Is oestrogen associated with mandibular condylar resorption? A systematic review

Abstract

A systematic review of the literature was performed regarding the influence of oestrogen on the occurrence of mandibular condylar resorption. Search terms for oestrogen were used in combination with terms related to the effect on condylar remodelling. A search of the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases yielded 419 articles published between October 1993 and March 2017. An additional 48 articles were retrieved through manual searching of the reference lists. After initial abstract selection, 94 eligible articles were screened in detail, resulting in a final number of 33 articles included in the review. From this review, no evidence was found that oestrogen (deficiency) contributes to mandibular condylar resorption. The conclusions are limited by the lack of studies with a high level of evidence. Further investigations on serum oestrogen concentrations in women with condylar resorption are needed. Moreover, future studies should focus on the effects of the different types of medication and diseases influencing oestrogen concentrations, the utility of oestrogen concentrations during preoperative screening, and the policies for managing orthognathic surgery patients with an oestrogen deficiency. Finally, whether the mechanisms and risk factors that lead to idiopathic condylar resorption are the same in condylar resorption following orthognathic surgery remain to be elucidated.

Condylar resorption is a multifactorial condition that affects the mandibular condyle and is characterized by changes in the condylar shape and a decrease in condylar mass. These changes can lead to malocclusion, temporomandibular joint (TMJ) dysfunction, and pain . There are a number of local and systemic factors and/or pathologies that are associated with condylar resorption. When the specific cause is unknown, the condition is commonly termed idiopathic condylar resorption (ICR), also known as idiopathic condylysis, condylolysis, condylar atrophy, and progressive or aggressive condylar resorption .

Because condylar resorption occurs more frequently in women than in men, many have thought that a prominent systemic factor for the pathogenesis of this disease might be related to sex hormones, particularly oestrogens . Several studies have shown the presence of high-affinity oestrogen receptors in the synovial membrane, articular disc, and mandibular condyle of females , and also the potential effect of oestrogen on the metabolic activity of the TMJ . The oestrogen deficiency in postmenopausal women elicits bone loss in the vertebrae and long bones resulting in bone fractures, and this condition is called postmenopausal osteoporosis . While considerably less information is available on mandibular condyle bone loss under oestrogen-deficient conditions , two clinical studies have reported that female patients presenting ICR have low serum levels of 17β-oestradiol , suggesting a possible relationship between oestrogen deficiency and condylar resorption.

This systematic review was performed to investigate the effects of oestrogen on condylar resorption in order to determine whether oestrogen should be considered a risk factor for condylar resorption.

Materials and methods

Search strategy

A systematic review of the literature was conducted concerning the influence of oestrogen on mandibular condylar resorption; the PRISMA guidelines were followed . The electronic databases PubMed (National Library of Medicine, NCBI), Cochrane Central Register of Controlled Trials, and Embase were searched to identify relevant articles; the search covered the period from database inception to March 2017. Search terms for oestrogen were used in ‘AND’ combination with search terms of condylar resorption, mandibular condyle, temporomandibular joint, synovial membrane, cartilage, condylysis, condylolysis, and osteoarthritis ( Table 1 ). Search terms included controlled terms from medical subject headings (MeSH) in PubMed and Emtree in EMBASE, as well as free text terms in the Cochrane Library. The references of the articles identified were searched for additional relevant publications.

Table 1
Search terms used in this review.
Primary key words Secondary key words
Oestrogen Condylar resorption
Oestrogen receptor Mandibular condyle
Oestradiol Temporomandibular joint
Female hormones Synovial membrane
Sex hormones Cartilage
Contraceptive agents Condylysis
Hormone therapy Condylolysis
Menopause Osteoarthritis
Menopausal
Menstrual cycles
Ovariectomy
Ovarian cancer

Study selection and inclusion criteria

Two reviewers (LFPN and EAA) independently screened all potentially relevant titles and abstracts against pre-specified eligibility criteria. When the abstract did not provide sufficient information, the full text article was checked against the eligibility criteria. All discrepancies were resolved through a discussion and consensus procedure.

