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/cm) 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 E/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.

Sodium‐chloride‐induced effects on the expression profile of human periodontal ligament fibroblasts with focus on simulated orthodontic tooth movement

“…At the end of the experiment, we washed stimulated PDLFs with PBS and added a macrophage osteoclast‐precursor cell line (RAW264.7 cells; CLS Cell Lines Service, Eppelheim, Germany) at a concentration of 70,000 cells per well . The resulting co‐culture was then incubated for 3 d under cell‐culture conditions , enabling induction of RANKL‐mediated osteoclastogenesis by PDLFs . Histochemical tartrate‐resistant acid phosphatase (TRAP) staining (red) was used to detect differentiated osteoclast‐like cells .…”

“…Histochemical tartrate‐resistant acid phosphatase (TRAP) staining (red) was used to detect differentiated osteoclast‐like cells . Tartrate‐resistant acid phosphatase‐positive cells were assessed by a blinded observer at a magnification of ×100 with an Olympus IX50 microscope (Olympus, Hamburg, Germany) in 10 random fields of view per well (biological replicate) and the arithmetic mean number of TRAP‐positive cells was used for further analysis .…”

“…Periodontal ligament fibroblasts are known to react to orthodontic compressive forces by triggering a local sterile pseudoinflammatory immunological process within the periodontal ligament, thus enabling orthodontic tooth movement via increased release of prostaglandins synthesized by enhanced expression and activity of cyclooxygenase‐2 (COX‐2) . This leads to enhanced secretion of proinflammatory cytokines, such as interleukin (IL)‐6, as well as the formation of soluble and membrane‐linked receptor activator of nuclear factor kappa‐B ligand (RANKL) and osteoclastogenesis . Furthermore, mechanically stimulated PDLFs secrete matrix metalloproteinases , which are responsible for degradation of the extracellular matrix , thus inducing the necessary transformation for orthodontic tooth movement.…”

“…Both orthodontic tooth movement and periodontitis can be modulated by a plethora of systemic and exogenous factors. In particular, drugs such as non‐steroidal anti‐inflammatory drugs (NSAIDs) , toxic influences such as nicotine , and nutritional components such as alcohol , can have a major impact on the velocity of orthodontic tooth movement and progression of periodontitis, as well as associated phenomena, such as undesired inflammatory dental‐root resorption, either propagating these processes by increased osteoclastogenesis and matrix degradation, or inhibiting them. On the other hand, in the future, pharmacologically active substances could also potentially be used therapeutically to support orthodontic and periodontal therapy by increasing velocity of tooth movement or by preventing root resorption , bone loss , and orthodontic relapse , during or after treatment.…”

Caracterização Das Reabsorções Radiculares Inflamatórias Interna E Externa: Nível De Conhecimento Dos Profissionais Acerca Do Diagnóstico Diferencial

“…A manutenção do processo de reabsorção depende de fatores de estimulação das células osteoclásticas, como infecção ou pressão. A ausência de tais estímulos promove a cessação do processo reabsortivo 4 .…”