Influence of hypothyroidism on radiomorphometric parameters of mandibular radiograph: A cross-sectional case control study

doi:10.21203/rs.3.rs-4696793/v1

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Influence of hypothyroidism on radiomorphometric parameters of mandibular radiograph: A cross-sectional case control study

https://doi.org/10.21203/rs.3.rs-4696793/v1

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Thyroid hormones have a catabolic effect on bone mineral homeostasis. Hypothyroid patients have shown changes in bone mineral density with increased risk for osteoporosis and bone fractures. Radiomorphometric parameters on panoramic images are good indicators of bone mineral density. The aim of the study was to compare the radiomorphometric changes in dental panoramic images of patients diagnosed with hypothyroidism with age- and gender-matched control populations.

Materials and Methods

Panoramic radiographs of 47 patients diagnosed with hypothyroidism was measured for Radio morphometric indices like Mental index (MI), The inferior panoramic mandibular index (PMI), The antegonial index (AGI), Gonial Index (GI) and Mandibular cortical Index (MCI). The measurements were compared with age and gender matched healthy controls.

Results

The mean values of mental index, inferior panoramic mandibular index, and gonial index were observed in hypothyroidism than in healthy controls. However, only AGI showed statistically significant differences between cases and controls (p = 0.03).

Conclusion

Further studies with larger samples, comparing the dosage of hormone replacement therapy and hormone levels with bone changes, can provide substantial validated data

Hypothyroidism

Bone mineral density

Radiomorphometric indices

Panoramic radiographs

Osteoporosis.

Thyroid hormones have a catabolic effect on bone mineral homeostasis that results in increased bone resorption and calcium loss. Hence, thyroid gland disorders like hyperthyroidism and hypothyroidism are known to alter bone metabolism. Accelerated bone turnover and loss of bone mineral density, with increased risk of fractures has been observed in hyperthyroidism.(1–3) Thyroid-stimulating hormone also stimulates the release of Interleukin-6 (IL6), which increases osteoclastic activity.(4, 5) Patients with hyperthyroidism undergoing therapy have shown a significant increase in bone mineral density which further confirms the relationship between bone metabolism and thyroid hormones.(6) Hypothyroidism exhibit hypometabolism in the body with clinical symptoms in contrast to hyperthyroidism. Children with hypothyroidism when left untreated showed growth retardation with persistent short stature, disturbances of endochondral ossification, and delayed bone maturation.(1–3) Decreased bone mineral density was also observed in postmenopausal women after long-term therapy for hypothyroidism. (7). Vestergaard et al. noted a temporary increase in fracture risk within the first 2 years after the diagnosis of primary idiopathic hypothyroidism.(8) Yet uncertainty regarding alteration in bone metabolism in patients with hypothyroidism still exists.

Dental panoramic radiographs have been used and validated as an excellent tool for the detection of bone density in patients with osteoporosis, hyperthyroidism, and post-menopausal women. Cortical indices, such as cortical width and cortical shape on panoramic radiographs, are good indicators of bone mineral density (BMD) (9). The mandibular cortical index (MCI), panoramic mandibular index (PMI), mental index (MI), antegonial index (AGI), and gonial index (GI) have been used to quantify the quality of the mandibular bone mass and assess signs of resorption. (10–12) These indices also aid in early identification of individuals with low BMD.(13, 14) However, at present, there is a lack of information regarding the impact of hypothyroidism on bone metabolism and trabecular changes in the mandible. According to literature report on thyroid disease, it has been estimated that approximately 42 million people in India suffer from thyroid disease. (15) Compared to the United Kingdom and the United States of America, the prevalence of hypothyroid cases in India has been found to be alarmingly high, thus highlighting the importance of early and prompt diagnosis to prevent changes in bone mineral density. This study was conducted with the aim of comparing the radiomorphometric changes in dental panoramic images of patients diagnosed with hypothyroidism with age- and gender-matched control populations

Patient and control groups

It was a cross-sectional cohort study conducted from June to December 2023, after the Institutional Ethics Committee approval was obtained (IEC: 608/2022). The study population included hypothyroid patients who visited the outpatient department of Oral Medicine and Radiology between June to December. Panoramic Radiographs of patients who were known case of hypothyroidism on treatment for a minimum of 5 years and more, and who needed panoramic radiograph for their dental preassessment, and treatment planning only were selected for the study. Radiographs of patients who had systemic diseases or on any other medications like steroids, bisphosphonates etc. that could affect bone metabolism were not considered. Age and gender matched radiographs of the healthy control group were selected from the archives of the radiology department.

Image production and radiomorphometric measurements

All radiographs were obtained using a Planmeca 2-D S3 unit (Planmeca Oy, Helsinki, Finland). Radio-morphometric parameters were evaluated on panoramic radiographs using ImageJ software (version 1.8.0) (National Institutes of Health, Bethesda, MD, USA). Radio-morphometric indices measured on Panoramic Radiographs are shown in Figure 1.

