|Year : 2012 | Volume
| Issue : 4 | Page : 133-137
Icariin: Can an herbal extract enhance dental implant outcomes?
Qiang Wang1, Xiaoying Wang2, Xin Xu2
1 Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, Shandong; Department of Prosthodontics, Jinan Stomatological Hospital, Jinan, PR China
2 Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, Shandong, PR China
|Date of Web Publication||5-Feb-2013|
Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, 44-1 Wenhuaxi Road, 250012 Jinan, Shandong
Source of Support: This work was supported by the National Natural Science Foundation of China (grant No.30901673), Conflict of Interest: None
Introduction: The success rate of dental implant is closely related to three aspects including supporting bone before implantation, osseointegration process, and prevention of peri-implantitis after implantation. Icariin is one of the traditional Chinese herbal medicines to treat impotence, improve sexual function, and enhance immune function. Recently, there are abundant evidences showing that icariin can strengthen bones, enhance bone healing, inhibit osteopenia, and inhibit inflammation. The Hypothesis: We hypothesize that Icariin may be applied clinically to strengthen and accelerate osseointegration of dental implants, inhibit the peri-implantitis, and shorten the rehabilitation time. Evaluation of the Hypothesis: Limited success has been achieved to help implant surgery in spite of much effort. The application of icariin might be a potential method to improve the success rate of dental implant, contributing greatly to implant dentistry.
Keywords: Dental implant, icariin, osseointegration
|How to cite this article:|
Wang Q, Wang X, Xu X. Icariin: Can an herbal extract enhance dental implant outcomes?. Dent Hypotheses 2012;3:133-7
| Introduction|| |
Dental implant is an established alternative for replacing missing teeth. It is regarded as a good option to restore the normal function, speech, health, and esthetics of patients regardless of injury, disease, or atrophy of the stomatognathic system.  Dental implants are more comfortable and efficient compared with traditional restorative materials such as fixed and removable dentures. An increasing number of patients with tooth loss tend to choose dental implants, but they do complain about the long treatment period, which lasts 6 months or so, longer than that involving traditional procedures. Dentists also face many challenges, such as inadequate alveolar bone volume before dental implant surgery. Besides, research has also shown that peri-implantitis is one of the main causes of dental implant failure. To date, no ideal treatment method has been reported to solve these problems.
An adequate volume of bone surrounding a dental implant is essential for the success of surgery. , Under normal circumstances, tooth loss due to different reasons may lead to alveolar resorption, such as tooth extraction, trauma, and periodontal disease. In addition, shortage of bone can hinder proper positioning of a dental implant according to prosthetic needs and treatment planning, unless the volume of hard and soft tissues is increased before implantation. On the contrary, it is essential not only to achieve well-anchored implants but also to obtain natural-looking esthetic results. Various procedures to reconstruct lost tissue, such as autogenous bone graft and allogeneic bone graft,  are available, and one current intriguing strategy is to apply a substance that could ultimately be confirmed as an agent of choice for the clinical promotion of bone healing and regeneration to the bone grafts (e.g., bone morphogenetic protein [BMP] and other biological molecules). , However, the clinical application thereof remains a challenge.
Wide bone-to-implant direct contact is crucial for the long-term clinical success of endosseous dental implant surgery. This condition is called osseointegration. The classic dental implant treatment requires a long healing period, which usually varies from 3 months to more than 6 months. During this period, bone regeneration and healing between the implant and bone occur, as does osseointegration. Many studies have focused on how to shorten the healing time and speed up the process of osseointegration. This process may be accelerated by altering the implant's surface roughness, by developing a biomimetic interface, or via local delivery of growth-promoting factors. ,,,, There is an ongoing effort in the research community to contribute to the osseointegration process.
