25 June 2023: Review Articles
A Review of Preclinical and Clinical Studies in Support of the Role of Non-Steroidal Anti-Inflammatory Drugs in Dentistry
Anna Kotowska-Rodziewicz 1ABCDEFG , Anna Zalewska 1ABCDEF , Mateusz Maciejczyk 2ABCDEFG*DOI: 10.12659/MSM.940635
Med Sci Monit 2023; 29:e940635
Table 1 Preclinical and clinical studies that have supported the role of non-steroidal anti-inflammatory drugs (NSAIDs) in dentistry.
| Study design | Results | Endpoints | References |
|---|---|---|---|
| Nine drugs including 3 NSAIDs: piroxicam, lysine acetylsalicylate and diclofenac sodium were used in the in vitro study. Twenty-seven dentin discs of extracted human molars, adjusted to the thickness of 5 mm, were cleaned of the smear layer and placed in a suitable tube. Then, 50 ml of the drug and 500 ml of water were added to the discs. Next, an ultraviolet-visible spectrophotometer was used to detect the infiltrated drug after 10, 20, 30, 60, 120, 180, and 240 minutes | Lysine acetylsalicylate demonstrated the best dentin permeability among the 3 NSAIDs | Lysine acetylsalicylate, due to its best penetration into the dentin, has the potential for topical use in pulp inflammation | []105 |
| 42 Swiss mice were divided into 7 groups: controls; amoxicillin; amoxicillin/clavulanate; erythromycin; acetaminophen; ibuprofen and celecoxib, to inhibit cyclooxygenase 2 (COX-2). SEM-EDX analysis was conducted on all cusps of the third molars. Calcium (Ca), phosphorus (P), aluminum, potassium, sodium, magnesium and chlorine were quantified. The stoichiometric Ca/P molar ratios were calculated. Immunohistochemical quantification of COX-2 in incisors was carried out by image analysis using COX-2-specific immunostaining | Groups treated with antibiotics showed no significant differences in the content of the chemical elements. Only acetaminophen and celecoxib showed a significant decrease in Ca and P compared to the control samples. There were no differences in Ca/P ratios. Groups treated with amoxicillin, amoxicillin/clavulanate, erythromycin and acetaminophen showed significantly lower amounts of immunoreactive COX-2 at the enamel maturation stage of incisors in mice | COX-2 is involved in the maturation phase of enamel. NSAIDs, due to their COX-2 inhibition, may affect enamel mineralization during the maturation phase | []209 |
| Medication histories of 225 patients with oral lichen planus were compared to the histories of 202 age- and gender-matched control patients who were treated in the same clinics | 17% of patients with lichen planus were taking nonsteroidal anti-inflammatory drugs (NSAIDs) compared to 9% of control patients. Nearly 30% of patients with the more severe erosive form of lichen planus were taking NSAIDs, while less than 9% of patients without erosions were taking this type of medication, which indicates a correlation between NSAIDs and the more severe form of lichen planus. Withdrawal from NSAIDs resulted in resolution or marked clinical improvement in 12 of the patients studied | NSAIDs can exacerbate the form of lichen planus, and their discontinuation may be beneficial in treating the disease in some patients | []158 |
| 80 patients with conditions affecting the oral cavity, characterized by an inflammatory component qualifying for analgesic and anti-inflammatory treatment were randomized 1: 1 – the first group (N=40) was given a mouthwash containing 0.103% diclofenac epolamine (DHEP) in aqueous solution, and the second group was offered a mouthwash containing 0.074% diclofenac free acid in aqueous solution. Study subjects rinsed their mouth for 1 minute with 15 ml of the mouthwash twice a day, for 7 days. The effectiveness of the therapy was evaluated 3 and 7 days after the start of the study with an assessment of the pain scale and an evaluation of inflammation | The mouthwash containing DHEP was at least as effective as diclofenac in relieving pain and inflammation and equally well tolerated by patients | Diclofenac-containing rinses relieve oral pain and inflammation | []140 |
