Table 2.
Host Modulation Therapeutic Agents in Patients with Periodontitis.
| Host Modulatory Agent | Type of Study | Follow-up | Clinical Outcomes | Subclinical Outcomes | Authors and Year |
|---|---|---|---|---|---|
| Statins | |||||
| RSV or ATV | RCT | 9 mo | Significantly higher PPD reduction for RSV gel (4.6 mm) and ATV gel (3.4 mm) than with placebo gel (1.9 mm) as adjuncts to SRP at 9-mo follow-up. Significantly higher CAL gain for RSV gel (4.3 mm) and ATV gel (3.3 mm) vs. placebo gel (1.9 mm) as adjuncts to SRP at 9-mo follow-up. Significantly higher intrabony defect depth reduction for RSV gel (4.3 mm) and ATV gel (3.3 mm) vs. placebo gel (0.1 mm). Significantly greater improvements in PPD reduction, CAL gain, and defect depth reduction with RSV gel than with ATV gel from baseline to 6 mo and from 6 to 9 mo. | Not investigated | Pradeep et al. (2016) |
| SMV | RCT | 6 mo | Significantly greater PPD reduction of 2.6 mm for SMV gel with SRP over placebo gel with SRP at 6 mo. Greater percentage of bone fill for SMV gel over placebo gel (34.01%) versus (2.62%). | Not investigated | Priyanka et al.2017) |
| RSV or ATV | RCT | 9 mo | Additional PPD reduction (1.2 mm) and additional gain in relative vertical CAL (0.6 mm), relative horizontal CAL (0.5 mm), and 7.6% additional defect depth reduction in the group with 1.2% RSV gel with SRP vs. group with 1.2% ATV with SRP. | Not investigated | Garg and Pradeep 2017) |
| SMV, RSV, ATV | Systematic review with meta-analysis | 3, 6, and 9 mo | Significant PPD reduction: weighted mean difference of 0.76 mm (at 3 mo) and 1.51 mm (at 6 mo) for local statins over placebo. Significant CAL gain: weighted mean difference of 1.17 mm (at 3 mo) and 1.84 mm (at 6 mo) for local statins over placebo. Significant residual radiographic depth reduction: weighted mean difference of 0.38 mm for OFD + PRF + local statins over OFD + PRF. | No significant decrease in IL-1α concentration in GCF and IL-6 expression in periodontal tissues for local statins combined with periodontal treatment. | Bertl et al. (2017) |
| SMV, RSV, ATV | Systematic review with meta-analysis | 6 and 9 mo | Significant PPD reduction: Mean difference of 1.83 mm (at 3 mo) and 2.25 mm (at 6 mo) for local statins over placebo combined with SRP in infrabony defects. | Not investigated | Donos et al. (2020) |
| Probiotics | |||||
| Lactobacillus brevis CD2 | RCT | 14 d | No significant changes in BOP in the probiotic group. Significant increase in BOP at days 10 and 14 vs. baseline in the placebo group. | Significant increase in nitric oxide levels in GCF only in the placebo group vs. baseline. | Lee et al. (2015) |
| Lactobacillus plantarum, L. brevis, and Pediococcus acidilactici | RCT | 6 wk | Significantly higher reduction in the number of sites with higher GI scores (GI = 3) in the probiotic group combined with mechanical plaque removal for treatment of gingivitis. | Significant reduction in Tannerella forsythia only in the probiotics group. | Montero et al. (2017) |
| Bifido-bacterium animalis subsp. lactis | RCT | 90 d | Significantly higher PPD reduction for moderate (0.3 mm) and deep (0.9 mm) pockets in the probiotics group over placebo group as adjuncts to SRP. Significantly higher CAL gain for moderate (0.5 mm) and deep (1.5 mm) pockets in the probiotics group over placebo group as adjuncts to SRP. | Significantly higher levels of IL-1β (at 30 and 90 d) and IL-8 (30 d) in the placebo group vs. the probiotics group as adjuncts to SRP. Significantly higher levels of IL-10 (at 30 d) in the probiotics group vs. baseline. | Invernici et al. (2018) |
| Lactobacillus reuteri | RCT | 24 wk | Additional reduction of 0.3 mm in PPD in the probiotics group vs. placebo as adjuncts to SRP. Significantly fewer sites in need for surgery in the probiotics group vs. placebo as adjuncts to SRP. | No significant differences on the levels of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans between groups | Laleman et al. (2020) |
| Probiotics (different strains) | Systematic review with meta-analysis | >6 mo | No significant benefit in PPD reduction (0.38 mm) for probiotics vs. placebo as adjuncts to SRP at 6 mo follow-up. | Not investigated | Donos et al. (2020) |
