Abstract
Background: Postmenopausal osteoporosis is a common skeletal disorder disease because of estrogen deficiency, characterized by increased bone turnover and reductions in bone mineral density. This disorder is a potential risk factor for dental implant surgery because it could increase the risk of oral infectious disease and decrease osseointegration around implants.
Presentation of the Hypothesis: Angelica sinensis root is one of the herbs most commonly used in China. Angelica sinensis extract (AS extract) has been reported to possess neuroprotective, anti-oxidant, hepatoprotective, anti-osteoarthritis, anti-cancer effects. It has also been utilized as a valuable remedy for anemia, menstrual irregularities, and constipation. Recent studies reveal that the AS extract has anti-osteoporotic effects on ovariectomized rats and could promote the proliferation of human bone cells. We therefore hypothesize that systemically or locally used AS extract could improve osseointegration of dental implants in osteoporosis patients.
Implications of the Hypothesis: Our hypothesis could contribute to provide an option to enhance success ratio of dental implants in postmenopausal osteoporosis by the replenishment of AS extract.
Keywords: Angelica Sinensis; Postmenopausal Osteoporosis; Oestrogen; Dental Implant; Osseointegration
Abbreviations: TCM: Traditional Chinese Medicine, AS: Angelica Sinensis, ALP: Alkalinephosphatase, VOAS: Volatile Oils of Angelica Sinensis
Introduction
Postmenopausal osteoporosis is a common skeletal disorder
disease which has become one of the most important public health
problems in our ageing society. It is mainly caused by estrogen
deficiency, while the lack of estrogen after menopause is associated
with increased osteoblast (bone-forming cell) apoptosis [1].
These factors can lead to the increase of both osteoclastogenesis
and osteoclast activity, eventually causing decreased bone mass
and increased risk for osteoporosis [2]. Furthermore, genetic
and hereditary factors, hormonal status, dietary habits as well
as lifestyle may also involve the development of postmenopausal
osteoporosis [3-5]. Some reports had showed that osteoporosis
could impact the osteointegration owing to the skeletal disorder
and changes of the bone remodeling, which was associated within
creased bone turnover and reductions in bone mineral density [6-
8]. Recent study indicates that inflammation also plays a critical
role in bone remodeling and in pathogenesis of osteoporosis [9,10].
It is well known that the immune and skeletal systems interact
and affect each other [11-14]. Recent years, the most frequently
studied topics concern osteoporosis is focus on the the immune
system, pro-inflammatory cytokines with their receptors and
immunological mechanisms regulating bone metabolism. Oestrogen
plays an important role in the regulation of immune function, and its
receptors have been identified on monocytes, T and B lymphocytes
[15]. Oestrogen deficiency could result in a marked increase in pro inflammatory cytokines, whereas the level of bone-forming factors
is decreased [15,16]. Therefore, oestrogen deficiency may provide a
more susceptible environment for bacteria and lead to the increase
the risk of oral infectious disease, which may have a relationship
with the imbalanced bone status of osteoporosis [17]. These
elements make osteoporosis patients prone to peri-implantitis,
which could be a potential risk factor for implants in dental surgery
because it could decrease bone formation around implants and
then affect osseointegration of dental implants.
Many previous studies have proved that the rate of osseointegration around dental implants is significantly reduced under osteoporotic conditions compared to the normal conditions [18,19]. Therefore, how to avoid implant loss and enhance success ratio of dental implants in postmenopausal osteoporosis patients is always a clinical focus. Angelica Sinensis (AS) root is one of the herbs most widely used in China. AS extract has been reported to possess neuroprotective, anti-oxidant, hepatoprotective, anti-osteoarthritis, anti-cancer effects [20-24]. It has also been utilized in Traditional Chinese Medicine (TCM) as a valuable remedy for anemia, menstrual irregularities, and constipation [25-28]. The diverse biological activities of AS extract mainly depend on the active compounds of phthalides, organic acids, polysaccharides, and flavones [29]. Recently, it has been recognized that the AS extract has anti-osteoporotic effects on ovariectomized rats [30]. Moreover, it could promote the proliferation and differentiation of human bone cells [31]. It also has been suggested that AS extract could inhibit RANKL-mediated osteoclast differentiation in bone marrow macrophages in vitro, indicating that it may serve as a useful drug in the prevention of bone loss [32].
Presentation of The Hypothesis
Our hypothesis is that systemically administration or locally
used AS extract could enhance osseointegration of dental implants
in postmenopausal osteoporosis patients. Then, it could provide an
option to improve success ratio of dental implants in postmenopausal
osteoporosis patients through the replenishment of AS extract.