Peri-implantitis is an inflammatory reaction of the tissues around an osseointegrated dental implant that results in loss of the supporting bone. It has an incidence rate of approximately 5-8%, which limits the clinical success of the surgery. Its common causes include unhealthy prosthesis, bacterial infection, smoking, and occlusion interference, among others. Peri-implantitis could be affected by the periodontal status of neighboring teeth, bone quality, surgical technique, and general health of the patient. Current methods for preventing and treating peri-implantitis include mechanical, chemical, electrochemical, or thermal decontamination, or any combination of these methods so that the surfaces can be further modified or altered in a favorable fashion to accommodate, facilitate, or promote more biofunctionality and bioactivity. , At present, much of the information on the effectiveness of these interventions is obtained from case reports such that no evidence-based consensus has been reached as to which option is clinically most advantageous. More strategies to prevent and treat peri-implantitis should be developed.
Icariin is the main effective constituent of epimedium, which is one of the most frequently used Chinese herbal medicines to treat impotence, improve sexual function, and enhance immune function. , It has been demonstrated to act as a phosphodiesterase 5 (PDE5) inhibitor, enhance the production of bioactive nitric oxide, and mimic the effects of testosterone. It has also exhibited antioxidant, antidepressant, and nootropic effects in animal studies, as well as for several other indications. Pharmacologic studies have shown that icariin is a flavonol, a type of flavonoid.
Recent studies have shown that icariin could promote bone formation and regeneration effectively and exerts its anti-osteoporotic effects by activating osteoblast activities and inhibiting osteoclast activities. ,,,, Icariin has been reported to be a strong candidate as an osteogenic compound for use in bone tissue engineering.  In spite of these findings, the precise mechanism of icariin remains unclear. Some studies found that icariin has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblasts in vitro, which may be mediated by increasing the production of bone morphogenetic proteins 2 (BMP-2) in osteoblasts.  Other studies have demonstrated that icariin exerts its potential osteogenic effects by inducing Runx2 expression, producing BMP-4, and activating BMP signaling. , Hsieh et al, reported that icariin inhibits osteoclast differentiation and bone resorption via the suppression of Mitogen-activated protein kinase/NF-kappa B (MAPK/NF-kB)-regulated hypoxia-inducible factor-1a (HIF-1a) and PGE2 synthesis.  In addition, icariin is regarded as a safe and effective natural anti-inflammatory drug. Chen  demonstrated that an icariin derivative can inhibit inflammation through the suppression of p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways.
| The Hypothesis|| |
Chinese herbal medicine has numerous advantages that an increasing number of researchers have expressed interest in it. It is relatively safe and cheap, making it worthwhile to explore and characterize its further uses. As icariin possesses intriguing activities associated with the success rate of dental implant surgery, promoting osteoblast activities, inhibiting osteoclast activities, and inhibiting inflammation, ,,,,,,,,,,,, it is reasonable to hypothesize that icariin can positively affect dental implant surgery including contributing to bone formation before implant surgery, promoting osseointegration, and preventing peri-implantitis.
BMPs are well known to be effective biological molecules that stimulate bone formation, and they are widely used for bone tissue engineering. Recent studies have shown that recombinant human BMP-2 absorbed into bovine type-1 collagen sponges consistently stimulates bone formation effectively at graft sites. However, the application of BMPs is relatively expensive, and these molecules are easily degraded when applied alone.  Abundant evidences have shown that icariin could amplify their function by activating BMP signaling systems, such as BMP-2 and BMP-4. ,, Therefore, the use of icariin as an alternative substance in dental implants to promote bone formation and osseointegration as well as to prevent peri-implantitis could contribute to implant dentistry and significantly promote its success rate.
| Evaluation of the Hypothesis|| |
Icariin and Alveolar Bone Formation
The risk of alveolar bone resorption after tooth extraction is very high, and the wound may become inflamed in some cases, leading to loss of alveolar bone. Applying icariin to alveolar bone defects after tooth extraction seems beneficial as it prevents bone loss and inhibits inflammation. Moreover, for cases involving bone graft before dental implant surgery, either icariin could reduce the quantities of bone tissue or other substitutes that can be harvested are limited. As icariin also has other effects on the whole body, its addition to the bone graft is a topical method. Therefore, icariin could contribute to bone formation by promoting osteoblast activities, inhibiting osteoclast activities, and preventing excessive bone resorption. The quantities of bone graft could be reduced, and the healing period could be shortened. These warrant further investigation on the ratio of icariin to bone graft.