1. Mental index (MI): Mandibular cortical thickness was measured on a line perpendicular to the inferior border of the mandible at the middle of the mental foramen.

2. The inferior panoramic mandibular index (PMI) was measured as the ratio of mandibular cortical thickness to the distance from the inferior border of the mandible to the inferior border of the mental foramen.

3. The antegonial index (AGI) was measured as the mandibular cortical thickness in the area defined by a straight line extending tangentially from the anterior border of the ascending ramus to the inferior border of the mandible.

4. Gonial index (GI) is measured as the thickness of inferior mandibular cortex at the bisector of the gonial angle. The gonial angle is defined as the angle between the lines tangent to the posterior border of the ramus and inferior border of the mandible.

5. Mandibular cortical index (MCI) is a qualitative classification of the inferior cortical border of the mandible posterior to the mental foramen into one of 3 types, according to Klemetti et al.

C1- The endosteal margin of the cortex is even and sharp bilaterally

C2- The mandibular endosteal margins show semilunar defects (lacunar erosion) or seem to form endosteal cortical residues (one to three layers) on one or both sides

C3- The mandibular cortical layer forms heavy endosteal residues and is porous.

All data was evaluated by two observers’ author 1 and author 2 (trained dental graduates). Before commencement of the study, 2 observers along with a trained oral and maxillofacial radiologist with more than ten years of experience in the field, analyzed 10 images and came into consensus with the various morphometric measurements. All the radiomorphometric parameters were measured by observer 1. 10% of the measurements were repeated by observer 2 on a different day to evaluate inter-observer reliability. 10% of the measurements were also repeated by observer 1 after 1 month to evaluate the intra-observer reliability. The Interobserver agreement values for each measurement ranged from 0.75 to 0.9, indicating good agreement (Table 1). Intra observer correlation coefficient was 0.93, indicating excellent reproducibility.

Table 1: Showing the correlation co-efficient of Inter-observer agreement

	Inter-observer agreement
MI	0.901
IPMI	0.893
GI	0.856
AGI	0.790

Data and statistical Analysis:

The data gathered is entered in the Microsoft excel sheet and analysed using SPSS version 20. Mean values of radiomorphometric parameters among the cases and control were analysed using independent t-test and proportions were analysed using chi-square test among the two groups. P<0.05 was considered as statistically significant among the two groups.

The sample size consisted of panoramic radiographs (OPGs) of 47 patients diagnosed with hypothyroidism and 50 OPGs of healthy controls. The mean age distribution of hypothyroid cases were 52.06 ± 15.26 years, and 50 healthy controls were 47.30 ± 14.66 years. Age and gender distribution of hypothyroid group and healthy controls is described in Table 2. and no significant difference in the age and sex between cases and controls was noted.

Table 2

Distribution of study participants in Case (HT) and Control groups according to age and gender
		Cases (N = 47)		Control (N = 45)		P Value
Age in years (Mean ± SD)		52.06 ± 15.261		47.30 ± 14.66		0.128
Gender		N	%	N	%
	Male	13	27.7	21	42.0	0.23
	Female	34	72.3	29	58.0
	Total	47	100	50	100
*P < 0.05 considered as statistically significant

The mean values of MI and IPMI AGI were lower in patients than in healthy controls. AGI values showed statistically significant differences between cases and controls (p = 0.03) (Table 3).

Table 3

Comparison of quantitative radiomorphometric indices between case and control group
	Cases		Control		P value
	Mean	SD	Mean	SD	P value
MI	3.11	0.79	3.17	0.53	0.657
IPMI	0.28	0.09	0.30	0.06	0.282
GI	1.38	0.39	1.33	0.43	0.524
AGI	3.14	0.69	3.43	0.64	0.03*

*P < 0.05 considered as statistically significant.

The distribution of MCI in the patient and control groups is shown in Table 4. A significant difference was noted between the cases and controls for MCI (p = 0.001). In the case group, 55.3% had MCI at the C1 level, followed by 38.3% at C2, and 6.4% at C1. Among the controls, most participants had MCI at the C2 (74%) and C1 levels (22%).

Table 4

Distribution of the categorical MCI data between case and control groups
		Cases		Control		P value
		N	%	N	%	0.001
MCI	C1	26	55.3	11	22.0
	C2	18	38.3	37	74.0
	C3	3	6.4	2	4.0
	Total	47	100	50	100

*P < 0.05 considered as statistically significant.

