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Original Hypothesis

Icariin: Can an herbal extract enhance dental

implant outcomes?
Qiang Wang1,2, Xiaoying Wang1, Xin Xu1
1
Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, Shandong
2
Department of Prosthodontics, Jinan Stomatological Hospital, Jinan, PR China

A B S T R A C T

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.

Key words: Dental implant, icariin, osseointegration

Introduction surgery. Besides, research has also shown that peri-

implantitis is one of the main causes of dental implant
Dental implant is an established alternative for replacing failure. To date, no ideal treatment method has been
missing teeth. It is regarded as a good option to restore reported to solve these problems.
the normal function, speech, health, and esthetics of
patients regardless of injury, disease, or atrophy of the An adequate volume of bone surrounding a dental
stomatognathic system.[1] Dental implants are more implant is essential for the success of surgery.[2,3] Under
comfortable and efficient compared with traditional normal circumstances, tooth loss due to different reasons
restorative materials such as fixed and removable may lead to alveolar resorption, such as tooth extraction,
dentures. An increasing number of patients with trauma, and periodontal disease. In addition, shortage of
bone can hinder proper positioning of a dental implant
tooth loss tend to choose dental implants, but they do
according to prosthetic needs and treatment planning,
complain about the long treatment period, which lasts
unless the volume of hard and soft tissues is increased
6 months or so, longer than that involving traditional
before implantation. On the contrary, it is essential not
procedures. Dentists also face many challenges, such as
only to achieve well-anchored implants but also to obtain
inadequate alveolar bone volume before dental implant
natural-looking esthetic results. Various procedures to
reconstruct lost tissue, such as autogenous bone graft
Access this article online and allogeneic bone graft,[4] are available, and one
Quick Response Code: current intriguing strategy is to apply a substance that
Website: could ultimately be confirmed as an agent of choice for
www.dentalhypotheses.com
the clinical promotion of bone healing and regeneration
DOI: to the bone grafts (e.g., bone morphogenetic protein
10.4103/2155-8213.106836 [BMP] and other biological molecules).[5,6] However, the
clinical application thereof remains a challenge.

Corresponding Author: Prof. Xin Xu, Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology,
Shandong University, 44-1 Wenhuaxi Road, 250012 Jinan, Shandong, PR China. E-mail: [email protected]

