Increased risk of knee osteoarthritis in patients using oral N-acetylcysteine: a nationwide cohort study

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