Thyroid gland disorders are caused by excessive or insufficient thyroid hormone production. (16) Insufficient thyroid hormone production is known as hypothyroidism. Iodine deficiency, Hashimoto thyroiditis, and surgical removal of the thyroid gland are some of the causes of primary hypothyroidism. It is one of the most common endocrinopathies, seen 10 times more frequently in females with an overall prevalence of 3.8–4.6%. (17). Patients with hypothyroidism are medically managed with thyroid hormone replacement therapy (HRT). HRTs have been reported to alter the bone turnover rate and increased osteoclastic activity, resulting in poor bone quality, subsequently leading to an increased risk of fracture. (16, 18). While few studies have reported about the adverse effects of hypothyroidism on the skeletal structure, there are studies that have denied the increased risk of fractures [19, 20, 9,10]. A study by Bjerkreim et al. demonstrated an altered bone turnover rate with suppressed TSH levels; however, they concluded that amount of bone changes is dependent on patient. (21).

Radiomorphometric parameters are reliable indicators of bone mineral density (BMD). Although bone changes are reported to be seen in weight bearing skeletal bones, mandible is said to be in line with other bones of the body, mainly the mandibular posterior region is highly affected by resorption. Patients with lower bone mineral density have shown lower MI in patients with osteoporosis and chronic kidney failure. (22, 23) Similarly in our study, MI was lower in patients with hypothyroidism than in healthy controls. However, no statistically significant difference was noted between the two groups. The hypothyroid cases in our study showed lower values of PMI than healthy controls. The panoramic-mandibular index is also a favourable indicator of BMD. Our results were comparable to previous studies by Yilmaz S G et al (10). A study by Dagistan and Bilge et al. showed significantly lower PMI values in men with osteoporosis (22). A lower PMI was also noted in poorly controlled Type 1 diabetes mellitus patients (24).

Several authors have associated osteoporosis with a reduction in cortical thickness in the mandibular gonial region. (25, 26) Few studies have shown that the AGI has poor reliability in identifying undetected low BMD or osteoporosis. (27, 28, 29) On the contrary, studies by Dagistan and Bilge, Abdinian et al., Mahl et al., and Dutra indicated that AI was significantly different in patients with osteoporosis than in healthy individuals (22, 23, 30). Significantly lower values of AGI were noted among patients with hypothyroidism in the study sample than among healthy controls. The Mandibular Cortical Index developed by Klemetti et al. is considered a reliable and accurate indicator for BMD determination. However, few studies stated that MCI displays negligible changes (31, 32). In the present study, we found that the maximum number of patients in the case group (hypothyroid cases) had a C1 cortical index depicting even and sharp endosteal margins without much bone resorption, whereas the maximum number of patients in the control group had a C2 cortical pattern with minor semilunar defects or lacunar erosions. Yilmaz et al. ’s study also showed no significant changes in MCI between cases and healthy controls. (14) Although our study showed significant differences in the MCI between the case and control group, the pattern of cortical index was not similar to previous studies.

A limitation of the present study is that we did not consider factors such as vitamin D deficiency, calcium deficiency, or dietary habits that can alter the mandibular bone pattern. Secondly, we could not compare hormonal levels and correlate them with the mandibular morphometric pattern. Further studies with larger samples, comparing the dosage of hormone replacement therapy and hormone levels with bone changes, can provide substantial validated data.

This study showed that the antegonial index (AGI) was significantly lower in patients with hypothyroidism than in healthy individuals. Although lower values of mental index (MI), inferior panoramic mandibular index (PMI), and gonial index (GI) were observed in hypothyroid cases, no significant changes were noted when compared to healthy controls. Future multicentric large-scale studies on several radiographs of the hypothyroid are warranted. Hyperthyroid cases, applying newer technologies such as machine learning, can help us determine whether mandibular changes can predict bone changes seen in hypothyroid patients or vice versa.

Ethics approval and consent to participate

The study was conducted after the consent from the Institutional Ethics Committee ( Kasturba Medical College and Kasturba Hospital – Institutional Ethics Committee-2) clearance was obtained. Informed consent was obtained from all the hypothyroidism patients prior to using their panoramic radiographs.

Consent for publication

Not applicable

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request

Competing interests

The authors declare that they have no competing interests

Funding

This was self-funded study with no external funding support

Authors' contributions

Conceptualization: Ananya Nair (A.N.), Isha Bhardwaj (I.B.), and Vathsala Patil (V.P.). Yogesh Chhaparwal (Y.C); Methodology: Ananya Nair (A.N.), Isha Bhardwaj (I.B.), Komal Smriti (K.S) and Deepak Singhal (D.S.).; Writing—Original Draft Preparation: Ananya Nair (A.N.), Isha Bhardwaj (I.B.), and Vathsala Patil (V.P.) Writing—Review and Editing:, Komal Smriti (K.S.).; Vathsala Patil (V.P) and Deepak Singhal (D.S.), Supervision: Shubha Chhaparwal (S.C.).; All the authors have read and agreed to the published version of the manuscript.

Acknowledgements

The authors are grateful for Oral and Maxillofacial Radiology section for all the technical assistance in procuring the samples. Authors are thankful for all the patients whose panoramic radiographs were used for this study.

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No competing interests reported.

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Influence of hypothyroidism on radiomorphometric parameters of mandibular radiograph: A cross-sectional case control study

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