Evaluation of the effect of menopause on mandibular cortical and trabecular bone structure using panoramic radiographs in patients with periodontitis

Abstract

Background

Menopause and periodontitis can lead to changes in mandibular bone structure. Fractal dimension (FD) and radiomorphometric indices, which are widely are used to assess such changes.

Objective

This study aimed to evaluate mandibular trabecular bone using fractal analysis and cortical bone using radiomorphometric indices on panoramic radiographs of individuals with and without periodontitis during the perimenopausal and postmenopausal periods.

Methods

This retrospective study used panoramic radiographs from 60 females, categorized into four groups: perimenopausal and periodontally healthy (PERI-H); perimenopausal with periodontitis (PERI-P); postmenopausal and periodontally healthy (POST-H); postmenopausal with periodontitis (POST-P). Radiomorphometric indices and FD were measured bilaterally on selected condylar (F1, F6) and gonial regions (F2, F5), as well as between the first molar and second premolar teeth (F3, F4) bilaterally.

Results

In the F3 and F4 regions, the POST-P group exhibited lower FD values compared to the PERI-H group (p = 0.035, p = 0.001, respectively). In the F1 region, significantly lower FD values were observed in the POST-P group versus the PERI-H, PERI-P and POST- H groups (p = 0.017, p = 0.011 and p = 0.017, respectively), and the POST-H group showed significantly lower FD values than the PERI-H group (p = 0.011). Cortical bone classification showed that C1 was most common in the PERI-H group (66.7%), C2 in the POST-H and POST-P groups (60.0%, 66.7%, respectively), and C3 in the POST-P group (26.7%) (p = 0.004).

Conclusions

Postmenopausal females exhibited greater bone resorption in the alveolar region and the right condyle, and also showed lower FD values compared to perimenopausal females. Additionally, females with periodontitis exhibited lower fractal dimension values and increased bone porosity compared to the healthy group.

Keywords

Fractal dimension analysis menopause periodontitis radiomorphometric index

1. Introduction

Periodontitis is a multifactorial inflammatory condition caused by complex interactions between subgingival pathogenic bacteria and the host's immune response, leading to periodontal tissue destruction, alveolar bone loss, and eventually tooth loss. Both environmental and genetic factors contribute to the etiopathogenesis and progression of periodontitis.¹

During menopause, women experience fluctuations in sex hormones, which affect the severity of periodontal diseases.^2–4 Estrogen plays a protective role by reducing the production of inflammatory cytokines involved in osteoclastic activation. Consequently, estrogen deficiency associated with menopause leads to alveolar bone loss, gingival inflammation, and increased loss of clinical attachment.⁵

Estrogen exerts its effects on osteocytes, osteoblasts, immune cells, and other cell types by binding to estrogen receptors (ER) expressed on these cells.^6,7 In addition to bone, ER are also present in the gingiva, oral mucosa, and salivary glands. As such, hormonal fluctuations may influence the oral environment and exacerbate the inflammatory response.⁸ Estrogen deficiency induces upregulation of immune cells and osteoclasts, leading to increased production of bone-resorbing cytokines. This elevation in inflammatory cytokines and other mediators can affect not only systemic bone remodeling but also impair local tissue responses to periodontal disease.⁵

The World Health Organization (WHO) defines natural menopause as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity for at least 12 months.⁹ The menopausal period is divided into four stages: premenopause, perimenopause, menopause and postmenopause. Premenopause refers to the time period between menarche and the onset of menopause. Perimenopause is when initial symptoms appear, and irregular menstrual cycles begin; menopause is marks the timepoint at which menstruation ceases permanently, typically identified by the final spontaneous menstrual bleeding; and postmenopause is defined as the period beginning one year after menopause.^10,11

To the best of the authors’ knowledge, no studies in the literature have reported on the impact of periodontal health on mandibular cortical and trabecular bone in perimenopausal and postmenopausal females. Cortical bone constitutes the outer layer of the mandible, also known as the cortex, while trabecular bone is the porous and spongy bone type located within the cortical bone.¹² Differences in trabecular bone are quantified using the fractal analysis (FA) method, while radiomorphometric indices were utilized to evaluate changes in cortical bone. Periodontitis is not considered to have a direct effect on cortical bone. Instead, it is thought that, in addition to the effects of menopausal changes on trabecular and cortical bone, the presence of periodontitis may contribute to the changes of cortical bone in the inflammatory process.

Fractal analysis is a mathematical method used to characterize the degree of complexity of irregular patterns or structures found in nature, such as bone, which is quantitatively expressed by the fractal dimension (FD).¹³ This method allows for the assessment of a bone's three-dimensional (3D) structure using two-dimensional images.^14,15 An increase in the FD value indicates greater structural complexity; a higher FD signifies a denser bone structure with reduced porosity, while a lower FD indicates increased porosity.¹⁶ Although dual-energy X-ray absorptiometry (DXA) is considered the gold standard for assessing bone mineral density (BMD) in cases of osteopenia and osteoporosis, it involves additional radiation exposure for patients.¹⁷ In this study, we employed the FA method because of its advantages, including the elimination of the need for additional radiation when measuring BMD and its cost-effectiveness.