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Wide bone-to-implant direct contact is crucial for the activities and inhibiting osteoclast activities.[15-19] Icariin
long-term clinical success of endosseous dental implant has been reported to be a strong candidate as an osteogenic
surgery. This condition is called osseointegration. The compound for use in bone tissue engineering.[20]
classic dental implant treatment requires a long healing In spite of these findings, the precise mechanism of
period, which usually varies from 3 months to more icariin remains unclear. Some studies found that icariin
than 6 months. During this period, bone regeneration has a direct stimulatory effect on the proliferation and
and healing between the implant and bone occur, as differentiation of cultured human osteoblasts in vitro,
does osseointegration. Many studies have focused which may be mediated by increasing the production of
on how to shorten the healing time and speed up bone morphogenetic proteins 2 (BMP-2) in osteoblasts.[21]
the process of osseointegration. This process may be Other studies have demonstrated that icariin exerts
accelerated by altering the implant’s surface roughness, its potential osteogenic effects by inducing Runx2
by developing a biomimetic interface, or via local expression, producing BMP-4, and activating BMP
delivery of growth-promoting factors.[6-10] There is an signaling.[22,23] Hsieh et al, reported that icariin inhibits
ongoing effort in the research community to contribute osteoclast differentiation and bone resorption via the
to the osseointegration process. suppression of Mitogen-activated protein kinase/NF-
kappa B (MAPK/NF-kB)-regulated hypoxia-inducible
Peri-implantitis is an inflammatory reaction of the tissues factor-1a (HIF-1a) and PGE2 synthesis.[24] In addition,
around an osseointegrated dental implant that results in icariin is regarded as a safe and effective natural anti-
loss of the supporting bone. It has an incidence rate of inflammatory drug. Chen [25] demonstrated that an
approximately 5-8%, which limits the clinical success icariin derivative can inhibit inflammation through
of the surgery. Its common causes include unhealthy the suppression of p38 mitogen-activated protein kinase
prosthesis, bacterial infection, smoking, and occlusion and nuclear factor-kappaB pathways.
interference, among others. Peri-implantitis could be
affected by the periodontal status of neighboring teeth, The Hypothesis
bone quality, surgical technique, and general health of the
patient. Current methods for preventing and treating peri- Chinese herbal medicine has numerous advantages
implantitis include mechanical, chemical, electrochemical, that an increasing number of researchers have
or thermal decontamination, or any combination of these expressed interest in it. It is relatively safe and cheap,
methods so that the surfaces can be further modified or making it worthwhile to explore and characterize its
altered in a favorable fashion to accommodate, facilitate, further uses. As icariin possesses intriguing activities
or promote more biofunctionality and bioactivity.[11,12] At associated with the success rate of dental implant
present, much of the information on the effectiveness of surgery, promoting osteoblast activities, inhibiting
these interventions is obtained from case reports such that osteoclast activities, and inhibiting inflammation,[13-25] it
no evidence-based consensus has been reached as to which is reasonable to hypothesize that icariin can positively
option is clinically most advantageous. More strategies to affect dental implant surgery including contributing
prevent and treat peri-implantitis should be developed. to bone formation before implant surgery, promoting
osseointegration, and preventing peri-implantitis.
Icariin is the main effective constituent of epimedium,
which is one of the most frequently used Chinese BMPs are well known to be effective biological molecules
herbal medicines to treat impotence, improve sexual that stimulate bone formation, and they are widely
function, and enhance immune function.[13,14] It has used for bone tissue engineering. Recent studies have
been demonstrated to act as a phosphodiesterase 5 shown that recombinant human BMP-2 absorbed into
(PDE5) inhibitor, enhance the production of bioactive bovine type-1 collagen sponges consistently stimulates
nitric oxide, and mimic the effects of testosterone. It bone formation effectively at graft sites. However,
has also exhibited antioxidant, antidepressant, and the application of BMPs is relatively expensive, and
nootropic effects in animal studies, as well as for several these molecules are easily degraded when applied
other indications. Pharmacologic studies have shown alone.[26] Abundant evidences have shown that icariin
that icariin is a flavonol, a type of flavonoid. could amplify their function by activating BMP
signaling systems, such as BMP-2 and BMP-4. [21-23]
Recent studies have shown that icariin could promote Therefore, the use of icariin as an alternative substance
bone formation and regeneration effectively and exerts in dental implants to promote bone formation and
its anti-osteoporotic effects by activating osteoblast osseointegration as well as to prevent peri-implantitis

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Wang, et al.: The potential use of icariin in implant dentistry

