Non-Cochrane · intervention · PM41578912
Cyclooxygenase-2 selective inhibitors increase the risk of alveolar osteitis: A systematic review and meta-analysis.
Isiordia-Espinoza M-A, Hernández-Gómez A, Bologna-Molina R, et al. · Medicina oral, patologia oral y cirugia bucal · 2026 · PubMed · doi:10.4317/medoral.27577
Findings
Population Patients undergoing simple exodontia or third molar surgery
17 findings
| Aspirin | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 0.49 [0.23, 1.02] GRADE not reported 1 study · 181 participants |
| Diclofenac | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 1.83 [0.67, 5.04] GRADE not reported 3 studies · 641 participants |
| Ibuprofen | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 0.72 [0.46, 1.13] GRADE not reported 7 studies · 1166 participants |
| Ketorolac | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 1.53 [0.72, 3.24] GRADE not reported 4 studies · 397 participants |
| Naproxen sodium | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 0.88 [0.43, 1.78] GRADE not reported 4 studies · 503 participants |
| Celecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 0.28 [0.15, 0.52] GRADE not reported 3 studies · 682 participants |
| Etoricoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 1.16 [0.59, 2.29] GRADE not reported 3 studies · 784 participants |
| Traditional NSAIDs, all drugs combined | Placebo or untreated control | Alveolar osteitis (dry socket) Overall analysis | The subgroup and the overall analyses showed no statistical difference in the risk of alveolar osteitis (no overall estimate reported) GRADE not reported 19 studies · 2888 participants |
| Parecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 1.75 [0.93, 3.27] GRADE not reported 3 studies · 962 participants |
| Rofecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence Sensitivity analysis excluding Fricke 2002 | OR 1.59 [0.92, 2.77] GRADE not reported 4 studies · 824 participants |
| Rofecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence Sensitivity analysis excluding Malmstrom 2002 | OR 1.83 [1.05, 3.18] GRADE not reported 4 studies · 752 participants |
| Rofecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence Sensitivity analysis excluding Chang 2002 | OR 2.00 [1.18, 3.41] GRADE not reported 4 studies · 763 participants |
| Rofecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 1.89 [1.15, 3.10] 6.40 [2.10, 10.70] % (absolute risk increase) GRADE not reported 5 studies · 947 participants |
| Rofecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence Sensitivity analysis excluding Daniels 2006 | OR 2.22 [1.21, 4.07] GRADE not reported 4 studies · 623 participants |
| COX-2 selective inhibitors, all drugs combined | Placebo or untreated control | Alveolar osteitis (dry socket) Overall analysis | Overall results showed no statistical difference (no overall estimate reported) GRADE not reported 13 studies · 3820 participants |
| Rofecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence Sensitivity analysis excluding Korn 2004 | OR 1.89 [1.11, 3.24] GRADE not reported 4 studies · 826 participants |
| Valdecoxib | Placebo or untreated control | Alveolar osteitis (dry socket) occurrence | OR 1.21 [0.60, 2.47] GRADE not reported 2 studies · 445 participants |
Included primary studies 49
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Malmstrom 2002 A comparison of rofecoxib versus celecoxib in treating pain after dental surgery: A single-center, randomized, double-blind, placebo- and… DOI:10.1016/s0149-2918(02)80059-5 | 2002 | 1 other review | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Malmstrom 2002 A comparison of rofecoxib versus celecoxib in treating pain after dental surgery: a single-center, randomized, double-blind, placebo- and… PMID:12462285 | 2002 | 1 other review | not stated | not extracted yet |
| Al-Sukhun 2011 matched by author and year (probable) | NR | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Al-Sukhun 2011 The cyclooxygenase-2 inhibitor celecoxib and alveolar osteitis. PMID:21413548 | 2011 | this review only | not stated | not extracted yet |
| Chang 2002 Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: A… DOI:10.1016/s0149-2918(02)85126-8 | 2002 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Chang 2002 Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: a… PMID:12017395 | 2002 | this review only | not stated | not extracted yet |
| Christensen 2011 A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar… DOI:10.2344/0003-3006-58.2.73 | 2011 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Christensen 2011 A double-blind placebo-controlled comparison of a novel formulation of intravenous diclofenac and ketorolac for postoperative third molar… PMID:21679043 | 2011 | this review only | not stated | not extracted yet |