Angelica sinensis has been always used in traditional prescriptions
for bone and tendon injuries. Hu XM reported that Angelica sinensis
was one of the main ingredients in the Encyclopedia of Esoteric
Prescriptions in TCM of fracture prescriptions [33]. It has shown
that these prescriptions had significant effect in reducing the
time needed for the injured bones to heal. AS extract was found
to directly stimulate the proliferation of human bone cells, and
improve the Alkalinephosphatase (ALP) activity, type I collagen
synthesis of OPC-1 at dose-dependent manner [31]. It is possible
that the extract of Angelica sinensis promoted mineralization of the
organicmatrix, and then speeding up bone formation.
Results of the recent research showed that AS extract could
prevent OVX-induced bone loss with efficacy comparable to that
of estrogen. It significantly decreased the bone (femur) mineral
density (BMD) loss, and the levels of bone turnover markers
including serum ALP, Osteocalcin (OC), and Collagen type I
C-telopeptide (CTx) compared to the OVX control group without
influencing estrogen level were reduced markly [30]. Moreover, the
preliminary study performed by our team recently in vitro indicated
that AS extract could promote the mineralization as well as ALP
activity of MC3T3 in a dose-dependent (Figure1). These results
indicate that AS extract could be an effective natural alternative for
the treatment of postmenopausal osteoporosis (Figures 1 & 2).
AS extract has been demonstrated the inhibitory effects on
RANKL-mediated osteoclast differentiation from macrophages and
bone resorption in vitro, and it also reduced the RANKL-induced
expression of osteoclastic marker genes. Furthermore, AS extract
weakened the activation of RANKL-induced signaling pathway including
ERK, p38, JNK, NF-κB, AP-1and NFATc1 [32]. This observation
suggests that AS extract may as a potential drug in the therapy
for disorders associated with bone loss. Angelica sinensis has
been used alone, or in combination with other traditional Chinese
herbs, to treat various inflammatory diseases [34-36]. AS extract
was found to have anti-inflammatory effects and activates the Nrf2
pathway, which protects against oxidative stress [37]. The aqueous
extract of Angelica sinensis can inhibit wear debris particles-induced
osteolysis through its ability of inhibiting TNF-α and IL-1β
release by macrophages, providing a new possible way to prevent
and treat aseptic loosening after total joint replacement [38].
In addition, Zhang WQ et al showed that the other form of
Angelica sinensis, Volatile Oils of Angelica Sinensis (VOAS), could
intervened in the metabolic process of inflammation by altering
histidine metabolism, tryptophan metabolism, arachidonic acid
metabolism, steroid hormone biosynthesis, fatty acid metabolism
and energy metabolism. Metabonomics was used to reflect an
organism’s physiological and metabolic state comprehensively, and
the VOAS was regarded as a potentially powerful tool that reveals
anti-acute-inflammatory mechanism [39]. Therefore, the antiinflammatory
properties of AS extract may be a major component
of its beneficial effects on promotion of osseointegration of dental
implants in postmenopausal osteoporosis.
Implications of The Hypothesis
Postmenopausal osteoporosis poses a significant threat to millions of postmenopausal women. The lack of estrogen after menopause could activate Rank/Rankl/OPG signaling or TNF-α/ IL-1 signaling which directly or indirectly stimulates osteocalst differentiation while inhibit osteoblast differentiation, and then resulting in bone loss as well as microarchitectural deterioration including bone fragility and an increased risk of fracture. Recent investigation has demonstrated that AS extract could prevent bone loss in OVX rats [30].AS extract could directly inhibit Rank/Rankl/ OPG signaling and further prevent osteoclast differentiation [32]. Furthermore, AS extract also could decrease the OVX-induced serum TNF-α and IL-1 levels and indirectly inhibit Rank/Rankl/ OPG signaling, then leading to osteoclast differentiation reduced while osteoblast differentiation increased (Figure 2). Accordingly, to provide an option to improve success ratio of dental implants in osteoporosis patients, we hypothesize that systemically or locally used AS extract could enhance osseointegration of dental implants in postmenopausal osteoporosis patients.
Conclusion
This hypothesis may contribute to provide an approach to decrease the failure ratio of dental implants in postmenopausal osteoporosis. However, further studies must be performed to prove our hypothesis.
Acknowledgement
None.
Funding
This study was supported by Grants from the Open Project of Shandong Provincial Key Laboratory of Oral Tissue Regeneration: SDKQ201905.
Authors’ Contributions
Shimao Yang conceived the idea and formulated the main lines of the theory. Fei Gao performed data collection wrote the paper. All authors read and approved the final manuscript.
Competing Interests
The author declares that they have no competing interests.
Consent for Publication
Not applicable. Ethics approval and consent to participate.
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