Peer-reviewed and non-peer-reviewed articles were considered. Articles were included when (1) they reported oestrogen and condylar resorption or an interaction with the TMJ, (2) the full text was available in the English language, and (3) they reported human clinical trials, randomized and prospective studies, case series, in vitro human simulation studies, and multicenter and comparative studies. Exclusion criteria were (1) animal studies, (2) literature reviews, (3) case reports, (4) congress abstracts, (5) opinion articles, (6) no available translation, and (7) no full text available in international libraries.

Articles on the effects of oestrogen on TMJ osteoarthritis (TMJ OA) were included, as it is hypothesized that similar hormonal receptor effects and disease mechanisms may play a role. Similarly, articles on the effects of oestrogens on temporomandibular disorders (TMD) without further specification were also included, because condylar resorption is included in the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD).

The initial search yielded a total of 419 articles published between October 1993 and March 2017. An additional 48 relevant publications were retrieved through manual searching of the reference lists of the articles identified, giving a total of 467 articles. The review and selection procedure resulted in the exclusion of 326 articles at title screening and 47 articles based on the content of the abstract. Of the remaining 94 articles, 61 were excluded at the full-text reading stage for the following reasons: (1) seven articles were not available in English, (2) 10 articles were not available in international libraries, (3) one article had been published twice in two different journals, (4) four were congress abstracts, and (5) 39 were not relevant. The entire selection process therefore resulted in a total of 33 articles. These articles were included in the present systematic review.

A flowchart of the literature search and selection process through the different stages of the systematic review (PRISMA) is given in Fig. 1 .

Fig. 1
Flowchart of the search strategy and study selection using PubMed, Embase, and the Cochrane Library.

Results

This systematic review included 33 articles, which were divided into three groups by subject area covered: (1) oestrogen in clinical cases of condylar resorption ( n = 3), (2) mechanisms by which oestrogen affects the TMJ ( n = 11), and (3) other oestrogen-related TMD ( n = 20) ( Table 2 ). One article was included in group 2 and group 3.

Table 2
Assignment of the 33 articles identified to the three subject categories.
Category References Number of papers
Oestrogen in clinical cases of condylar resorption 3
Mechanisms for oestrogen-related condylar resorption and TMD 11
Other oestrogen-related TMD 20
TMD, temporomandibular disorder.

When classified according to the level of evidence, there were two randomized clinical trials (RCTs), 10 cohort studies, nine case–control studies, seven cross-sectional studies, and five in vitro studies ( Table 3 ).

Table 3
Level of evidence of the studies included.
Study design References Number of papers
Randomized clinical trial 2
Cohort 10
Case–control 9
Cross-sectional 7
In vitro 5
Total 33

Oestrogen in clinical cases of condylar resorption

Three articles were classified under this topic ( Table 4 ). Two articles reported a tendency of low serum levels of 17β-oestradiol in female patients with ICR . One article showed no association between oral contraceptive use and the development of aggressive condylar resorption after orthognathic surgery in patients with TMJ OA .

Table 4
Level of evidence of the studies on oestrogen in clinical cases of condylar resorption.
Study design References Number of papers
Cohort 3
Total 3

Mechanisms by which oestrogen affects the TMJ

Eleven articles were assigned to this topic ( Table 5 ). Three in vitro studies investigated the presence of oestrogen receptors in the human TMJ disc . While the first was confirmatory, reporting a difference between sexes, the second and third studies reported negative findings for oestrogen binding sites.

Table 5
Level of evidence of the studies on the mechanisms by which oestrogen affects the TMJ.
Study design References Number of papers
Cohort 1
Case–control 4
Cross-sectional 1
In vitro 5
Total 11
TMJ, temporomandibular joint.

Two in vitro studies distinguished between the relative expression of oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) . The first investigated the effect of oestrogen on the expression of oestrogen receptors and showed a decrease in ERα and an increase in ERβ following the application of 17β-oestradiol . The authors differentiated between the effect of oestrogen on bone and the effect of oestrogen on inflammation of the TMJ. The results showed that oestrogen prevents bone resorption by upregulating osteoprotegerin (OPG) production in the OPG–RANKL pathway and increases inflammation in women with external exacerbating factors, through mediators that increase macrophage colonization. The second study showed that ERβ was expressed at significantly lower levels in samples from TMD-derived monocytes, collected in the early follicular phase (low serum oestrogen levels) . In addition, the authors found that the oestrogen-induced monocytic response in TMD-derived monocytes was correlated with pain in women with TMD.