| Cooper 2019 Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled,… DOI:10.1080/03007995.2019.1655257 | 2019 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Cooper 2019 Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled,… PMID:31402718 | 2019 | this review only | not stated | not extracted yet |
| Daniels 2001 A double-blind, randomized comparison of intramuscularly and intravenously administered parecoxib sodium versus ketorolac and placebo in a… DOI:10.1016/s0149-2918(01)80088-6 | 2001 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Daniels 2001 A double-blind, randomized comparison of intramuscularly and intravenously administered parecoxib sodium versus ketorolac and placebo in a… PMID:11519767 | 2001 | this review only | not stated | not extracted yet |
| Daniels 2006 Rofecoxib 50 mg and valdecoxib 20 or 40 mg in adults and adolescents with postoperative pain after third molar extraction: Results of two… DOI:10.1016/j.clinthera.2006.07.005 | 2006 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Daniels 2006 Rofecoxib 50 mg and valdecoxib 20 or 40 mg in adults and adolescents with postoperative pain after third molar extraction: results of two… PMID:16990080 | 2006 | this review only | not stated | not extracted yet |
| Daniels 2011 Evaluation of the Dose Range of Etoricoxib in an Acute Pain Setting Using the Postoperative Dental Pain Model DOI:10.1097/ajp.0b013e3181ed0639 | 2011 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Daniels 2011 Evaluation of the dose range of etoricoxib in an acute pain setting using the postoperative dental pain model. PMID:21188849 | 2011 | this review only | not stated | not extracted yet |
| Fricke 2002 Valdecoxib Is More Efficacious Than Rofecoxib in Relieving Pain Associated With Oral Surgery DOI:10.1097/00045391-200203000-00003 | 2002 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Fricke 2002 Valdecoxib is more efficacious than rofecoxib in relieving pain associated with oral surgery. PMID:11897923 | 2002 | this review only | not stated | not extracted yet |
| Gatoulis 2012 Assessment of the Efficacy and Safety Profiles of Aspirin and Acetaminophen With Codeine: Results From 2 Randomized, Controlled Trials in… DOI:10.1016/j.clinthera.2011.11.018 | 2012 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Gatoulis 2012 Assessment of the efficacy and safety profiles of aspirin and acetaminophen with codeine: results from 2 randomized, controlled trials in… PMID:22169050 | 2012 | this review only | not stated | not extracted yet |
| Hill 2006 Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and… DOI:10.1016/j.clinthera.2006.09.015 | 2006 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Hill 2006 Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and… PMID:17062301 | 2006 | this review only | not stated | not extracted yet |
| Kellstein 2020 Evaluation of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: A Pilot, Dose-Ranging,… DOI:10.1007/s40268-020-00310-7 | 2020 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Kellstein 2020 Evaluation of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: A Pilot, Dose-Ranging,… PMID:32506309 | 2020 | this review only | not stated | not extracted yet |
| Korn 2004 Comparison of rofecoxib and oxycodone plus acetaminophen in the treatment of acute pain: A randomized, double-blind, placebo-controlled… DOI:10.1016/s0149-2918(04)90076-8 | 2004 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Korn 2004 Comparison of rofecoxib and oxycodone plus acetaminophen in the treatment of acute pain: a randomized, double-blind, placebo-controlled… PMID:15220020 | 2004 | this review only | not stated | not extracted yet |
| Malmstrom 2004a Etoricoxib in acute pain associated with dental surgery: A randomized, double-blind, placebo- and active comparator-controlled… DOI:10.1016/s0149-2918(04)90067-7 | 2004 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Malmstrom 2004a Etoricoxib in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled… PMID:15220011 | 2004 | this review only | not stated | not extracted yet |
| Malmstrom 2004b A Randomized, Double-Blind, Parallel-Group Study Comparing the Analgesic Effect of Etoricoxib to Placebo, Naproxen Sodium, and… DOI:10.1097/00002508-200405000-00004 | 2004 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Malmstrom 2004b A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and… PMID:15100590 | 2004 | this review only | not stated | not extracted yet |
| Manvelian 2012 A Phase 2 Study Evaluating the Efficacy and Safety of a Novel, Proprietary, Nano-Formulated, Lower Dose Oral Diclofenac DOI:10.1111/j.1526-4637.2012.01479.x | 2012 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Manvelian 2012 A phase 2 study evaluating the efficacy and safety of a novel, proprietary, nano-formulated, lower dose oral diclofenac. PMID:23043637 | 2012 | this review only | not stated | not extracted yet |