| Fifteen medically healthy subjects (7 males and 8 females), each with 2 sites requiring periodontal surgery of similar complexity, type and duration were instructed to take ibuprofen prior to one of the surgery procedures. A standard bleeding time and papillary bleeding index score were recorded during an initial consultation, and prior to the first and second procedure. The volume of aspirated blood was measured during each surgery by subtracting the amount of water used for irrigation from the total volume of fluid (blood + irrigation water) collected at 15-minute intervals during the surgery | Intraoperative blood loss was shown to increase almost twice in patients taking ibuprofen before the procedure compared to those who did not take the drug | Ibuprofen taken before periodontal surgery increases intraoperative blood loss in patients | []198 |
| 60 patients who presented pericoronitis and who did not undergo surgery within 7 consecutive days. The patients were randomly assigned to 3 groups and were treated with oral diclofenac (N=20), oral flurbiprofen (N=20) and topical benzydamine (N=20). Oral Health-Related Quality-of-Life (OHQoL) measure was assessed for all study participants with a self-reported eight-item scale that was developed to evaluate pericoronitis. The total OHQoL scores were calculated for each day during the seven-day study period | The study group treated with topical benzydamine had a significantly greater improvement in the OHQoL scores compared to the oral diclofenac and oral flurbiprofen groups within the first 4 days | Topical application of benzydamine is an effective alternative to oral NSAIDs | []139 |
| A group of 28 patients requiring periodontal surgery was randomly assigned to receive either selective COX-2 inhibitor (N=14) or steroidal anti-inflammatory drug (N=14) 60 minutes before the surgical procedure. To examine patient anxiety, a Corah’s dental anxiety scale was applied before surgery. The extent of pain/discomfort during the trans-operative period and immediately after the surgery was measured via a visual analog scale. Additionally, intensity of pain/discomfort and edema were examined 4, 8, 12, and 24 h postoperatively | With regard to anxiety, no significant differences between the groups were observed (p>0.05). With respect to the extent of pain/discomfort during the trans-operative, immediate and late postoperative period, data demonstrated no significant differences (p>0.05) between the COX-2 inhibitor and steroidal groups. For edema, intragroup analysis did not reveal any statistically significant difference (p>0.05) within 24 h following surgery in each group | Both COX-2 selective inhibitors and steroid drugs presented similar potential in relieving pain and swelling after periodontal procedures. NSAIDs perform well in relieving pain and swelling after periodontal procedures | []164 |
| Three NSAIDs (indomethacin, tolmetin and mefenamic acid) were incorporated into polymethylmethacrylate bone cement (PMMA) strips in a range of concentrations; their cytotoxicity, pattern of drug release and ability to suppress elevated levels of prostaglandin E2 in cultured human periodontal ligament fibroblasts (HPLF) were assessed | Strips released between 10% and 30% of the total incorporated drug over 7 days, with the highest levels released by strips containing 20% w/w of the drug. Strips containing 20% indomethacin and mefenamic acid released in excess of toxic levels in the first 24 h. Strips containing 20%, 10%, and 5% w/w NSAID significantly (P | Topical use of NSAIDs is an important element of periodontal disease therapy | []163 |
| The study group consisted of 15 patients with periodontitis. Eight patients received 50 mg flurbiprofen b.i.d. for 2 months, and 7 patients received placebo in this double-blind study. Alveolar bone height was determined using standardized radiography and alveolar bone metabolism was assessed using 99m-Tc uptake prior to dosing and 2 months later | Radiopharmaceutical uptake was significantly reduced in the alveolar bone of teeth undergoing active bone loss at the beginning of the study in patients receiving flurbiprofen (p | NSAIDs have an inhibitory effect on bone destruction in periodontitis processes | []157 |
| The study included 25 patients with both lower third molars showing the same degree of wedging on X-ray. They were divided into 2 groups: the first group received 7.5 mg meloxicam every 12 h for 36 h, starting an hour before the surgery, and the second group received 100 mg nimesulide every 12 h for the same period of time. Both groups received 750 mg paracetamol which the subjects were to take according to the guidelines if the pain increased. The first extraction of one of the 2 lower third molars was performed. After 2 weeks, the eighth teeth of the contralateral side were extracted, followed by an introduction of drug substitution in the groups. The first group received nimesulide, and the second one – meloxicam. Each Treatment was followed by evaluation of trismus, swelling, and pain | Edema occurred in both study groups but was more pronounced in patients treated with meloxicam. Trismus was less frequent in patients taking nimesulide. A better analgesic effect was demonstrated by nimesulide vs meloxicam | NSAIDs used after surgical removal of retained teeth reduce swelling and pain, and reduce the incidence of trismus | []131 |