Six articles investigated the presence of oestrogen receptor gene polymorphism in patients with TMD compared with controls .

Other oestrogen-related TMD

Twenty articles reported the relationship between oestrogen and TMD, without mentioning condylar resorption ( Table 6 ).

Table 6
Level of evidence of the studies on TMD influenced by oestrogen.
Study design References Number of papers
Randomized clinical trial 2
Cohort 6
Case–control 5
Cross-sectional 7
Total 20
TMD, temporomandibular disorders.

Four articles investigated serum concentrations of oestrogen in people suffering from TMD: two case–control studies demonstrated that higher levels of oestrogen may be implicated in the pathophysiology of TMD, while two cross-sectional studies found no association between oestrogen levels and TMD .

Ten articles looked into the effects of exogenous oestrogen in TMD: oral contraception and oestrogen replacement therapy . One RCT showed greater pain improvement in women with a normal cycle compared to those using oral contraceptives 1 year after self-managed pain treatment . In contrast, two cohort studies found that women with TMD taking oral contraceptives had more stable palpation pain across their menstrual cycles than women with TMD not taking oral contraceptives . One case–control study and one cross-sectional study found a higher prevalence of orofacial pain in women taking hormonal therapy or oral contraceptives than in those not using these medications . The remaining five articles found no correlation between TMD and the use of exogenous hormones .

Lastly, six articles showed that low oestrogen levels and hormonal fluctuations through the menstrual cycle , sex and age , polycystic ovary syndrome46, and hyperemesis gravidarum influence signs and symptoms of TMD.

Table 7 shows an overview of the articles included and their main outcomes.