The current study aimed to identify differences in mandibular trabecular and cortical bone through various assessments using panoramic radiographs of both perimenopausal and postmenopausal females, with or without periodontitis.

The null hypothesis of the study posited that the stages of menopause and periodontal health status are not associated with changes in mandibular cortical and trabecular bone structure.

2. Materials and methods

This study was conducted following the ethical principles laid out in the Declaration of Helsinki. Approval for the study was obtained from the Institutional Review Board of Sivas Cumhuriyet University (No. 2021-10/08).

In this retrospective study, archived hormone test results for follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, and E2 (estradiol), along with periodontal examination records of female patients who presented to the periodontology clinic between 2019 and 2020 were used.

An FSH level exceeding 40 IU/L aids in the diagnosis of menopause. While E2 levels fluctuate considerably during perimenopause, they consistently remain below 30 pg/mL one year after menopause. Prior to menopause, LH levels are assessed on Day 3 of the menstrual cycle, typically ranging from 5 to 20 mIU/mL. During the perimenopausal period, LH levels increase, but do so at a delayed rate compared to FSH levels. Progesterone levels are typically 1 ng/mL or lower in postmenopausal women.^18,19

Biochemical hormone test results were examined in light of the aforementioned data. Patients who reported having irregular menstrual cycles in their medical history but were not yet menopausal were categorized as “perimenopausal,” while those who had been menopausal for more than one year were classified as “postmenopausal”. Perimenopausal and postmenopausal women with a close age distribution constituted the study group. Among the patients evaluated in the postmenopausal group, the duration since the onset of menopause ranged between 2 and 4 years.

The menopause stage and periodontal status of the same patients were evaluated and noted by a periodontist with 21 years of experience. Patients with a probing pocket depth of no more than 3 mm and oral bleeding scores below 10% were categorized as “periodontally healthy”. Only patients with Stage III, Grade B periodontitis were included in the “periodontitis group”. Accordingly, these patients exhibited a probing pocket depth of ≥4 mm and <7 mm in at least two non-adjacent teeth, along with bleeding on probing, signs of inflammation, and bone loss extending to the middle or apical third of the root (Stage III, Grade B periodontitis) were included in the study.²⁰

Individuals included in the study were required to have no systemic diseases other than menopause-related osteoporosis (such as diabetes mellitus, rheumatoid arthritis, ankylosing spondylitis), no use of medications (especially bisphosphonates), and no jaw pathology, such as cysts or tumors. Pregnant and breastfeeding women were excluded from the study. Only panoramic radiographs that were free of artifacts or positioning errors and exhibited optimal image quality for fractal analysis and radiomorphometric index measurements—allowing for clear visualization of the mental foramen—were included in the study. Two radiographs with positioning errors and where the mental foramen could not be visualized were excluded from the evaluation.

The sample size required for the study was calculated using G*Power 3.9.1.4. (Heinrich Heine Universität, Düsseldorf Germany). Power analysis showed that a total of 60 individuals would be required based on α = 0.05, β = 0.20, 1-β = 0.80, with an effect size (f) of 0.444. The estimated power was 0.8050075.²¹ Accordingly, groups were established with 15 individuals each, and fractal analysis was performed along with the calculation of radiomorphometric indices on the panoramic radiographs of these individuals:

–
15 perimenopausal, periodontally healthy individuals (PERI-H),
–
15 perimenopausal individuals with periodontitis (PERI-P),
–
15 postmenopausal individuals periodontally healthy individuals (POST-H),
–
15 postmenopausal individuals with periodontitis (POST-P).

2.1. Display features

All radiographs intended for fractal analysis were reviewed by a dentomaxillofacial radiologist using a 64-bit LCD display (Lenovo IdeaPad Z500 Intel Core i5) with a 15.6-inch LED backlight and a resolution of 1366 × 768 pixels. The examination took place in a dimly lit, quiet room to ensure optimal visibility.

2.2. Image processing

2.2.1. Fractal analysis

Panoramic radiographs with a resolution of 1536 × 2976 pixels were used for this study. FD analysis was conducted using ImageJ 1.53k software, bundled with 64-bit Java (available at https://imagej.nih.gov). The images with anonymized patient identifiers were saved in the JPEG format. The box counting method proposed by White and Rudolph²² was used for FD estimation.

2.2.2. Region of interest (ROI) selection

A total of six ROIs were selected on the panoramic radiographs, excluding the lamina dura and cortical margins:

Right and left condylar regions (60 × 60 pixels) (F1, F6),

Right and left gonial regions (60 × 60 pixels) (F2, F5),

The region between the first molar and second premolar teeth bilaterally (20 × 100 pixels) (F3, F4) (Figure 1).

Figure 1.

Selection of the specified ROIs in the mandible on the panoramic radiograph. (F1-6, condylar region; F2-5, gonial region; F3-4, region between second premolar and first molar).