| Mehlisch 2003 Single doses of parecoxib sodium intravenously are as effective as ketorolac in reducing pain after oral surgery DOI:10.1016/s0278-2391(03)00315-x | 2003 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Mehlisch 2003 Single doses of parecoxib sodium intravenously are as effective as ketorolac in reducing pain after oral surgery. PMID:12966478 | 2003 | this review only | not stated | not extracted yet |
| Mehlisch 2004 The analgesic efficacy of intramuscular parecoxib sodium in postoperative dental pain DOI:10.14219/jada.archive.2004.0085 | 2004 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Mehlisch 2004 The analgesic efficacy of intramuscular parecoxib sodium in postoperative dental pain. PMID:15622663 | 2004 | this review only | not stated | not extracted yet |
| Moberly 2007 A randomized, double-blind, celecoxib- and placebo-controlled study of the effectiveness of CS-706 in acute postoperative dental pain DOI:10.1016/s0149-2918(07)80078-6 | 2007 | this review only | not stated | not extracted yet |
| Moberly 2007 A randomized, double-blind, celecoxib- and placebo-controlled study of the effectiveness of CS-706 in acute postoperative dental pain. PMID:17577461 | 2007 | this review only | not stated | not extracted yet |
| Morrison 2000 THE OPTIMAL ANALGESIC DOSE OF ROFECOXIB: OVERVIEW OF SIX RANDOMIZED CONTROLLED TRIALS DOI:10.14219/jada.archive.2000.0119 | 2000 | this review only | not stated | not extracted yet |
| Morrison 2000 The optimal analgesic dose of rofecoxib: Overview of six randomized controlled trials. PMID:11143737 | 2000 | this review only | not stated | not extracted yet |
| Norholt 1995 A Randomized, Double‐Blind, Placebo‐Controlled, Dose‐Response Study of the Analgesic Effect of Lornoxicam After Surgical Removal of… DOI:10.1002/j.1552-4604.1995.tb05018.x | 1995 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Norholt 1995 A randomized, double-blind, placebo-controlled, dose-response study of the analgesic effect of lornoxicam after surgical removal of… PMID:7665721 | 1995 | this review only | not stated | not extracted yet |
| Rangaswamy 2016 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Schwartz 2007 MK-0703 (a Cyclooxygenase-2 inhibitor) in Acute Pain Associated with Dental Surgery: A Randomized, Double-Blind, Placebo- and Active… DOI:10.1097/mjt.0b013e31802dfb62 | 2007 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Schwartz 2007 MK-0703 (a cyclooxygenase-2 inhibitor) in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active… PMID:17303970 | 2007 | this review only | not stated | not extracted yet |
| Varner 2009 A Randomized, Controlled, Dose-ranging Study Investigating Single Doses of GW406381, Naproxen Sodium, or Placebo in Patients With Acute… DOI:10.1097/ajp.0b013e3181a085fa | 2009 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Varner 2009 A randomized, controlled, dose-ranging study investigating single doses of GW406381, naproxen sodium, or placebo in patients with acute… PMID:19692798 | 2009 | this review only | not stated | not extracted yet |
| Weiser 2018 Efficacy and safety of a fixed‐dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third… DOI:10.1002/ejp.1068 | 2017 | this review only | Alveolar osteitis (dry socket) occurrence | not extracted yet |
| Weiser 2018 Efficacy and safety of a fixed-dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third… PMID:28805281 | 2018 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
| Review | Shared studies | Jaccard |
|---|---|---|
| Analgesic Efficacy of Celecoxib Versus Ibuprofen After Third Molar Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled… (2026) | 2 | 0.03 |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients undergoing simple exodontia or third molar surgery | Patients after tooth extraction or third molar surgery (traditional NSAIDs n=2,888 in 19 trials; COX-2 inhibitors n=3,820 in 13 trials) |
| Intervention | Traditional NSAIDs and COX-2 selective inhibitors | Traditional NSAIDs: aspirin, diclofenac, ibuprofen, ketorolac, naproxen sodium; COX-2 inhibitors: celecoxib, etoricoxib, parecoxib, rofecoxib, valdecoxib |
| Comparison | Placebo or untreated control group | Placebo or untreated control |
| Outcomes | Alveolar osteitis (dry socket) frequency | Alveolar osteitis (OR, fixed-effect Mantel-Haenszel; absolute risk increase for rofecoxib) |
| Study designs | Clinical trials; trials with loss of more than 20% of patients excluded | 25 clinical trials (24 parallel design) |
| Timing | Not specified | Not specified |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | No | No | yes |
| 5Study selection in duplicate | No | No | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: No · NRSI: N/A | NRSI: N/A · RCT: No | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | No | No | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |