Non-Cochrane · intervention · PM42046838
Adjunctive Use of Locally Delivered Statins in Periodontal Therapy and Pre-Implant Bone Regeneration: A Systematic Review and Meta-Analysis.
Yoshida Koki, Heller Sofia, Mousa Nur, et al. · Clinical and experimental dental research · 2026 · PubMed · doi:10.1002/cre2.70364
Findings
8 findings
| Population | ||||
|---|---|---|---|---|
| Adults with periodontitis (pockets 5 mm or deeper, intrabony or furcation defects) undergoing Step 2 non-surgical periodontal therapy | SRP plus locally delivered 1.2% atorvastatin gel | SRP alone (placebo gel or no gel) | Clinical attachment level (CAL), change from baseline (mm) 6 months · Periodontal clinics (Step 2 NSPT) | MD 1.70 [1.22, 2.19] GRADE not reported 6 studies · 332 participants |
| Adults with periodontitis (pockets 5 mm or deeper, intrabony or furcation defects) undergoing Step 2 non-surgical periodontal therapy | SRP plus locally delivered 1.2% atorvastatin gel | SRP alone (placebo gel or no gel) | Probing pocket depth (PPD), change from baseline (mm) 6 months · Periodontal clinics (Step 2 NSPT) | MD 1.39 [0.99, 1.79] GRADE not reported 6 studies · 332 participants |
| Adults with periodontitis (pockets 5 mm or deeper, intrabony or furcation defects) undergoing Step 2 non-surgical periodontal therapy | SRP plus locally delivered 1.2% rosuvastatin gel | SRP alone (placebo gel or no gel) | Probing pocket depth (PPD), change from baseline (mm) 6 months · Periodontal clinics (Step 2 NSPT) | MD 1.91 [1.35, 2.48] GRADE not reported 4 studies · 211 participants |
| Adults with periodontitis (pockets 5 mm or deeper, intrabony or furcation defects) undergoing Step 2 non-surgical periodontal therapy | SRP plus locally delivered 1.2% rosuvastatin gel | SRP alone (placebo gel or no gel) | Clinical attachment level (CAL), change from baseline (mm) 6 months · Periodontal clinics (Step 2 NSPT) | MD 1.94 [1.33, 2.56] GRADE not reported 4 studies · 211 participants |
| Adults with periodontitis (pockets 5 mm or deeper, intrabony or furcation defects) undergoing Step 2 non-surgical periodontal therapy | SRP plus locally delivered 1.2% simvastatin gel | SRP alone (placebo gel or no gel) | Clinical attachment level (CAL), change from baseline (mm) 6 months · Periodontal clinics (Step 2 NSPT) | MD 2.17 [1.68, 2.66] GRADE not reported 4 studies · 228 participants |
| Adults with periodontitis (pockets 5 mm or deeper, intrabony or furcation defects) undergoing Step 2 non-surgical periodontal therapy | SRP plus locally delivered 1.2% simvastatin gel | SRP alone (placebo gel or no gel) | Probing pocket depth (PPD), change from baseline (mm) 6 months · Periodontal clinics (Step 2 NSPT) | MD 2.34 [1.65, 3.03] GRADE not reported 4 studies · 228 participants |
| Adults with periodontitis and intrabony or Class II furcation defects undergoing Step 3 periodontal surgery | Open flap debridement with PRF (and HA in furcation) plus locally delivered statin gel (atorvastatin or rosuvastatin) | Same surgical procedure without statin | Clinical attachment level (CAL), change from baseline (mm) 9 months · Periodontal surgery (Step 3) | MD 0.69 [0.42, 0.96] GRADE not reported 3 studies · 190 participants |
| Adults with periodontitis and intrabony or Class II furcation defects undergoing Step 3 periodontal surgery | Open flap debridement with PRF (and HA in furcation) plus locally delivered statin gel (atorvastatin or rosuvastatin) | Same surgical procedure without statin | Probing pocket depth (PPD), change from baseline (mm) 9 months · Periodontal surgery (Step 3) | MD 0.80 [0.56, 1.05] GRADE not reported 3 studies · 190 participants |
Included primary studies 21
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Martande 2016 Platelet-Rich Fibrin Combined With 1.2% Atorvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled… PMID:27294433 | 2016 | 3 other reviews | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2016b Platelet-Rich Fibrin With 1.2% Rosuvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical… PMID:27452270 | 2016 | 2 other reviews | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Garg 2017 1.2% Rosuvastatin and 1.2% Atorvastatin Gel Local Drug Delivery and Redelivery in the Treatment of Class II Furcation Defects: A… PMID:27715376 | 2017 | 1 other review | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Issa 2020 Guided tissue regeneration of intrabony defects with perforated barrier membranes, simvastatin, and EDTA root surface modification: A… PMID:31448832 | 2020 | 1 other review | not stated | not extracted yet |