| All patients treated in a university faculty postgraduate dental clinic between 1979 and 2012 that had experienced implant failure and had had a dental implant removed surgically (292 implants in 168 patients) were contacted to solicit additional information about their present dental and medical status and frequency of current and past use of NSAIDs | 104 patients with initially 468 implants had experienced 238 implant failures, of which 197 were due to failure in osseointegration (42%). 60 of the participants, initially with 273 implants, had used NSAIDs perioperatively and experienced 44% implant failures versus 38% in the non-NSAID cohort. The NSAID cohort experienced 3.2 times more cases of radiographic bone loss greater than 30% of the vertical height of their remaining implants and 1.9 times more cases of cluster failures, defined as failure of 50% or more of the implant(s) placed | NSAIDs may adversely affect bone healing and osteointegration of dental implants | []137 |
| Male Wistar rats (n=90) were randomly divided into 3 groups: C (control) (N=30), non-steroidal anti-inflammatory drug (NSAID; potassium diclofenac) (N=30) and steroidal anti-inflammatory drug (SAID; dexamethasone sodium phosphate) (N=30). The control group animals of received 0.9% saline solution, the NSAID group was given potassium diclofenac CATAFLAM (5 mg/kg) and the SAID group received dexamethasone sodium phosphate DEXANIL (2 mg/kg). The animals were sacrificed 3, 7, or 14 days after placement of the orthodontic appliance. The upper first molars were processed histologically | The results showed that, in 3 and 7 days, NSAID and SAID groups had fewer blood vessels, Howship lacunae, and osteoclast-like cells compared to the control group. On the 7t and 14 day, there was a lower percentage of mature collagen in the SAID group (P | NSAIDs can adversely affect the bone remodeling process during orthodontic treatment | []145 |
| A total of 45 patients about to undergo fixed appliance orthodontic treatment were enrolled in this double-blind prospective study. Patients were evenly and randomly divided in a blinded manner, into 3 groups: paracetamol/acetaminophen 500 mg 3 times daily (N=15); placebo in the form of empty capsules (N=15); and etoricoxib 60 mg once daily (N=15). Drug administration began an hour before initiating the bonding procedure and archwire placement, and the drug was given until day 3. The pain perceived was recorded by the patients on a linear and graded Visual Analog Scale at the following time intervals: 2 h after insertion of the appliance, 6 h thereafter and again at night-time of the day of the appointment; then 24 h later and on the 2 day at night-time; 48 h after the appointment and on the 3 day at night-time | Etoricoxib at a dose of 60 mg was found to be most effective in relieving pain during orthodontic treatment with fixed braces | NSAIDs are effective in alleviating pain associated with orthodontic treatment by means of fixed braces | []141 |
| Cells were treated with plasmatic concentrations of ASA and celecoxib | Both treatments provoked a discrete inhibitory effect on cell viability and modulated interleukin 6 (IL-6) production. The mRNA expression of several cytokines, chemokines, chemokine receptors and other chemotaxis-related genes were modulated after treatment with ASA and celecoxib | NSAIDs inhibit the metastatic potential of head and neck squamous cell carcinoma cells. Exposure to NSAIDs shows protective effects against head and neck cancer | []173 |
| ASA – acetylsalicylic acid; COX-2 – cyclooxygenase; DHEP – diclofenac epolamine; HPLF – human periodontal ligament fibroblasts; LPS – lipopolysaccharide; NSAIDs – non-steroidal anti-inflammatory drugs; OHOoL – Oral Health-Related Quality-of-Life; PGE 2 – prostaglandin 2; PMMA – polymethylmethacrylate bone cement; SAIDs – steroidal anti-inflammatory drugs. | |||