Non-Cochrane · intervention · PM41356111
Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta-analysis of animal models.
Yang Miaomiao, Ma Yongqing, Qu Xiaofu, et al. · Experimental and therapeutic medicine · 2026 · PubMed · doi:10.3892/etm.2025.13026
Findings
Population Animal models (rats and mice) of experimental periodontal disease
26 findings
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Sex: female | SMD -3.75 [-7.64, 0.15] GRADE not reported 2 studies · 60 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Bone volume fraction (BVF) Most commonly reported time point across studies | SMD 2.7 [0.69, 4.71] Low Downgraded: risk of bias, inconsistency 3 studies · 50 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Dose: 25 mg/kg | SMD -2.63 [-4.34, -0.91] GRADE not reported 3 studies · 52 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | TRAP5b (histology, osteoclast number) Most commonly reported time point across studies | SMD -0.21 [-2.24, 1.83] Low Downgraded: risk of bias, imprecision, inconsistency 2 studies · 54 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies | SMD -2.68 [-3.76, -1.59] Moderate Downgraded: risk of bias, inconsistency 8 studies · 182 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Serum osteocalcin (OCN) Most commonly reported time point across studies | SMD 2.64 [0.76, 4.51] Low Downgraded: risk of bias, imprecision, inconsistency 2 studies · 36 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Dose analysis, all studies with dose data | SMD -3.55 [-5.69, -1.4] Moderate Downgraded: risk of bias, inconsistency 4 studies · 92 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Species: rats | SMD -2.64 [-3.92, -1.37] GRADE not reported 5 studies · 132 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Route analysis, all studies with route data | SMD -3.27 [-4.52, -2.02] Moderate Downgraded: risk of bias, inconsistency 7 studies · 142 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | SOST-positive cells Most commonly reported time point across studies | SMD -6.06 [-10.29, -1.84] Moderate Downgraded: risk of bias, imprecision, inconsistency 3 studies · 70 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Direct vs indirect inhibition: direct inhibition | SMD -2.92 [-4.76, -1.07] GRADE not reported 5 studies · 112 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Ligature retention (as labeled in Figure S3) | MD -0.23 [-0.36, -0.1] GRADE not reported 5 studies · 112 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Dose: 5 mg/kg | SMD -5.77 [-7.24, -4.3] GRADE not reported 1 study · 40 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Serum P1NP Most commonly reported time point across studies | SMD 5.6 [-6.13, 17.32] Low Downgraded: risk of bias, imprecision, inconsistency 2 studies · 56 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Tissue mineral density (TMD/BMD) Most commonly reported time point across studies | SMD 2.51 [1.58, 3.44] Low Downgraded: risk of bias, inconsistency 2 studies · 36 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Induction method: gene knockout | SMD -4.15 [-6.49, -1.81] GRADE not reported 2 studies · 30 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Direct vs indirect inhibition: indirect inhibition | SMD -2.38 [-3.57, -1.2] GRADE not reported 3 studies · 70 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Ligature removed (as labeled in Figure S3) | MD -0.27 [-0.3, -0.24] GRADE not reported 1 study · 40 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Species: mice | SMD -2.9 [-5.64, -0.17] GRADE not reported 3 studies · 50 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Ligature removal vs retention analysis, all studies | MD -0.24 [-0.33, -0.14] GRADE not reported 6 studies · 152 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Sex analysis, all studies reporting sex | SMD -2.41 [-3.48, -1.34] Moderate Downgraded: risk of bias, inconsistency 7 studies · 166 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Induction method: ligature | SMD -2.33 [-3.49, -1.17] GRADE not reported 6 studies · 152 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Serum TRAP5b Most commonly reported time point across studies | SMD -7.9 [-22.08, 6.28] GRADE not reported 2 studies · 36 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Route: subcutaneous injection | SMD -1.97 [-2.71, -1.24] GRADE not reported 3 studies · 50 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Route: intraperitoneal injection | SMD -4.26 [-6.31, -2.2] GRADE not reported 4 studies · 92 participants |
| Inhibition of sclerostin activity (anti-sclerostin antibody, SOST gene knockout, or sclerostin-inhibiting agents) | Experimental periodontitis without sclerostin inhibition (vehicle, PBS or no treatment) | Alveolar bone loss (CEJ-ABC distance) Most commonly reported time point across studies · Sex: male | SMD -1.88 [-2.75, -1.02] GRADE not reported 5 studies · 106 participants |
Included primary studies 8
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Chen 2015 Sclerostin antibody treatment causes greater alveolar crest height and bone mass in an ovariectomized rat model of localized periodontitis. PMID:25868799 | 2015 | this review only | not stated | not extracted yet |
| Hadaya 2019 Clinically Relevant Doses of Sclerostin Antibody Do Not Induce Osteonecrosis of the Jaw (ONJ) in Rats with Experimental Periodontitis. PMID:30184271 | 2019 | this review only | not stated | not extracted yet |
| Kim 2017 Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. PMID:29240821 | 2017 | this review only | not stated | not extracted yet |
| Ozaki 2017 Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and… PMID:28937990 | 2017 | this review only | not stated | not extracted yet |
| Ren 2015 Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model. PMID:25757567 | 2015 | this review only | not stated | not extracted yet |
| Taut 2013 Sclerostin antibody stimulates bone regeneration after experimental periodontitis. PMID:23712325 | 2013 | this review only | not stated | not extracted yet |
| Yang 2016 Effect of sclerostin removal in vivo on experimental periodontitis in mice. PMID:27349550 | 2016 | this review only | not stated | not extracted yet |
| Yigit 2022 Effects of low dose doxycycline and caffeic acid phenethyl ester on sclerostin and bone morphogenic protein-2 expressions in experimental… PMID:35135409 | 2022 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Animal models of experimental periodontal disease | Rats and mice with experimental periodontitis (n=183 animals; 119 male, 64 female) |
| Intervention | Inhibition or neutralization of sclerostin activity | Sclerostin antibody (5 studies), SOST knockout (2), CAPE, low-dose doxycycline, infliximab, WP9QY |
| Comparison | Animal models with periodontal disease without sclerostin inhibition | Vehicle, PBS or no treatment |
| Outcomes | Alveolar bone loss; bone volume fraction, bone mineral density, bone-specific serum markers, number of SOST-positive cells | Alveolar bone loss (n=8 studies); BVF (n=3); TMD (n=2); P1NP (n=2); OCN (n=2); serum TRAP5b (n=2); histological TRAP5b (n=2); SOST-positive cells (n=3) |
| Study designs | In vivo randomized controlled trials | Randomized animal studies (n=8) |
| Timing | Most commonly reported time point across studies (e.g., 3 or 6 weeks) | Treatment from 5 days to 22 weeks |
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 | No | No | yes |
| 8Included studies described in detail | Yes | Partial Yes | no |
| 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: 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 | Critically Low | Critically Low | yes |