| Pankaj 2018 Comparative evaluation of subgingivally delivered 1.2% rosuvastatin and 1% metformin gel in treatment of intrabony defects in chronic… PMID:29802627 | 2018 | 1 other review | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2016a 1.2% Rosuvastatin Versus 1.2% Atorvastatin Gel Local Drug Delivery and Redelivery in Treatment of Intrabony Defects in Chronic… PMID:26878748 | 2016 | 1 other review | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2017 Comparative evaluation of subgingivally delivered 1% alendronate versus 1.2% atorvastatin gel in treatment of chronic periodontitis: a… PMID:27091596 | 2017 | 1 other review | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Christiansen 2023 Local simvastatin and inflammation during periodontal mini-flap wound healing: Exploratory results. PMID:36017934 | 2023 | this review only | not stated | not extracted yet |
| Cruz 2021 Clinical efficacy of simvastatin gel combined with polypropylene membrane on the healing of extraction sockets: A triple-blind, randomized… PMID:33715258 | 2021 | this review only | not stated | not extracted yet |
| Gunjiganur Vemanaradhya 2017 Effect of 1.2% of simvastatin gel as a local drug delivery system on Gingival Crevicular Fluid interleukin-6 & interleukin-8 levels in non… PMID:28601733 | 2017 | this review only | not stated | not extracted yet |
| Killeen 2022 Effect of locally applied simvastatin on clinical attachment level and alveolar bone in periodontal maintenance patients: A randomized… PMID:35622060 | 2022 | this review only | not stated | not extracted yet |
| Kumari 2016 Efficacy of Subgingivally Delivered 1.2% Atorvastatin in the Treatment of Chronic Periodontitis in Patients With Type 2 Diabetes Mellitus:… PMID:27442085 | 2016 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Kumari 2017 Subgingivally delivered 1.2% atorvastatin in the treatment of chronic periodontitis among smokers: a randomized, controlled clinical trial. PMID:26988864 | 2017 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2010 Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial. PMID:20151799 | 2010 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2012 Clinical efficacy of subgingivally delivered 1.2-mg simvastatin in the treatment of individuals with Class II furcation defects: a… PMID:22348696 | 2012 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2013 (atorvastatin) Clinical efficacy of subgingivally delivered 1.2% atorvastatin in chronic periodontitis: a randomized controlled clinical trial. PMID:23030241 | 2013 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2013 (simvastatin) Efficacy of subgingivally delivered simvastatin in the treatment of patients with type 2 diabetes and chronic periodontitis: a randomized… PMID:22420871 | 2013 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2015 Efficacy of locally delivered 1.2% rosuvastatin gel to non-surgical treatment of patients with chronic periodontitis: a randomized,… PMID:25786565 | 2015 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Pradeep 2016 (furcation) Rosuvastatin 1.2 mg In Situ Gel Combined With 1:1 Mixture of Autologous Platelet-Rich Fibrin and Porous Hydroxyapatite Bone Graft in… PMID:26439386 | 2016 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Rao 2013 Simvastatin local drug delivery in smokers with chronic periodontitis: a randomized controlled clinical trial. PMID:23713634 | 2013 | this review only | Probing pocket depth (PPD), change from baseline (mm); Clinical attachment level (CAL), change from baseline (mm) | not extracted yet |
| Yaghobee 2020 Effect of Simvastatin on Bone Regeneration: A Histologic and Histomorphometric Analysis. PMID:32084353 | 2020 | 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 question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults undergoing Step 2 subgingival instrumentation/NSPT, Step 3 periodontal surgery, Step 4 supportive periodontal care, or pre-implant bone regeneration procedures | Adults with periodontitis: 13 Step 2 trials (n=38-104), 6 Step 3 trials (n=40-110; 2 maintenance Step 4), 2 pre-implant trials (n=24-33) |
| Intervention | Local application of statins as an adjunct | Local atorvastatin, rosuvastatin or simvastatin gel (mostly 1.2% methylcellulose); simvastatin in pre-implant trials |
| Comparison | Identical procedures with or without adjunctive statins | SRP + placebo gel; surgery with or without PRF/HA; bovine bone mineral without statin |
| Outcomes | PPD, CAL, BoP, gingival index, plaque index; radiographic bone outcomes | PPD and CAL pooled (6 months: ATV n=6, RSV n=4, SIM n=4 studies; 9 months surgical n=3); BoP, GI, PI, radiographic and ridge outcomes narrative |
| Study designs | RCTs | 21 RCTs (15 in meta-analysis) |
| Timing | 6 months for Step 2 and 9 months for Step 3 meta-analysis; other follow-ups narrative | 6-month (Step 2) and 9-month (Step 3) pooling; follow-up 1.5 to 12 months overall |
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 | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | Yes | Yes | 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: Yes · NRSI: N/A | NRSI: N/A · RCT: Partial Yes | 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 | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Low | Low | yes |