Initially, the ROIs were cropped and duplicated (Figure 2). The image was blurred using a Gaussian filter (σ = 35 pixels) to eliminate brightness variations caused by soft tissues (Figure 2(a)). The blurred image was then subtracted from the original image (Figure 2(b)). Next, the image was converted to an 128-level grayscale (Figure 2(c)) to differentiate the trabecular bone from the surrounding bone marrow. The “Threshold” option was used to create a binary (black-and-white) image (Figure 2(d)). The “Erode” tool was applied to reduce noise (Figure 2(e)). The “Dilate” step expanded the relevant areas for improved visibility (Figure 2(f)). Color inversion was performed using the “Invert” tool (black to white, and vice versa) to highlight the outlines of the trabecular bone (Figure 2(g)). The binary image was then reduced to a one-pixel-wide spine at the “Skeletonize” step (Figure 2(h)).

Figure 2.

Image (a) blurring, (b) subtraction, (c) c conversion to grayscale, (d) binarization, (e) erosion, (f) dilation, (g) color inversion, (h) skeletonization.

The FD was calculated for these outlines using the “Analyze” tool. Next, boxes of 2, 3, 4, 6, 8, 12, 16, 32 and 64 pixels were overlaid on the image, and the number of boxes covering the trabecular structures, along with the total number of boxes, was counted using the software's box counting function. A logarithmic graph of these values was plotted, and the slope of the best-fitting line passing through the points provided the FD value.

2.3. Radiomorphometric analysis

Changes in the mandibular cortical bone were assessed using radiomorphometric indices. The Mandibular Cortical Index (MCI) was classified into three groups, as described by Klemetti et al.²³ in 1994:

C1: Indicates a normal cortex, where the endosteal margin of the cortex appears even on both sides, showing no porosity.

C2: Indicates mild-to-moderate cortical erosion, characterized by the formation of resorption cavities and endosteal cortical residues (1 to 3 layers) on one or both sides.

C3: Indicates severe erosion of the cortex, where the endosteal margin is visibly porous.

The morphology of the mandibular cortical bone distal to the mental foramen was examined bilaterally (Figure 3).

Figure 3.

Examples of the types of the mandibular cortex: (a) MCI C1, (b) MCI C2, (c) MCI C3. *C1: PERI-H group; C2: POST-H group; C3: POST-P group.

Mental Index (MI): The cortical bone thickness at the point where the line passing through the center of the mental foramen intersects perpendicularly with the line running parallel to the long axis of the mandible and tangent to its inferior margin. The mental foramen was evaluated using the technique described by Ledgerton et al.²⁴

Panoramic Mandibular Index (PMI): The ratio of the cortical thickness measured at the mental foramen to the distance between the inferior margin of the mental foramen and the inferior margin of the mandible.²⁵

The MI and PMI values calculated from panoramic radiographs bilaterally were compared among the groups (Figure 4). The PMI and MI measurements were performed using calibrated ImageJ version 1.53k software, and the images did not contain any patient information.

Figure 4.

Mental index (A), panoramic mandibular index (A/B ratio).

All radiomorphometric and FD measurements were conducted by a dentomaxillofacial radiologist with 7 years of experience. In this retrospective study, 25 randomly selected radiographs (41.6%) were re-evaluated by the same radiologist after a 15-day interval to assess intra-observer agreement.

2.4. Statistical analysis

Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY). Descriptive statistics were reported as arithmetic mean, standard deviation (SD), and frequency with percentage. When the assumptions for parametric tests were met (as verified by the Shapiro-Wilk test), one-way analysis of variance (ANOVA) was employed to compare measurements across four independent groups. Tukey's Honest Significant Difference (HSD) test (a post hoc test) was used to identify the specific group(s) responsible for any observed differences. Categorical data (the MCI values) were analyzed using the Monte Carlo Chi-square test. The Bonferroni method was applied to determine intergroup differences. Intra-class correlation coefficients (ICC) and kappa statistics were calculated to assess intra-observer agreement. The significance level was set at 0.05.

3. Results

In this study involving 60 individuals, the mean ages were as follows: 42.43 ± 2.30 years in the PERI-H group, 43.30 ± 2.73 years in the PERI-P group, 48.88 ± 1.37 years in the POST-H group, and 48.80 ± 1.26 years in the POST-P group.

Significant differences were observed in the FD values among the F1, F3 and F4 regions. In the F1 region, the lowest fractal values were observed significantly in the POST-H group, while in the F3 and F4 regions, the lowest fractal values were found in the POST-P group. (p = 0.008, p = 0.039, p = 0.001, respectively) (Table 1).

Table 1.
FD values calculated on panoramic radiographs.