could contribute to implant dentistry and significantly Icariin and Prevention of Peri-Implantitis
promote its success rate. Peri-implantitis, which mainly arises from the bacterial
colonization of dental implants and the infection of
Evaluation of the Hypothesis peri-implant tissues, sometimes occurs after tooth
implantation, which leads to chronic bone destruction
Icariin and Alveolar Bone Formation and may consequently trigger implant failure. The
The risk of alveolar bone resorption after tooth extraction current methods for treating peri-implantitis are mainly
is very high, and the wound may become inflamed in composed of mechanical decontamination and local
some cases, leading to loss of alveolar bone. Applying antiseptic or antibiotic treatment.[11,12] As icariin has
icariin to alveolar bone defects after tooth extraction anti-inflammatory effects but no obvious side effects,
seems beneficial as it prevents bone loss and inhibits it likely has more advantages over traditional antibiotic
inflammation. Moreover, for cases involving bone graft treatment.
before dental implant surgery, either icariin could reduce
the quantities of bone tissue or other substitutes that In dental implantology, guided bone regeneration using
can be harvested are limited. As icariin also has other membranes with or without mechanical support is used
effects on the whole body, its addition to the bone graft extensively for bone augmentation of the proposed
is a topical method. Therefore, icariin could contribute implant placement site. [1,27] Its combination with
to bone formation by promoting osteoblast activities, icariin in dental implant surgery should be considered.
inhibiting osteoclast activities, and preventing excessive Fan et al,[28] developed a successful icariin-loaded
bone resorption. The quantities of bone graft could be chitosan/nano-sized hydroxyapatite system which
reduced, and the healing period could be shortened. controls the release kinetics of icariin to enhance bone
These warrant further investigation on the ratio of repairing, offering an intriguing delivery method of
icariin to bone graft. osteoinductive agents and a useful scaffold design for
bone regeneration. Moreover, Zhang et al,[29] studied
Icariin and Osseointegration the effect of loading icariin on biocompatibility and
Bone regeneration around oral titanium implants (i.e., bioactivity of porous β-TCP ceramic, finding that
osseointegration) has classically been regarded as loaded icariin did not change the biocompatibility
similar to that observed after injury or fracture. This of β-TCP ceramic, but enhanced the bioactivity of
healing is traditionally based on the succeeding phases β-TCP ceramic in vivo. These two above-mentioned
of inflammation, regeneration, and remodeling with delivery systems could be applied in dental implant
possible overlapping on certain occasions. It is known surgery in order to promote the effects and efficacy of
that promoting osteoblast activities and inhibiting icariin. On the contrary, thermosensitive hydrogel drug
the function of osteoclasts can potentially accelerate delivery systems are considered as useful vehicles for
the process of osseointegration. A lot of studies have delivering drugs such as honokiol and doxorubicin in
been focused on the application of growth factors and a pattern that allows sustained release for a long time,
gene delivery strategies to promote osseointegration leading to better bioavailability.[30-33] Therefore, the use
and made great progress.[8-10] Whereas these methods of thermosensitive hydrogel drug delivery systems
have their own limitations, for example, growth factors containing active constituents of icariin fusion, after
are easily degraded because of their short biological tooth extraction and dental implant surgery around
half-lives and the safety and efficacy of using gene the implant, represents another alternative method in
therapy for regeneration have yet to be evaluated.[26] which icariin could be applied. Some studies showed
Therefore, more strategies should be explored to that the use of icariin with concentrations varied from
facilitate osseointegration. 10-12 M to 10-5 M could get ideal results to activate
osteogenic differentiation, but further studies should
Icariin could effectively promote bone healing and be needed to explore the precise dosage of icariin in
regeneration by stimulating the differentiation and dental implant fields.[23,34]
proliferation of osteoblasts; moreover, it has been used
for bone tissue engineering, which may be mediated In conclusion, we hypothesize that icariin with effective
by activating BMP signaling, thereby amplifying delivery vehicles and proper dosage could facilitate bone
its effects.[15-24] Icariin clearly holds potential as a graft before implantation, promote osseointegration after
prospective substance for use after dental implant implantation by activating BMP signaling pathways,
surgery to promote osseointegration. and inhibit inflammation. The use of icariin offers a

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journal
Wang, et al.: The potential use of icariin in implant dentistry

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Wang, et al.: The potential use of icariin in implant dentistry

32. Xun W, Wu DQ, Li ZY, Wang HY, Huang FW, Cheng SX, et al. deficiency and activates oestrogen receptor-dependent
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enhance dental implant outcomes?. Dent Hypotheses 2012;3:133-7.
sustained release of doxorubicin: Rheological characterization
and in vivo evaluation in rats. Drug Deliv 2011;18:305-11. Source of Support: This work was supported by the National
34. Mok SK, Chen WF, Lai WP, Leung PC, Wang XL, Yao XS, Natural Science Foundation of China (grant No.30901673),
Conflict of Interest: None declared
et al. Icariin protects against bone loss induced by oestrogen

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