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Meloxicam medication reduces orthodontically induced dental root resorption and tooth movement velocity: a combined in vivo and in vitro study of dental-periodontal cells and tissue

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Abstract

Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate pain sensations during orthodontic therapy but are also assumed to interfere with associated pseudo-inflammatory reactions. In particular, the effects of partially selective COX-2 inhibition over the constitutively expressed COX-1 (11:1) on periodontal cells and tissue, as induced by the NSAID meloxicam, remain unclear. We investigate possible adverse side-effects and potentially useful beneficial effects during orthodontic therapy and examine underlying cellular and tissue reactions. We randomly assigned 63 male Fischer344 rats to three consecutive experiments of 21 animals each (cone-beam computed tomography; histology/serology; reverse-transcription quantitative real-time polymerase chain reaction) in three experimental groups (n = 7; control; orthodontic tooth movement [OTM] of the first/second upper left molars [NiTi coil spring, 0.25 N]; OTM with a daily oral meloxicam dose of 3 mg/kg). In vitro, we stimulated human periodontal ligament fibroblasts (hPDL) with orthodontic pressure (2 g/cm2) with/without meloxicam (10 μM). In vivo, meloxicam significantly reduced serum C-reactive protein concentration, tooth movement velocity, orthodontically induced dentine root resorption (OIRR), osteoclast activity and the relative expression of inflammatory/osteoclast marker genes within the dental-periodontal tissue, while presenting good gastric tolerance. In vitro, we observed a corresponding significant decrease of prostaglandin E2/interleukin-6/RANKL(−OPG) expression and of hPDL-mediated osteoclastogenesis. By inhibiting prostaglandin synthesis, meloxicam seems to downregulate hPDL-mediated inflammation, RANKL-induced osteoclastogenesis and, consequently, tooth movement velocity by about 50%, thus limiting its suitability for analgesia during orthodontic therapy. However, its protective effects regarding OIRR and good tolerance profile suggest future prophylactic application, which merits its further investigation.

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Acknowledgments

The authors thank Dr. med. dent. Michael Maurer and medical technical assistant Mrs. Eva Zaglauer for their contribution and assistance and the ReForM-A-research funding program of the Faculty of Medicine of the University of Regensburg (Kirschneck 03-31-2015) for their financial support.

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Authors and Affiliations

  1. Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Christian Kirschneck, Matthias Meier, Kathrin Bauer, Peter Proff & Jochen Fanghänel

  2. Anatomical Institute, Ernst-Moritz-Arndt University, Greifswald, Germany

    Jochen Fanghänel

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  1. Christian Kirschneck
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  2. Matthias Meier
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  3. Kathrin Bauer
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  4. Peter Proff
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  5. Jochen Fanghänel
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Corresponding author

Correspondence to Christian Kirschneck.

Ethics declarations

This work was performed and reported in accordance with the ethical standards of the institutional ethics committee (approval ID 12-170-0150) and the corresponding national authorities (approval ID 54–2532.1-46/13), the 1964 Helsinki declaration and its later amendments and comparable ethical standards including the obtaining of informed consent for the use of human material. All applicable international, national and/or institutional guidelines for the care and use of animals were followed, as were the Uniform Standards for manuscripts submitted to biomedical journals (ICMJE) and the official NC3Rs ARRIVE guidelines for the Reporting of In Vivo Experiments in Animal Research (Kilkenny et al. 2010).

Conflict of interest

The authors report no financial or other conflict of interest relevant to this article, which is the intellectual property of the authors. This paper has been approved by all authors and the affiliated institution. Furthermore, no part of this article has previously been published or is being considered for publication elsewhere. Some of the results, however, were used for the fulfilment of a scientific qualification by the author Matthias Meier in 2015. Control groups 1 and 2 (control/OTM) and corresponding results have been/are being used in other publications to minimize unnecessary animal suffering.

Funding source

This work was supported by a ReForM-A grant from the ReForM research funding programme of the Faculty of Medicine of the University of Regensburg, Germany (Kirschneck 03-31-2015).

Additional information

Chemical compound investigated (NCBI PubChem Compound database)

Meloxicam (PubChemCID: 54677470).

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Kirschneck, C., Meier, M., Bauer, K. et al. Meloxicam medication reduces orthodontically induced dental root resorption and tooth movement velocity: a combined in vivo and in vitro study of dental-periodontal cells and tissue. Cell Tissue Res 368, 61–78 (2017). https://doi.org/10.1007/s00441-016-2553-0

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