N FD Mean ± SD Results

F1 PERI-H 15 1.622 ± 0.042 F = 4.39

PERI-P 15 1.569 ± 0.061 p = .008^abcd

POST-H 15 1.542 ± 0.059

POST-P 15 1.545 ± 0.099

F2 PERI-H 15 1.596 ± 0.088 F = 1.16

PERI-P 15 1.548 ± 0.125 p = .333

POST-H 15 1.527 ± 0.119

POST-P 15 1.533 ± 0.113

F3 PERI-H 15 1.334 ± 0.041 F = 2.98

PERI-P 15 1.296 ± 0.104 p = .039^e

POST-H 15 1.279 ± 0.048

POST-P 15 1.269 ± 0.041

F4 PERI-H 15 1.325 ± 0.039 F = 6.00

PERI-P 15 1.297 ± 0.034 p = .001*^f

POST-H 15 1.284 ± 0.065

POST-P 15 1.258 ± 0.032

F5 PERI-H 15 1.568 ± 0.071 F = .59

PERI-P 15 1.565 ± 0.099 p = .624

POST-H 15 1.557 ± 0.083

POST-P 15 1.524 ± 0.144

F6 PERI-H 15 1.620 ± 0.055 F = 1.60

PERI-P 15 1.575 ± 0.086 p = .199

POST-H 15 1.567 ± 0.064

POST-P 15 1.575 ± 0.083

	N	FD Mean ± SD	Results
F1	PERI-H	15	1.622 ± 0.042	F = 4.39
PERI-P	15	1.569 ± 0.061	p = .008*^abcd
POST-H	15	1.542 ± 0.059
POST-P	15	1.545 ± 0.099
F2	PERI-H	15	1.596 ± 0.088	F = 1.16
PERI-P	15	1.548 ± 0.125	p = .333
POST-H	15	1.527 ± 0.119
POST-P	15	1.533 ± 0.113
F3	PERI-H	15	1.334 ± 0.041	F = 2.98
PERI-P	15	1.296 ± 0.104	p = .039*^e
POST-H	15	1.279 ± 0.048
POST-P	15	1.269 ± 0.041
F4	PERI-H	15	1.325 ± 0.039	F = 6.00
PERI-P	15	1.297 ± 0.034	p = .001*^f
POST-H	15	1.284 ± 0.065
POST-P	15	1.258 ± 0.032
F5	PERI-H	15	1.568 ± 0.071	F = .59
PERI-P	15	1.565 ± 0.099	p = .624
POST-H	15	1.557 ± 0.083
POST-P	15	1.524 ± 0.144
F6	PERI-H	15	1.620 ± 0.055	F = 1.60
PERI-P	15	1.575 ± 0.086	p = .199
POST-H	15	1.567 ± 0.064
POST-P	15	1.575 ± 0.083

*One-way ANOVA

Post-hoc test Tukey: ^aPERI-H vs. POST-H (p = .011), ^bPERI-H vs POST-P (p = .017), ^cPERI-P vs. POST-P (p = .011), ^dPOST-H vs. POST-P (p = .017) ^ePERI-H vs. POST-P (p = .035), ^f PERI-H vs. POST-P (p = .001).

*Significant at p < .05. FD, fractal dimension; F1-6, condylar region; F2-5, gonial region; F3-4, region between second premolar and first molar.

Significant differences in FD values for the F1 region were found between the following groups: PERI-H versus POST-H (p = 0.011), PERI-H versus POST-P (p = 0.017), PERI-P versus POST-P (p = 0.011) and POST-H versus POST-P. Lower FD values were observed in the postmenopausal and periodontitis groups (p = 0.017).

In the F3 region, lower FD values were calculated in the POST-P group compared to the PERI-H group (p = 0.035).

For the F4 region, the difference in FD values between the PERI-H and POST-P groups was significant, FD values were lower in the POST-P group. (p = 0.001).

In the F2, F5 and F6 regions, no significant differences were found between the groups (p = 0.333, p = 0.624, p = 0.199, respectively).

There were no significant FD differences among the other regions and groups (p > 0.05).

When examining the radiomorphometric indices obtained from panoramic radiographs, MCI values showed a significant difference (p = 0.004). C1-type cortical bone was most frequently observed in the PERI-H group (66.7%), while C2-type bone was seen in the POST-H (60.0%) and POST-P groups (66.7%), and C3-type cortical bone was most commonly found in the POST-P group (26.7%) (p = 0.004). POST-P was the group that demonstrated a significant difference in C2- and C3-type cortical bone distribution. Pairwise comparisons revealed statistically significant differences between POST-P and the PERI-H, PERI-P, and POST-H groups. The POST-P group showed a significantly higher frequency of C2 and C3-type cortical bone distribution (p < 0.05) (Table 2).

Table 2.

MCI values evaluated on panoramic radiographs.

	MCI
	C1	C2	C3	Total n (%)	Results
PERI-H n (%)	10a (66.7%)	5a (33.3%)	0a (0.0%)	15 (100.0%)	X² = 18.17
PERI-P n (%)	8a (53.3%)	7a (46.7%)	0a (0.0%)	15 (100.0%)	p = .004*
POST-H n (%)	5a (33.3%)	9a (60.0%)	1a (6.7%)	15 (100.0%)
POST-P n (%)	1a (6.7%)	10b (66.7%)	4b (26.7%)	15 (100.0%)
Total	24 (40.0%)	31 (51.7%)	5 (8.3%)	60 (100.0%)

Chi–square test; *p < .05 denotes significance. MCI: mandibular cortical index.

a, b: Indicates statistically significant differences based on the Bonferroni correction.

Among the groups, although MI values were lower in the POST-H group on the right and in the POST-P group on the left, the differences were not significant (Right MI: p = 0.884; Left MI: p = 0.978). Similarly, the POST-P group showed the lowest PMI values on both sides, but these differences were also not statistically significant (Right PMI: p = 0.808; Left PMI: p = 0.891) (Table 3).

Table 3.

MI and PMI values measured on panoramic radiographs.

