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ORIGINAL ARTICLE
Year : 2014  |  Volume : 4  |  Issue : 1  |  Page : 16-21

Influence of estrogen deficiency status on bone around previously osseointegrated dental implants in ovariectomized rats


1 Dental Surgeon at Private Dental Clinic, Alexandroupoli, Evros, Greece
2 Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Greece

Date of Web Publication19-Apr-2014

Correspondence Address:
Dimopoulou Eleni
Thoukudidou 6, 68100 Alexandroupoli, Evros
Greece
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-6781.130946

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   Abstract 

Objective: The aim of this review is to reveal whether there is a risk of failure of previously osseointegrated dental implants in women with estrogen deficiency status.
Background: It is well known that estrogen deficiency can provoke bone alterations leading to bone loss, bone fragility and increased risk of fractures. Consequently, these changes in bone metabolism can affect the surrounding bone tissue of osseointegrated dental implants implicating estrogen deficiency status as a risk factor for their maintenance.
Materials and Methods: Databases were searched (MEDLINE/PubMed) using different combinations of various keywords. Titles and abstracts that satisfied the eligibility criteria were screened by the authors and checked for agreement.
Results: Five studies were included. All studies used rats as models. Two studies reported that estrogen deficiency may cause a negative effect on osseointegration around dental implants. Two studies suggested that estrogen privation results in a negative influence on bone around implants but this effect mainly appears in the cancellous region leaving cortical bone slightly affected. There is only one study that cited that estrogen deficiency may not be accused of being a risk factor for the failure of osseointegrated dental implants in ovariectomized rats.
Conclusion: Estrogen deficiency status in rats seems to affect the success rates of previously osseointegrated dental implants but this situation seems to concern implants located in maxilla. Further investigation needs to be made in order to reveal whether the same results can be shown in women.

Keywords: Deficiency, estrogen, implant, osseointegration


How to cite this article:
Eleni D, Lazaros T. Influence of estrogen deficiency status on bone around previously osseointegrated dental implants in ovariectomized rats. J Dent Implant 2014;4:16-21

How to cite this URL:
Eleni D, Lazaros T. Influence of estrogen deficiency status on bone around previously osseointegrated dental implants in ovariectomized rats. J Dent Implant [serial online] 2014 [cited 2022 Aug 12];4:16-21. Available from: https://www.jdionline.org/text.asp?2014/4/1/16/130946


   Introduction Top


It is well known that treatment of edentulous patients is better succeeded with dental implant therapies in most cases. This way of rehabilitating these patients has nowadays become a routine procedure and in the years to come more and more postmenopausal women will carry dental implants that have been placed in the past. [1] Albrektsson et al. (1998) suggested that continued firm osseointegration in the jaw bone affects the maintenance of satisfactory function of dental implants. [2] Consequently, alterations of the surrounding bone may affect the osseointegration of previously inserted dental implants.

The form of osteoporosis most common in women after menopause is referred to as primary type 1 or postmenopausal osteoporosis. Osteoporosis is caused by the loss of function of ovaries which provokes a decrease in estrogen levels. This estrogen deficiency increases bone turnover, where bone resorption exceeds bone formation.[3],[4] Thus, postmenopausal women are characterized by an accelerated phase of bone loss, bone fragility and increased risk of fractures. These changes in the bone metabolism of postmenopausal women might affect the high predictability rates of dental implants [5] implicating osteoporosis as a potential risk factor for the success of dental implants.

It has been already proved that osseointegration of newly inserted dental implants in patients with established osteoporosis can be negatively influenced by alterations either in the preexisting or the newly formed bone. [6] It is suggested that these effects mainly appear in the cancellous bone and as a result dental implants placed in the maxillary bone are more prone to implications in bone healing. [7],[8],[9],[10] In a study by Duarte et al. (2005), it was proved that alendronate treatment therapy may prevent this negative influence as well as estradiol replacement therapy does, but, in contrast to estradiol this positive effect is sustained after alendronate's withdrawal. [11] There is a smaller amount of studies investigating the effect of osteoporosis and estrogen deficiency on dental implants that have been already osseointegrated. [12],[13] Additionally, there are other studies evaluating this effect and trying to figure out whether estrogen and alendronate therapies on postmenopausal bone loss can prevent this negative effect. [1],[14] Therefore, a question arises whether it can be determined that the systemic bone mass loss caused by menopause affects previously inserted dental implants.

Ovariectomy (OVX) is considered as the most effective protocol to induce estrogen deficiency osteopenia in order to achieve a similar hormonal deficiency status to that of menopause. [15] This is due to the fact that on these circumstances (estrogen deprivation), it appears that rats tend to imitate the anatomic and kinetic patterns of loss of bone mass appeared in humans. [15],[16] Considering these studies, all researchers use ovariectomized rats to create a model of estrogen deficiency status similar to that of postmenopausal women. The aim of the present literature review is to shed light on the influence of estrogen deficiency status on bone around previously osseointegrated dental implants.


