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Article Open Access

Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models

  • Authors:
    • Miaomiao Yang
    • Yongqing Ma
    • Xiaofu Qu
    • Zhe Qu
    • Jiang Sun
  • View Affiliations / Copyright

    Affiliations: Department of Implantation, Stomatological Hospital of Dalian University (Dalian Stomatological Hospital), Dalian, Liaoning 116021, P.R. China, Department of Oral Surgery, Stomatological Hospital of Dalian University (Dalian Stomatological Hospital), Dalian, Liaoning 116021, P.R China, VIP Clinic, Stomatological Hospital of Dalian University (Dalian Stomatological Hospital), Dalian, Liaoning 116021, P.R. China, Department of Periodontology, Stomatological Hospital of Dalian University (Dalian Stomatological Hospital), Dalian, Liaoning 116021, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 31
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    Published online on: November 25, 2025
       https://doi.org/10.3892/etm.2025.13026
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Abstract

Sclerostin, an osteocyte‑derived inhibitor of the Wnt/β‑catenin pathway, plays a key role in suppressing bone formation. To evaluate the therapeutic efficacy of sclerostin inhibition in mitigating alveolar bone loss and promoting regeneration in animal models of periodontal disease, the present meta‑analysis conducted a systematic search of PubMed, Embase, the Cochrane Library and Web of Science for studies published from inception to January 2025, without language restrictions. Eligible studies encompassed in vivo experiments investigating pharmacological or genetic strategies targeting sclerostin. A total of eight studies fulfilled the inclusion criteria and pooled analyses demonstrated a notable decrease in the distance between the cementoenamel junction and alveolar bone crest following sclerostin inhibition. Secondary outcomes indicated improvements in bone volume fraction and mineral density and serum osteocalcin levels, with a marked reduction in the number of sclerostin‑positive cells. Sclerostin inhibition effectively preserved alveolar bone and enhanced bone quality and metabolic activity in experimental periodontal disease. These findings highlight the potential of sclerostin as an adjunctive strategy for periodontal regeneration.
View Figures

Figure 1

Forest plot of alveolar bone loss.
Scl, sclerostin; df, degrees of freedom; LDD, low-dose doxycycline;
CAPE, caffeic acid phenethyl ester; IV, inverse variance model.

Figure 2

Subgroup analysis of alveolar bone
loss. (A) Direct versus indirect inhibition. (B) Dose. (C) Species.
(D) Sex. (E) Route of administration. (F) Induction method
(ligature and gene-knockout). ABL, alveolar bone loss; Scl,
sclerostin; df, degrees of freedom; LDD, low-dose doxycycline;
CAPE, caffeic acid phenethyl ester; SMD, standardized mean
difference; IV, inverse variance model.

Figure 3

Forest plots of BVF and TMD. (A) Bone
volume fraction. (B) Tissue mineral density. Scl, sclerostin; df,
degrees of freedom; SMD, standardized mean difference; IV, inverse
variance model; BVF, bone volume fraction; TMD, tissue mineral
density.

Figure 4

Forest plots of bone-specific
biomarkers and SOST-positive cells. (A) Bone-specific serum
biomarkers (P1NP, OCN and TRAP5b). (B) Histological test for
TRAP5b. (C) SOST-positive cells. Scl, sclerostin; df, degrees of
freedom; LDD, low-dose doxycycline; CAPE, caffeic acid phenethyl
ester; SMD, standardized mean difference; TRAP5b,
tartrate-resistant acid phosphatase 5b; SOST, sclerostin; IV,
Inverse Variance Model; Pp1NP, procollagen type I N-terminal
propeptide; OCN, osteocalcin; TRAP5b, tartrate-resistant acid
phosphatase 5b. Supplementary figure legends
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Copy and paste a formatted citation
Spandidos Publications style
Yang M, Ma Y, Qu X, Qu Z and Sun J: Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models. Exp Ther Med 31: 31, 2026.
APA
Yang, M., Ma, Y., Qu, X., Qu, Z., & Sun, J. (2026). Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models. Experimental and Therapeutic Medicine, 31, 31. https://doi.org/10.3892/etm.2025.13026
MLA
Yang, M., Ma, Y., Qu, X., Qu, Z., Sun, J."Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models". Experimental and Therapeutic Medicine 31.2 (2026): 31.
Chicago
Yang, M., Ma, Y., Qu, X., Qu, Z., Sun, J."Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models". Experimental and Therapeutic Medicine 31, no. 2 (2026): 31. https://doi.org/10.3892/etm.2025.13026
Copy and paste a formatted citation
x
Spandidos Publications style
Yang M, Ma Y, Qu X, Qu Z and Sun J: Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models. Exp Ther Med 31: 31, 2026.
APA
Yang, M., Ma, Y., Qu, X., Qu, Z., & Sun, J. (2026). Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models. Experimental and Therapeutic Medicine, 31, 31. https://doi.org/10.3892/etm.2025.13026
MLA
Yang, M., Ma, Y., Qu, X., Qu, Z., Sun, J."Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models". Experimental and Therapeutic Medicine 31.2 (2026): 31.
Chicago
Yang, M., Ma, Y., Qu, X., Qu, Z., Sun, J."Inhibition of sclerostin activity promotes bone regeneration in experimental periodontal disease: A systematic review and meta‑analysis of animal models". Experimental and Therapeutic Medicine 31, no. 2 (2026): 31. https://doi.org/10.3892/etm.2025.13026
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