		N	Mean ± SD	Results
Right MI	PERI-H	15	5.040 ± 0.655	F = .21
	PERI-P	15	5.093 ± 0.682	p = .884
	POST-H	15	4.900 ± 0.873
	POST-P	15	4.927 ± 0.817
Right PMI	PERI-H	15	0.343 ± 0.056	F = .32
	PERI-P	15	0.336 ± 0.055	p = .808
	POST-H	15	0.343 ± 0.089
	POST-P	15	0.323 ± 0.049
Left MI	PERI-H	15	4.913 ± 0.623	F = .06
	PERI-P	15	5.00 ± 0.877	p = .978
	POST-H	15	4.893 ± 1.013
	POST-P	15	4.860 ± 1.023
Left PMI	PERI-H	15	0.339 ± 0.065	F = .20
	PERI-P	15	0.337 ± 0.059	p = .891
	POST-H	15	0.327 ± 0.067
	POST-P	15	0.324 ± 0.056

One-way ANOVA *Significant at p < .05 MI: mental index, PMI: panoramic mandibular index.

ICC between 0.80 and 0.94 indicate good reliability, and values greater than 0.95 denote excellent reliability.²⁶ Kappa coefficients are interpreted as follows: almost perfect (0.90–1), strong (0.80 −0.90), moderate (0.60–0.79), weak (0.40–0.59), minimal (0.21–0.39), and no agreement (0.00–0.20).²⁷ Intra-observer agreement was almost perfect, with all ICCs above 0.90 (p = 0.001) (Table 4).

Table 4.

Results of statistical analysis showing intraobserver agreement for 25 randomly selected individuals.

	ICC	p value
F1	0.926	.001*
F2	0.962	.001*
F3	0.900	.001*
F4	0.962	.001*
F5	0.978	.001*
F6	0.981	.001*
Right MI	0.985	.001*
Right PMI	0.973	.001*
Left MI	0.974	.001*
Left PMI	0.976	.001*
MCI	0.918	.001**

*p < .05 denotes significance. ICC: intra-class correlation coefficients; MCI: mandibular cortical index, MI: mental index, PMI: panoramic mandibular index. **Kappa statistics were conducted for MCI values.

4. Discussion

The findings of the study led to the rejection of the null hypothesis. Hormonal changes associated with menopause can affect dental and periodontal health.^28,29 Fluctuations in the levels of sex steroid hormones, particularly estrogen and progesterone, can result in alterations in vascular permeability, inflammatory mediators, and the growth and differentiation of fibroblasts. Estrogen receptors are found on periodontal tissue cells, including fibroblasts and osteoblasts.^30–32 Moreover, variations in estrogen levels can affect saliva secretion and viscosity, which in turn may heighten the risk of caries and periodontal disease.^28,29,33

In the present study examining the impact of menopause on the mandible in relation to periodontal disease, individuals in the POST-P group exhibited significantly lower FD values in the F3 and F4 regions compared to the PERI-H group (p = 0.035, p = 0.001, respectively). A decrease in BMD was observed with increasing duration of menopause and severity of periodontal disease, along with potential widening of the trabecular structure. While it remains unclear whether the observed alveolar bone loss is primarily due to menopause or periodontitis, it can be inferred that the coexistence of both conditions may exacerbate bone resorption. Moreover, it is likely that the effects of osteoporosis become more pronounced during the postmenopausal period. Additionally, some radiographs analyzed in this study revealed loss of mandibular second premolar and/or first molar teeth, potentially attributable to periodontal problems in the alveolar region. The exact time of tooth loss is unknown; therefore, it is not possible to determine how long ago the bone tissue formed as part of the healing process of the tooth alveolus. The resorption of the surrounding alveolar bone in tooth extraction sites may also have contributed to the lower FD values observed in these regions.

A potential association between osteoporosis and periodontitis in postmenopausal women has been described in several studies, suggesting that postmenopausal women may be at an increased risk of developing more frequent and severe periodontal disease.^34,35 In a 2017 study by Brasil et al.³⁶ involving ovariectomized rats, estrogen deficiency was found to significantly increase weight gain and the size of apical periodontitis lesions. In 2019, Thanakun et al.¹⁵ conducted FA on panoramic radiographs of premenopausal and postmenopausal females, selecting ROIs of 51 × 51 pixels between the apical roots of the first and second premolars. In the study, which utilized the ImageJ software (version 1.49a; National Institutes of Health, Bethesda, MD, USA), no significant difference in fractal dimension (FD) values was found between the groups. Notably, the mean age difference between the groups in the study was approximately 12 years.¹⁵ Additionally, the selection of ROIs from the apical areas rather than interdental spaces, along with the presence of the mental foramen between the teeth, may have influenced their findings. In our study, to mitigate the confounding effect of the mental foramen, we selected ROIs of 20 × 100 pixels between the teeth and observed the lowest FD values in the POST-P group bilaterally. Moreover, our study simultaneously evaluated the condylar and gonial regions along with the alveolar regions.