| Probiotics (different strains) | Systematic review with meta-analysis | >3 mo | Significant benefit for probiotics vs. placebo in CAL gain at 3 mo (0.18 mm), 6 mo (0.3 mm), and 9 mo (0.9 mm). Significant improvement in PPD reduction for probiotics vs. placebo at 3 mo (0.2 mm) and 12 mo (1.2 mm). | No significant changes in the reduction of P. gingivalis, T. forsythia, P. intermedia, and F. nucleatum associated with probiotics use. | Ho et al. (2020) |
| Bisphosphonates | |||||
| Alendronate | RCT | 6 mo | Additional PPD reduction of 2.3 mm, CAL gain of 2.4 mm, and vertical defect fill for 1% alendronate gel vs. placebo gel as adjuncts to SRP. | Not investigated | Sharma and Pradeep 2012) |
| Alendronate | RCT | 6 mo | Additional PPD reduction, CAL gain, and radiographic bone fill in intrabony defects for 1% alendronate gel vs. placebo gel as adjuncts to OFD. | Not investigated | Carvalho Dutra et al. (2019) |
| Alendronate | RCT | 9 mo | Additional PPD reduction of 0.8 mm, CAL gain of 1.0 mm, and 8% vertical defect fill in intrabony defects for 1% alendronate gel combined with OFD vs. PRF and OFD. Additional PPD reduction of 1.7 mm, CAL gain of 2.1 mm, and 47% vertical defect fill in intrabony defects for 1% alendronate gel vs. OFD alone. | Not investigated | Kanoriya et al. (2016) |
| Alendronate | RCT | 9 mo | Additional PPD reduction and CAL gain of 0.7 mm and 6% vertical defect fill in mandibular degree II furcation defects for 1% alendronate gel combined with OFD vs. PRF and OFD. Additional PPD reduction of 2.0 mm, CAL gain of 1.8 mm, and 45% vertical defect fill in intrabony defects for 1% alendronate gel vs. OFD alone. | Not investigated | Kanoriya et al. (2017) |
| Alendronate | RCT | 9 mo | Additional PPD reduction of 0.8 mm and 10% vertical defect fill in intrabony defects for 1% alendronate gel vs. 1.2% ATV gel as adjuncts to SRP. Additional PPD reduction of 2.8 mm, CAL gain of 2.0 mm, and 43% vertical defect fill in intrabony defects for 1% alendronate gel vs. placebo gel as adjuncts to SRP. | Not investigated | Pradeep et al. (2017) |
| Alendronate | Systematic review with meta-analysis | 6 to 9 mo | PPD reduction: mean difference of 2.15 ± 0.4 mm for alendronate gels and SRP in infrabony defects vs. SRP and placebo gels. | Not investigated | Donos et al. (2020) |
| n-3 PUFAs | |||||
| n-3 PUFAs and ASA | RCT | 6 mo | Additional PPD reduction of 0.6 mm and CAL gain of 0.7 mm for n-3 PUFAs and ASA vs. placebo capsules as adjuncts to SRP. | Significant reduction of salivary RANKL and MMP-8 for n-3 PUFAs and ASA vs. placebo capsules as adjuncts to SRP. | El-Sharkawy et al. (2010) |
| n-3 PUFAs and ASA | RCT | 6 mo | Additional PPD reduction of 0.7 mm and CAL gain of 0.4 mm for n-3 PUFAs and ASA vs. placebo capsules as adjuncts to OFD and DFDBA. | Significant reduction of IL-1β in GCF for n-3 PUFAs and ASA vs. placebo capsules as adjuncts to OFD and DFDBA. | Elkhouli (2011) |
| n-3 PUFAs and ASA | RCT | 3 mo | Additional PPD reduction of 0.17 mm and higher reduction in number of sites with PPD ≥5 mm for DHA and ASA vs. placebo capsules and ASA. | Significant reduction of CRP and IL-1β in GCF but not IL-6 for DHA and ASA vs. placebo capsules and ASA. | Naqvi et al. (2014) |
| n-3 PUFAs and ASA | RCT | 6 mo | No additional clinical benefit for PPD reduction and CAL gain for low-dose n-3 PUFAs vs. placebo capsules as adjuncts to SRP. | Significant reduction of salivary TNF-α for low dose n-3 PUFAs. | Keskiner et al. (2017) |
| n-3 PUFAs | RCT | 6 mo | Additional PPD reduction of 1.0 mm and CAL gain of 0.8 mm for n-3 PUFAs vs. placebo capsules as adjuncts to SRP in women who are postmenopausal with periodontitis. | Significantly higher superoxide dismutase activity in GCF for n-3 PUFA. | Elgendy and Kazem (2018) |
| n-3 PUFAs and ASA | RCT | 6 mo | Additional CAL gain of 0.5 mm for moderate and 1.0 mm for deep pockets for n-3 PUFAs and ASA after SRP vs. placebo capsules and SRP in diabetic patients. | Significant reduction in hemoglobin A1c for n-3 PUFAs and ASA after SRP in diabetic patients. | Castro Dos Santos et al. (2020) |
ASA, aspirin; ATV, atorvastatin; BOP, bleeding on probing; CAL, clinical attachment level; DFDBA, demineralized freeze-dried bone allograft; DHA, docosahexaenoic acid; GCF, gingival crevicular fluid; GI, gingival index; IL, interleukin; MMP-8, metalloproteinase 8; n-3, omega-3; OFD, open flap debridement; PPD, probing pocket depth; PRF, platelet-rich fibrin; PUFA, polyunsaturated fatty acid; RCT, randomized controlled trial; RSV, rosuvastatin; SMV, simvastatin; SRP, scaling and root planing.