Table 7
Characteristics and main outcome of the included articles.
Reference Year Study design Subjects ( n ) Category Conclusion
Gunson et al. 2009 Retrospective cohort 27 females with ICR 1 Low circulating 17β-oestradiol makes it impossible for the natural reparative capacity of the condyle to take place in the face of local inflammatory factors
Yang and Hwang 2015 Prospective cohort 16 females with ICR 1 Lower serum levels of 17β-oestradiol in patients with preoperative ICR
Nogami et al. 2016 Retrospective cohort 25 females with TMJ OA
(8 with ACR, 17 without ACR)
1 OC was not a risk factor for condylar resorption following orthognathic surgery
Abubaker et al. 1993 In vitro 7 TMJ discs from females with TMD
15 TMJ discs from subjects without TMD
2 Presence of oestrogen receptors in the TMJ discs of both symptomatic and asymptomatic men and women
Campbell et al. 1993 In vitro 14 discs from patients with TMD
(10 female, 4 male)/breast tissue cells
2 Lack of oestrogen receptor in TMJ discs
Henry et al. 2008 In vitro 28 TMJ discs from patients with TMD
(26 female, 2 male)/breast tissue control
2 Lack of oestrogen receptor in the posterior ligament of the TMJ
Galal et al. 2008 In vitro Synovial cells from a 67-year-old female 2 Oestrogen increased expression in joint cells
Ribeiro-Dasilva et al. 2017 In vitro Monocytes from 18 females
(9 with TMD, 9 without TMD)
2 Oestrogen-induced monocytic response in TMD-derived monocytes was correlated with pain in women with TMD
Kang et al. 2007 Case–control 100 females with TMJ OA
74 females without TMD
2 ESR1 polymorphism (PX haplotype) was associated with the severity of pain in female TMJ OA patients
Ribeiro-Dasilva et al. 2009 Case–control 200 female subjects with TMD
100 female subjects without TMD
2 ESR1 polymorphism may increase the susceptibility of women to develop TMD
Kim et al. 2010 Case–control 74 with TMD (50 female, 24 male)
64 without TMD (41 female, 23 male)
2 There was no statistically significant association between ESR1 polymorphism and symptoms of TMD
Stemig et al. 2015 Case–control 42 with TMD
36 without TMD
2 The presence of polymorphism possibly modulates the ERα activity in bone and contributes to the degenerative process in the joint
Bonato et al. 2016 Cross-sectional 410 2, 3 Significant association between ESRRB polymorphisms and TMD
No association between serum oestrogen level and TMD
Nicot et al. 2016 Prospective cohort 101 subjects undergoing orthodontic and maxillofacial surgery 2 Polymorphisms of ESR1 as a risk factor for dysfunctional worsening of TMD after orthognathic surgery
Landi et al. 2004 Case–control 35 with TMD
24 without TMD
3 High serum oestrogens levels might be implicated in the pathophysiology of TMD
Landi et al. 2005 Case–control 40 with TMD (20 female, 20 male)
32 without TMD
3 High serum oestrogen levels might be implicated in the pathophysiology of TMD
Madani et al. 2013 Cross-sectional 142 females; 47 with TMD, 95 without TMD 3 Serum oestradiol level is not a risk factor for TMD
LeResche et al. 1997 Case–control 2764 females with TMD
11,056 controls
3 HRT and OC use was higher in women with TMD
Dao et al. 1998 Prospective cohort 12 females with myofascial pain
(5 using OC, 7 not using OC)
3 Pain levels in OC users may be more constant than those of non-users across the menstrual cycle
Sherman et al. 2005 Prospective cohort 18 females with TMD with normal cycle
25 females with TMD using OC
25 females without TMD with normal cycle
26 females without TMD using OC
3 Phase-related differences in the experimental pain response were not strong and were more often found for palpation pain compared with an ischemic pain task
Madani et al. 2011 RCT 7 females using OC
12 females not using OC
3 OC is not a risk factor for TMD
Goncalves et al. 2011 Case–control 14 females with DDR and using OC
14 females with DDR with normal cycle
16 females without DDR and using OC
17 females without DDR with normal cycle
3 Hormonal fluctuation and OC did not influence mastication force
Turner et al. 2011 RCT 114 females with TMD not using OC
57 females with TMD using OC
3 Pain improved more in women with a normal cycle compared to the OC user group after 1 year of treatment
Wise et al. 2000 Cross-sectional 87 postmenopausal females 3 Postmenopausal women receiving HRT reported higher levels of orofacial pain than postmenopausal women not taking HRT
Hatch et al. 2001 Cross-sectional 510 females 3 HRT does not place women at increased risk of developing TMD
Nekora-Azak et al. 2008 Cross-sectional 180 postmenopausal females 3 No association between HRT and the signs and symptoms of TMD
Lora et al. 2016 Cross-sectional 284 postmenopausal females 3 No relationship between TMD and HRT
Suenaga et al. 2001 Prospective cohort 42 females with TMD 3 Joint pain was highest in the menstrual and secretory phases; positional changes of the disc and the menstrual cycle may play a role in the degree of joint pain and inflammatory pathology of the posterior disc attachment
LeResche et al. 2003 Prospective cohort 35females with TMD using OC
35 females with TMD not using OC
21 males with TMD controls
35 females with normal cycle controls
3 TMD pain in women is highest at times of lowest oestrogen, but rapid oestrogen change may also be associated with increased pain
Vilanova et al. 2015 Prospective cohort 50 females with TMD
(25 using OC, 25 with normal cycle)
3 Hormonal fluctuations intensify pain in women with symptomatic TMD using or not using OC
Schmid-Schwap et al. 2013 Cross-sectional 502 subjects with TMD
(404 female, 98 male)
3 Female TMD patients showed increased pain and muscle tenderness on palpation as compared to males; females also showed peaks of prevalence of TMD in the age group <25 years and in the group 55–60 years
Soydan et al. 2014 Prospective cohort 100 premenopausal females
(50 with PCOS, 50 controls)
3 Higher incidence and severity of TMD with PCOS and suspected that chronic low-grade inflammation may play a part in the aetiology of the disease
Tian et al. 2017 Case–control 449 subjects with hyperemesis gravidarum
459 controls
3 Increase in reporting of TMD prior to pregnancy in women with hyperemesis gravidarum
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Dec 14, 2017 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Is oestrogen associated with mandibular condylar resorption? A systematic review
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