While several studies have reported significant differences in condylar BMD between healthy and osteoporotic patients, there are mixed results from other studies regarding the correlation between mandibular FD and skeletal BMD.^37–39 In the current study, a more porous bone structure was observed in the F1 (right condyle) region of postmenopausal females compared to their perimenopausal counterparts. This finding suggests an increase in osteoporotic activity in the condylar region during the postmenopausal period. However, the retrospective nature of the study is a limitation as it did not investigate the presence of temporomandibular joint problems or bruxism. The low FD results observed exclusively in the right condyle may indicate unilateral chewing habits among those individuals. Furthermore, during the perimenopausal period, due to all possible hormonal changes, increases in BMD may be observed in the mandibular condylar region as a result of increased tension and masticatory activity. The gonial region is also affected by bruxism, with lower gonial FD values reported in bruxists compared to the general population.¹⁴ The lack of a significant difference in the gonial FD values among the groups in our study warrants further investigation, particularly through studies comparing perimenopausal bruxists. Chewing habits associated with tooth loss may also have contributed to these outcomes. Although the patients’ body weights are unknown, they are considered a potential factor that could influence BMD.

As suggested by previous studies, the MCI can be used as a reliable screening tool for identifying postmenopausal females with low BMD who are at risk for osteoporosis.^37,40–42 In the current study analyzing radiomorphometric indices, significant differences in MCI values were observed among the groups. C1 was most prevalent in the PERI-H group, while C2 was predominant in the POST-H and POST-P groups, and C3 was most common in the POST-P group. This finding indicates the presence of increased bone resorption in the mandibular cortex among postmenopausal women, possibly due to decreased estrogen levels. Since periodontitis primarily affects the periodontium, its effect on the mandibular cortical structure is not expected. Previous research has shown that cortical erosion (C2 or C3) associated with osteopenia may reflect reduced BMD.³ Similarly, Thanakun et al.¹⁵ reported greater erosion in the mandibular cortex of postmenopausal women compared to premenopausal women using panoramic radiographs (p < 0.001).

The relation between PMI and BMD remains controversial.³⁷ In the present study, PMI (mean value: 0.3) was not significantly different among the groups. A meta-analysis and systematic review by Calciolari et al.³ identified a PMI cutoff value of 0.3 as the most accurate index for screening individuals for low BMD. Furthermore, Thanakun et al.¹⁵ reported a mean PMI value of 0.2, and did not observe a significant difference between perimenopausal and postmenopausal groups, which is in line with our findings.¹⁵ The literature presents mixed findings regarding the MI.³ In the current study, mandibular cortical width (MCW) was found to be lower in postmenopausal females compared to perimenopausal females (4 to 5 mm), albeit non-significantly. Taguchi et al.⁴³ suggested that an MCW less than 3 mm may serve as a useful threshold for predicting osteopenia or osteoporosis, as well as a criterion for referring patients for BMD assessment. Another study reported that patients with an MCW greater than 4 mm have normal BMD 90% of the time, and that the MI values were lower in osteopenic or osteoporotic individuals compared to healthy controls.³ Contrastingly, Thanakun et al.¹⁵ reported lower MI values in postmenopausal women compared to premenopausal women (non-significant difference), with a mean MI of approximately 3 mm in both groups. Kinalski et al. reported in their systematic review studies that MCW is not a suitable tool for detecting BMD loss in cases of osteopenia and osteoporosis.⁴¹ In the current study, efforts were made to balance age distribution across groups, including patients in the early postmenopausal stage. As a result, osteopenia or osteoporosis might not have developed yet or could be in its early stages, which may explain the lack of significant differences in PMI and MI values among the groups. In addition, potential positioning errors, as well as the use of different X-ray devices could account for the inconsistent findings reported in different studies.

It has been demonstrated that, despite alveolar bone resorption around the mental foramen, the distance between the inferior border of the mental foramen and the lower margin of the mandible remains relatively stable in adulthood.²⁵ Therefore, it can be concluded that radiomorphometric index values are influenced to a greater extent by postmenopausal osteopenia and osteoporosis rather than periodontitis around the dental tissues.

The strengths of this study are as follows: The combined impact of menopause and periodontitis on the mandible was assessed in patients diagnosed with menopause through hormone tests, and this evaluation was performed on four groups of equal size. This is the major strength of our study. Moreover, both fractal analysis and radiomorphometric indices were simultaneously evaluated in the same patient groups. The significant findings of our study suggest that patients with low FD values could be referred for further investigation for osteoporosis, and preventive periodontal measures may be recommended in clinical practice. All radiographic measurements and periodontal assessments were conducted by a maxillofacial radiologist and a periodontist with expertise in their respective fields.

The limitations of this study include its retrospective design, which precludes the ability to establish a direct cause-effect relationship. The presence of temporomandibular joint disorders and bruxism, which may have been present in some patients, as well as tooth loss observed in the jaw regions of certain individuals, could have contributed to the reduction in BMD. Positioning errors may occur during panoramic imaging, particularly affecting MI measurements. Moreover, using periapical or 3D radiographs in a larger population and across different stages of periodontitis could yield more comprehensive results. It has been reported that the diagnostic performance results of FD in identifying osteoporosis may serve as a reliable diagnostic tool to complement BMD tests.⁴⁴ Future studies could be prospectively designed to allow comparison of fractal and radiomorphometric analysis findings with DXA results, which are considered the gold standard in the diagnosis of osteopenia and osteoporosis.¹⁷

5. Conclusion

Radiographic analysis in this study revealed increased bone resorption in the alveolar region and right condyle in postmenopausal females compared to perimenopausal females. The co-occurrence of periodontitis appears to exacerbate bone loss, with low FD values in the alveolar region emerging as potential indicators of both periodontitis and menopause. Increased porosity of the mandibular cortical bone was observed in postmenopausal females. Menopause is associated with increased porosity of the mandibular cortical bone, and in patients with anticipated reductions in bone mineral levels, maintaining periodontal health is of critical importance.

