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. 2024 Jul 20;10(7):481.
doi: 10.3390/gels10070481.

A Meta-Analytical Way of Systematizing the Use of Hyaluronan Gels for the Relief of Osteoarthritis, Compared with New Treatment Alternatives

Tudor Pinteala  1   2 , Stelian Sergiu Maier  3 , Norin Forna  1   2 , Liliana Savin  1   2 , Mihnea Theodor Sirbu  1 , Dragos Cristian Popescu  1   4 , Viorel Dan Cionca  4 , Dan Constantin Putineanu  5 , Paul Dan Sirbu  1   2
Affiliations

A Meta-Analytical Way of Systematizing the Use of Hyaluronan Gels for the Relief of Osteoarthritis, Compared with New Treatment Alternatives

Tudor Pinteala et al. Gels. .

Abstract

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for the viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement but for its use adapted to the peculiarities of the disease manifestation and of the patients. A "broad" comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation therapy and its main challenger of clinical interest, the platelet-rich plasma treatment. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using algorithms implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, we adhere in a documented way to the opinion that HA-based products, currently under circumspection, are still clinically useful.

Keywords: hyaluronic acid; meta-analysis; meta-regression; osteoarthritis; platelet-rich plasma; reproducible research; viscosupplementation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The position of injectable treatments in the hierarchy of OA treatment options.
Figure 2
Figure 2
The “wide” meta-analytic comparison of the studies regarding OA pain alleviation, published in the 2014–2023 decade. Studies are inserted in chronological ascending order.
Figure 3
Figure 3
The result of meta-regression applied to the exemplified model that was fitted to the selected studies dedicated to PRP vs. HA efficacy meta-analysis. The gray rhombuses (“diamonds”) represent the confidence intervals corresponding to the individual studies, as predicted by the fitted model. Boundaries of clinical and statistical significance are drawn (the minimal clinically important difference (MCID = −0.37) and 0.8, the limit of high significant effect size) for both areas of favorability of the two types of treatment.
Figure 4
Figure 4
The funnel plots associated with the equal-effects (method=”EE” in rma.uni function of metafor package) meta-regression performed for the exemplifying model discussed in the previous sections of the paper after applying the trim-and-fill procedure. The precision (a) and robustness (b) of studies are depicted as a function of their calculated effect size. Harbord–Egger and Begg–Mazumdar asymmetry tests are included for both pre- and post-adjustment.
Figure 5
Figure 5
The funnel plots associated with the random-effects model (method=”REML” in rma.uni function of metafor package) when the pseudo confidence interval also considers the amount of residual heterogeneity estimated by the model (±1.96SE2+τ^2).
Figure 6
Figure 6
Dynamics of publications related to the use of HA in osteoarthritis and the topics covered during the 2014–2023 decade.
Figure 7
Figure 7
The PRISMA 2020 flow diagram of the collection, screening, and exploiting of information in the analyses carried out in the present work.
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