title: 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.
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.
authors.affiliation: Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. christian.kirschneck@ukr.de.
authors.forename: Christian
authors.identifier: 0000-0001-9473-8724
authors.initials: C
authors.lastname: Kirschneck
authors.affiliation: Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Meier
authors.affiliation: Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bauer
authors.affiliation: Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Proff
authors.affiliation: Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.|Anatomical Institute, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Fanghänel
mesh_terms: D000293:Adolescent; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D009970:Orthodontics; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000187:drug effects / Q000473:pathology*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012391:Root Resorption / Q000188:drug therapy*; D013270:Stomach / Q000187:drug effects; D013843:Thiazines / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014087:Tooth Movement Techniques; D014092:Tooth Root / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D053244:Osteoprotegerin; D053245:RANK Ligand; D013843:Thiazines; D013844:Thiazoles; D002097:C-Reactive Protein; D000077239:Meloxicam
keywords: Anti-inflammatory agents; Periodontal ligament; Rats; Root resorption; Tooth movement