Icariin and Osseointegration
Bone regeneration around oral titanium implants (i.e., osseointegration) has classically been regarded as similar to that observed after injury or fracture. This healing is traditionally based on the succeeding phases of inflammation, regeneration, and remodeling with possible overlapping on certain occasions. It is known that promoting osteoblast activities and inhibiting the function of osteoclasts can potentially accelerate the process of osseointegration. A lot of studies have been focused on the application of growth factors and gene delivery strategies to promote osseointegration and made great progress. ,, Whereas these methods have their own limitations, for example, growth factors are easily degraded because of their short biological half-lives and the safety and efficacy of using gene therapy for regeneration have yet to be evaluated.  Therefore, more strategies should be explored to facilitate osseointegration.
Icariin could effectively promote bone healing and regeneration by stimulating the differentiation and proliferation of osteoblasts; moreover, it has been used for bone tissue engineering, which may be mediated by activating BMP signaling, thereby amplifying its effects. ,,,,,,,,, Icariin clearly holds potential as a prospective substance for use after dental implant surgery to promote osseointegration.
Icariin and Prevention of Peri-Implantitis
Peri-implantitis, which mainly arises from the bacterial colonization of dental implants and the infection of peri-implant tissues, sometimes occurs after tooth implantation, which leads to chronic bone destruction and may consequently trigger implant failure. The current methods for treating peri-implantitis are mainly composed of mechanical decontamination and local antiseptic or antibiotic treatment. , As icariin has anti-inflammatory effects but no obvious side effects, it likely has more advantages over traditional antibiotic treatment.
In dental implantology, guided bone regeneration using membranes with or without mechanical support is used extensively for bone augmentation of the proposed implant placement site. , Its combination with icariin in dental implant surgery should be considered. Fan et al, developed a successful icariin-loaded chitosan/nano-sized hydroxyapatite system which controls the release kinetics of icariin to enhance bone repairing, offering an intriguing delivery method of osteoinductive agents and a useful scaffold design for bone regeneration. Moreover, Zhang et al, studied the effect of loading icariin on biocompatibility and bioactivity of porous β-TCP ceramic, finding that loaded icariin did not change the biocompatibility of β-TCP ceramic, but enhanced the bioactivity of β-TCP ceramic in vivo. These two above-mentioned delivery systems could be applied in dental implant surgery in order to promote the effects and efficacy of icariin. On the contrary, thermosensitive hydrogel drug delivery systems are considered as useful vehicles for delivering drugs such as honokiol and doxorubicin in a pattern that allows sustained release for a long time, leading to better bioavailability. ,,, Therefore, the use of thermosensitive hydrogel drug delivery systems containing active constituents of icariin fusion, after tooth extraction and dental implant surgery around the implant, represents another alternative method in which icariin could be applied. Some studies showed that the use of icariin with concentrations varied from 10 -12 M to 10 -5 M could get ideal results to activate osteogenic differentiation, but further studies should be needed to explore the precise dosage of icariin in dental implant fields. ,
In conclusion, we hypothesize that icariin with effective delivery vehicles and proper dosage could facilitate bone graft before implantation, promote osseointegration after implantation by activating BMP signaling pathways, and inhibit inflammation. The use of icariin offers a potential means of improving the success rate of dental implant surgery and shortening the treatment period. We believe that this idea is good news to dentists and patients. Further research is thus necessary to explore the precise function and use of icariin in this field.
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