   Materials and Methods Top


Focused question

The addressed focused question was "Does estrogen deficiency in postmenopausal women affect the osseointegration of previously inserted dental implants?''

Eligibility criteria

The selection criteria included the following: 1) original articles; 2) human or rat studies; 3) reference list of original and review studies; 4) use of statistical methods; 5) intervention (control treatment groups, sham operated and OVX treatment groups after implant placement); and 6) articles published in English.

Search strategy

The authors searched the MEDLINE/PubMed (National Library of Medicine, Bethesda, Maryland) databases for appropriate articles using the following keywords in various combinations: "estrogen'', "deficiency'', "osseointegration'', "implant''. Nineteen results appeared and titles and abstracts that satisfied the eligibility criteria were screened by the authors and checked for agreement. The summary of the full list of articles to be relevant were read and 14 articles were excluded because the focused question was not addressed. In total, 5 studies were included and processed for data extraction [Table 1]. Because of the limited number of studies, the structure of the present study was customized to mainly summarize the relevant information.
Table 1: Studies that performed ovariectomy on rats after the implant placement surgery

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   Results Top


In total, five studies were reported that performed ovariectomy on rats after the implant placement surgery. No human studies were found. There was a study that operated implant surgery and ovariectomy or sham surgery at the same time, so it was excluded from our review because the osseointegration of the dental implant was not yet achieved before the estrogen privation. [17] Two of the studies reported in our review investigated the fact whether the established osseointegration is affected by estrogen deficiency using two treatment groups (OVX and sham operated) [13],[18] while the other three used additional treatment groups (OVX and ALD treatment, OVX and hormone replacement) in their effort to shed light on assumptions that hormone replacement or alendronate therapies may reduce the negative effects of estrogen deficiency. The results of the above treatment groups were not taken into consideration for this literature review because they did not apply with the criteria of the focused question and information on the results of OVX operated rats; sham operated and control groups were gathered and investigated separately.

Two studies [1],[19] reported that estrogen deficiency may cause a negative effect on osseointegration around dental implants. Giro et al. (2007) observed lower values of bone mineral density around implants, a systemic impairment of animals after densitometry of femur and lumbar vertebrae and lower torque needed to remove implants in OVX treatment groups. [19] Giro et al. (2011), in a more recent study, using additional histological and biochemical measures concluded that bone around implants can be affected negatively when estrogen suppression occurs. This study showed significant lower BMD (bone mineral density), BIC (bone to implant contact), BAFO (bone area fraction occupancy) and MAR (mineral apposition rate) rates in the OVX group. Furthermore, an increase of OCN serum concentration (osteocalcin) resulted in an increase of bone resorption to bone formation ratio and higher DPD (deoxypyridinoline) excretion values were observed in the OVX group. Conclusively, this shows an increased osteoclastic activity in surfaces around implants that are deficient of estrogen but further investigation regarding bone turnover kinetics should be carried out. [1]

Two studies suggested that estrogen privation results in a negative influence on bone around implants, but mainly in the cancellous region while the cortical zone is slightly affected revealing no statistically significant difference. [14],[18] Specifically, Giro et al. (2008) [14] revealed that the bone density measured by digital radiographs at 6 points on sides of the implant was decreased in the cancellous zone in the OVX treatment groups. Similarly, Pan et al. (2000), reported that regarding the cancellous bone the contact area and the bone density showed a significant gradual loss during the period between 28 th and 168 th day after the OVX operation compared with sham operated while in the cortical zone such contact once attained is not affected by estrogen conditions. This study, suggested that estrogen deficient conditions may amplify the systemic bone resorption (gradual loss of Unit Bone Mass on the test group compared with the Control group was observed) not only in the preexisting cancellous bone but also in the newly formed trabeculae around implants placed in a nonfunctional site. This gradual loss of continuity between bone trabeculae and also between the trabeculae bone and the new bone adjacent to the implant placed in an nonfunctional site is prone to a diminished support of dental implants. [18]

Contrary to the previous studies, Giro et al. (2011) proved that BIC and BAFO results did not differ between the OVX operated and sham operated regardless of the decrease of systemic bone density and alterations in bone turnover markers shown in the OVX groups. As a result, estrogen deficiency may not be accused of being a risk factor for osseointegrated implant failure in the jaw bone. [13]


   Discussion Top


It has been proved that deficiency of estrogens (17β-estradiol), which occurs after ovariectomy and during menopause causes an increase of cytokines, including interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) and IL-6, who are responsible for the formation of osteoclasts and thus the increase of osteoclastic activity. [20],[21] Estrogen deficiency may also enhance osteoclastogenesis by an increase of RANK (receptor activator of nuclear factor - kappa B) ligands or by down-regulating OPG (osteoprotegerin) expression in osteoclasts exerting a resorptive effect on bone. [22],[23] As a result, the estrogen privation provoked after menopause results in a reduction of bone mass. Therefore, a question arises whether this bone mass loss may result in a decrease in the contact area between a dental implant and the surrounding bone tissue. [18] According to this review, few authors have conducted investigations regarding this question, so a systematic literature review is needed.