Future studies, with larger samples and more controlled variables—such as excluding individuals with temporomandibular joint disorders, bruxism, or unilateral chewing habits—are needed to validate these findings and explore the complex interplay between menopause, periodontal health, and mandibular bone structure. These studies may also include individuals with other stages (I, II, and IV) and grades (A, B, and C) of periodontitis to provide a more comprehensive understanding.

Footnotes

Acknowledgments

We thank Ziynet ÇINAR for her contributions to the statistical analysis.

Compliance with ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study. Ethics approval for the study was obtained from the Institutional Review Board of Sivas Cumhuriyet University. (Decision no. 2021-10/08).

Informed consent statement

Informed consent was obtained from all subjects involved in the study.

Author contributions

Conceptualization, İ.E. and V.B.; Methodology, İ.E. and V.B.; Software, İ.E. and V.B.; Validation, İ.E. and V.B.; Formal Analysis, İ.E. and V.B.; Investigation, İ.E. and V.B.; Resources, İ.E. and V.B.; Data Curation, İ.E. and V.B.; Writing – Original Draft Preparation, İ.E. and V.B.; Writing – Review & Editing, İ.E. and V.B.; Visualization, İ.E.; Supervision, İ.E. and V.B.; Project Administration, İ.E. and V.B.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability and materials

The datasets created and/or analyzed during the current study are not publicly available due to ethical restrictions, but are available from the corresponding author upon reasonable request.

Institutional review board statement

Both written and verbal informed consent were obtained from the patients, and approval was obtained from the Institutional Review Board of Sivas Cumhuriyet University (ID: 2021-10/08). The study was conducted in accordance with the principles laid out in the Declaration of Helsinki.

References

Kinane

Stathopoulou

Papapanou

. Periodontal diseases. Nat Rev Dis Primers 2017; 3(1): 1–14.

Mascarenhas

Gapski

Al-Shammari

, et al. Influence of sex hormones on the periodontium. J Clin Periodontol 2003; 30(8): 671–681.

Calciolari

Donos

Park

, et al. Panoramic measures for oral bone mass in detecting osteoporosis: a systematic review and meta-analysis. J Dent Res 2015; 94(3): 17S–27S.

Chandra

Sailaja

Reddy

. Estimation of tissue and crevicular fluid oxidative stress marker in premenopausal, perimenopausal and postmenopausal women with chronic periodontitis. Gerodontology 2017; 34(3): 382–389.

Jayusman

Nasruddin

Baharin

, et al. Overview on postmenopausal osteoporosis and periodontitis: the therapeutic potential of phytoestrogens against alveolar bone loss. Front Pharmacol 2023; 14: 1120457.

Bord

Horner

Beavan

, et al. Estrogen receptors α and β are differentially expressed in developing human bone. J Clin Endoc Metabolism 2001; 86(5): 2309–2314.

Cruzoé-Souza

Sasso-Cerri

Cerri

. Immunohistochemical detection of estrogen receptor β in alveolar bone cells of estradiol-treated female rats: possible direct action of estrogen on osteoclast life span. J Anat 2009; 215(6): 673–681.

Jafri

Bhardwaj

Sawai

, et al. Influence of female sex hormones on periodontium: a case series. J Nat Sci Biol Med 2015; 6(1): 146–149.

Takahashi

Johnson

. Menopause. Med Clin North Am 2015; 99(3): 521–534.

10.

Yisma

Eshetu

, et al. Prevalence and severity of menopause symptoms among perimenopausal and postmenopausal women aged 30-49 years in Gulele sub-city of Addis Ababa, Ethiopia. BMC Womens Health. 2017; 17: 24.

11.

Soares

Taylor

. Effects and management of the menopausal transition in women with depression and bipolar disorder. J Clin Psychiatry 2007; 68(9): 16–21.

12.

Littrell

. Normal anatomy. In: Marchiori

(ed.) Clinical imaging. 3rd ed. Maryland Heights, MO: Mosby, 2014, pp.266–330. DOI:10.1016/B978-0-323-08495-6.00006-3.

13.

Sánchez

Uzcátegui

. Fractals in dentistry. J Dent 2011; 39(4): 273–292.

14.

Eninanç

Yalçın Yeler

Çınar

. Investigation of mandibular fractal dimension on digital panoramic radiographs in bruxist individuals. Oral Surg Oral Med Oral Pathol Oral Radiol 2021; 131(5): 600–609.

15.

Thanakun

Pornprasertsuk-Damrongsri

Na Mahasarakham

, et al. Increased plasma osteocalcin, oral disease, and altered mandibular bone density in postmenopausal women. Int J Dent 2019; 2019: 3715127.

16.

Sanchez-Molina

Velazquez-Ameijide

Quintana

, et al. Fractal dimension and mechanical properties of human cortical bone. Med Eng Phys 2013; 35(5): 576–582.

17.

