Sclerostin-Neutralizing Antibody Enhances Bone Regeneration Around Oral Implants

Yu, Shan Huey; Hao, Jie; Fretwurst, Tobias; Liu, Min; Kostenuik, Paul J.; Giannobile, William V.; Jin, Qiming

doi:10.1089/ten.tea.2018.0013

Cited by 30 publications

(37 citation statements)

References 41 publications

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“…The findings from this investigation demonstrate that systemically-administered Scl-Ab was associated with improved osseous repair of large alveolar bone defects in comparison with the effects of local Scl-Ab formulated in PLGA microspheres, microspheres alone, or no treatment. These findings build on the large body of evidence demonstrating that systemic Scl-Ab therapy stimulates new bone formation and increased alveolar bone volume and density following experimental periodontitis and around large bone defects at the time of dental implant placement 21,23,31 . These results suggest therapeutic potential for this approach in a variety of dental applications.…”

Section: Discussionmentioning

confidence: 53%

“…Considering the unique characteristics of Scl-Ab for the promotion of bone density in a variety of contexts, several studies have reported the ability of Scl-Ab to address unmet dental needs. Scl-Ab administration has previously shown inhibition of periodontal disease progression 32 , enhancement of the recovery from periodontal disease 21 , and increased osteointegration and bone regeneration around dental implants 23 . Moreover, in two large clinical studies, a single case of osteonecrosis of the jaw (ONJ) bone was reported 17,18,31,32 whereas antiresorptive agents including bisphosphonates and denosumab are associated with an increased risk of ONJ.…”

Section: Discussionmentioning

confidence: 99%

“…Scl-Ab administration led to enhanced bone formation in a critical-sized femoral defect model in rats 20 , and Scl-Ab administration also increased bone volume, bone mineral density, and alveolar bone height after experimental periodontitis 21 . Moreover, Scl-Ab reversed alveolar bone loss in a rat model of chronic edentulism 22 and Scl-Ab also improved mechanical fixation of oral implants by enhancing regeneration of the supporting bone 23 . Such results indicate that Scl-Ab may have utility as a bone anabolic agent for treating large alveolar bone defects by increasing bone volume and improving bone quality.…”

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confidence: 92%

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Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects

Yao

Kauffmann

Maekawa

et al. 2020

Sci Rep

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Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

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Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects

Yao

Kauffmann

Maekawa

et al. 2020

Sci Rep

Self Cite

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“…[ 67 , 68 ] In addition, Scl-Ab administration can enhance osseointegration and bone regeneration around bone implant and dental implants, which indicates a potential therapeutic approach to reduce the healing time and accelerate bone regeneration after implant placement. [ 69 , 70 ] Moreover, an animal experiment in 2018 proved that treatment with Scl-Ab significantly increased mandibular bone mass and alveolar height in wild-type mice. [ 63 ] Use of Scl-Ab is a prospective treatment method for bone absorption induced by periodontitis and other oral therapies like orthodontic or implant treatment.…”

Section: Anti-sclerostin Antibodiesmentioning

confidence: 99%

Sclerostin regulation: a promising therapy for periodontitis by modulating alveolar bone

Wang²,

Li³

et al. 2020

Chinese Medical Journal

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Periodontitis is one of the most prevalent epidemics affecting human health and life recently, and exploration of the pathogenesis and treatment of periodontitis has been valued by scholars. In recent years, sclerostin, a new factor on bone resorption and reconstruction caused by inflammation and mechanical stimulation, has been a research hotspot. This article summarizes the researches on sclerostin in periodontitis development in recent years. Among them, sclerostin has been shown to be a critical negative regulator of bone formation, thereby inhibiting bone remodeling in periodontitis development, and is closely associated with tooth movement. Besides, evidence indicates that the removal of sclerostin seems to reasonably protect the alveolar bone from resorption. Regulation of sclerostin expression is a novel, promising treatment for periodontitis and addresses several complications seen with traditional therapies; accordingly, many drugs with similar mechanisms have emerged. Moreover, the application prospect of sclerostin in periodontal therapy combined with orthodontic treatment is another promising approach. There are also a lot of drugs that regulate sclerostin. Anti-sclerostin antibody (Scl-Ab) is the most direct one that inhibits bone resorption caused by sclerostin. At present, drugs that inhibit the expression of sclerostin have been applied to the treatment of diseases such as multiple myeloma and osteoporosis. Therefore, the application of sclerostin in the oral field is just around the corner, which provides a new therapeutic bone regulation strategy in oral and general health.

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“…This research needs to be guided by an appropriate understanding of the cell biological mechanisms underlying pathological changes and regeneration in the oral tissue, including the periodontium and the dental tissue. Due to the major role of Wnt signaling and the respective regulators in development and healing, research in regenerative medicine and dentistry has evaluated the feasibility of targeting the pathway for therapeutic approaches ( Florio et al ., 2016; Heiland et al ., 2010; Taut et al ., 2013; Yu et al ., 2018).…”

Section: Introductionmentioning

confidence: 99%

The role of sclerostin and dickkopf-1 in oral tissues – A review from the perspective of the dental disciplines

et al. 2019

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Wnt signaling is of high relevance in the development, homeostasis, and regeneration of oral tissues. Therefore, Wnt signaling is considered to be a potential target for therapeutic strategies. The action of Wnt is tightly controlled by the inhibitors sclerostin (SOST) and Dickkopf (DKK)-1. Given the impact of SOST and DKK-1 in hard tissue formation, related diseases and healing, it is of high relevance to understand their role in oral tissues. The clinical relevance of this knowledge is further underlined by systemic and local approaches which are currently in development for treating a variety of diseases such as osteoporosis and inflammatory hard tissue resorption. In this narrative review, we summarize the current knowledge and understanding on the Wnt signaling inhibitors SOST and DKK-1, and their role in physiology, pathology, and regeneration in oral tissues. We present this role from the perspective of the different specialties in dentistry, including endodontics, orthodontics, periodontics, and oral surgery.

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Sclerostin-Neutralizing Antibody Enhances Bone Regeneration Around Oral Implants

Cited by 30 publications

References 41 publications

Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects

Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects

Sclerostin regulation: a promising therapy for periodontitis by modulating alveolar bone

The role of sclerostin and dickkopf-1 in oral tissues – A review from the perspective of the dental disciplines

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