Ovariectomy has been described as the most reliable model to induce estrogen deficiency in rats with similar results as in menopause in women. [15] All the studies mentioned above used ovariectomized mature female rats as models. All the researches listed in the present review operated implant placement surgery on the tibiae of female rats with the exception of one research where implants were placed on maxilla. [13] Sixty days after the implant placement, the control group rats were euthanized, the OVX group rats were ovariectomized and fiction surgery was performed to the sham group rats. The OVX and sham groups were euthanized 90 days after. In the study of Pan et al. (2000), [18] OVX or sham operation was carried out 168 days after the implant placement and the rats were euthanized 28 days, 84 days and 168 days after. Thus thorough examination of the progressive effects of estrogen deficiency was made. The OVX-related alterations in bone tissue can be observed histologically after a 30-day period post-ovariectomy, [24] which is the reason the studies used a 90-day estrogen privation interval before euthanasia.

The authors of the researches included used different methods to evaluate the amount of osseointegration such as histological (all except 14,15), biochemical, [1] by digital radiographs which are capable of producing the same results as histological studies, [14],[25],[26] torque removal [19] and densitometry of femur and lumbar vertebrae by dual-energy X-ray [19] to confirm systemic impairment.

The reported studies used the same treatment groups, similar methods, coinciding implant healing period time and similar estrogen privation time. Therefore, their results are comparable.

In overall, two out of five studies claim that cancellous bone is more susceptible to alterations [14],[18] such as lower BD, BAFO, MAR, BIC rates and, also, to an increase in osteoclastic activity while a contact between implant and cortical bone once attained is less likely to be negatively affected by hormone levels. [18] This difference may be attributed to the fact that bone remodeling of the cancellous bone is 10 times greater than that of the cortical bone. [27] The different results observed in these regions may also be explained by the thinning of trabeculae which leads to an increase in medullar spaces and a lower bone mineral density in the cancellous bone. [18],[28] Therefore the contact between implants and the new bone adjacent may be jeopardized. However, further investigations of the results of biomechanical stimulus from occlusion on the surrounding bone tissue around dental implants must be conducted due to the fact that all the rat models used in these studies were accomplished in a nonfunctional in vivo model while it is known that the stimulation of implants may affect the bone remodeling procedures around the implants. [18] In this regard, it is suggested that further clinical research should be made in order to confirm possible implications in the osseointegration of dental implants on women with estrogen deficiency and whether hormone replacement therapy or treatment with bisphosphonates can reduce the negative effects.


   Conclusion Top


Within the limits of this present review, it is concluded that estrogen deficiency may affect the success rates of previously osseointegrated dental implants located in maxilla but this cannot be clearly demonstrated due to the fact that there are no human studies and the amount of studies using rats as models is limited.


   Acknowledgment Top


The authors report no conflicts of interest related to this study.



 
   References Top

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10.Motohashi M, Shirota T, Tokugawa Y, Ohno K, Michi K, Yamaguchi A. Bone reactions around hydroxyapatite-coated implants in ovariectomized rats. Oral Surg Oral Med Oral pathol Oral Radiol Endod 1999;87:145-52.  Back to cited text no. 10
    
11.Duarte PM, de Vasconcelos Gurgel BC, Sallum AW, Filho GR, Sallum EA, Nociti FH Jr. Alendronate therapy may be effective in the prevention of bone loss around titanium implants inserted in estrogen-deficient rats. J Periodontol 2005;76:107-14.  Back to cited text no. 11
    
12.Pan J, Shirota T, Ohno K, Michi K. Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats. J Oral Maxillofac Surg 2000;58:877-82.  Back to cited text no. 12
    
13.Giro G, Coelho PG, Sales-Pessoa R, Pereira RM, Kawai T, Orrico SR. Influence of estrogen deficiency on bone around osseointegrated dental implants: An experimental study in the rat jaw model. J Oral Maxillofac Surg 2011;69:1911-8.  Back to cited text no. 13
    
14.Giro G, Gonçalves D, Sakakura CE, Pereira RM, Marcantonio Júnior E, Orrico SR. Influence of estrogen deficiency and its treatment with alendronate and estrogen on bone density around osseointegrated implants: Radiographic study in female rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:162-7.  Back to cited text no. 14
    
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17.Carvalho MD, Benatti BB, César-Neto JB, Nociti FH Jr, da Rocha Nogueira Filho G, Casati MZ, et al. Effect of cigarette smoke inhalation and estrogen deficiency on bone healing around titanium implants: A histometric study in rats. J Periodontol 2006;77:599-605.  Back to cited text no. 17
    
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