Cadarette

McIsaac

Hawker

, et al. The validity of decision rules for selecting women with primary osteoporosis for bone mineral density testing. Osteoporos Int 2004; 15: 361–366.

18.

Sanchez

Kim

, et al. Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood. Menopause 2013; 20(11): 1169–1175.

19.

O-w

Onyeanusi

Nworie

, et al. Investigation of levels of luteinizing hormone and follicular stimulating hormone among women with polycystic ovary syndrome in Abakaliki, Nigeria. IOSR-JNHS 2016; 5(4): 104–107.

20.

Papapanou

Sanz

Buduneli

, et al. Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol 2018; 89: S173–S182.

21.

Tosoni

Lurie

Cowan

, et al. Pixel intensity and fractal analyses: detecting osteoporosis in perimenopausal and postmenopausal women by using digital panoramic images. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102(2): 235–241.

22.

White

Rudolph

. Alterations of the trabecular pattern of the jaws in patients with osteoporosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 88(5): 628–635.

23.

Klemetti

Kolmakov

Kröger

. Pantomography in assessment of the osteoporosis risk group. Eur J Oral Sci 1994; 102(1): 68–72.

24.

Ledgerton

Horner

Devlin

, et al. Panoramic mandibular index as a radiomorphometric tool: an assessment of precision. Dentomaxillofac Radiol 1997; 26(2): 95–100.

25.

Benson

Prihoda

Glass

. Variations in adult cortical bone mass as measured by a panoramic mandibular index. Oral Surg Oral Med Oral Pathol 1991; 71(3): 349–356.

26.

Alpar

Spor

. Applied Statistics and validity-reliability with examples from Educational Sciences. Ankara, Turkey: Detay Publishing, 2016.

27.

McHugh

. Interrater reliability: the kappa statistic. Biochem Med 2012; 22(3): 276–282. PMID: 23092060; PMCID: PMC3900052.

28.

Leimola-Virtanen

Salo

Toikkanen

, et al. Expression of estrogen receptor (ER) in oral mucosa and salivary glands. Maturitas 2000; 36(2): 131–137.

29.

Ciesielska

Kusiak

Ossowska

, et al. Changes in the oral cavity in menopausal women-A narrative review. Int J Environ Res Public Health 2022; 19(1): 253.

30.

Suri

. Menopause and oral health. J Midlife Health 2014; 5(3): 115–120.

31.

Romandini

Shin

Romandini

, et al. Hormone-related events and periodontitis in women. J Clin Periodontol 2020; 47(4): 429–441.

32.

Scardina

Messina

. Oral microcirculation in post-menopause: a possible correlation with periodontitis. Gerodontology 2012; 29(2): e1045–e1e51.

33.

Minicucci

Pires

Vieira

, et al. Assessing the impact of menopause on salivary flow and xerostomia. Aust Dental J 2013; 58(2): 230–234.

34.

Savić Pavičin

Dumančić

Jukić

, et al. The relationship between periodontal disease, tooth loss and decreased skeletal bone mineral density in ageing women. Gerodontology 2017; 34(4): 441–445.

35.

Singh

Sharma

Siwach

, et al. Association of bone mineral density with periodontal status in postmenopausal women. J Investig Clin Dent 2014; 5(4): 275–282.

36.

Brasil

Santos

Fernandes

, et al. Influence of oestrogen deficiency on the development of apical periodontitis. Int Endod J 2017; 50(2): 161–166.

37.

Tavares

KNP

Mesquita

Amara

PTM

, et al. Predictors factors of low bone mineral density in dental panoramic radiographs. J Osteopor Phys Act 2016; 4(1): 1–5.

38.

Alkhader

Aldawoodyeh

Abdo

. Usefulness of measuring bone density of mandibular condyle in patients at risk of osteoporosis: a cone beam computed tomography study. Eur J Dent 2018; 12(3): 363–368.

39.

Azhari

Sitam

Hidajat

, et al. Analysis line strength trabeculae condyle panoramic radiograph to diagnose osteoporosis at woman post menopause (Comparison: four region of interest). Int Res Med Sci 2016; 4(4): 63–70.

40.

Pallagatti

Parnami

Sheikh

, et al. Efficacy of panoramic radiography in the detection of osteoporosis in post-menopausal women when compared to dual energy X-ray absorptiometry. Open Dent J 2017; 11: 350–359.

41.

Kinalski

Boscato

Damian

. The accuracy of panoramic radiography as a screening of bone mineral density in women: a systematic review. Dentomaxillofac Radiol 2020; 49(2): 20190149.

42.

Audhi

Salsabila

. The analysis study of diagnostic performance and accuracy of panoramic radiography to screen bone mineral density in woman: a comprehensive systematic review. IJGM 2024; 2(2): 1–20.

43.

Taguchi

Tsuda

Ohtsuka

, et al. Use of dental panoramic radiographs in identifying younger postmenopausal women with osteoporosis. Osteoporos Int 2006; 17: 387–394.

44.

Cavalcante

Silva

PGB

Carvalho

FSR

, et al. Is jaw fractal dimension a reliable biomarker for osteoporosis screening? A systematic review and meta-analysis of diagnostic test accuracy studies. Dentomaxillofac Radiol 2022 May 1; 51(4): 20210365.