The association between periodontitis and hypothyroidism: A comprehensive review

Abstract

This narrative review aimed to critically synthesize and evaluate the current evidence on the association between hypothyroidism and periodontitis, with a particular focus on elucidating the underlying pathophysiological mechanisms. A comprehensive literature search was conducted on PubMed, encompassing animal, cellular, and clinical studies. The synthesized findings indicate that hypothyroidism exacerbates periodontitis through multiple interconnected pathways, including dysregulated bone metabolism, induction of systemic osteoporosis, amplification of immune-inflammatory responses, and disruption of oral microbiome homeostasis. Furthermore, evidence suggests a potential bidirectional relationship, wherein periodontal therapy may positively influence thyroid function parameters. A key takeaway from this review is the importance of interdisciplinary collaboration between endocrinologists and dental professionals. Incorporating thyroid function evaluation into periodontal management may enhance treatment outcomes. This review concludes that although existing evidence supports a significant association, further high-quality longitudinal human studies are required to definitively establish causality and elucidate the precise underlying molecular mechanisms.

Preface

Periodontitis is a chronic inflammatory disease induced by plaque biofilm and characterized by alveolar bone resorption. Upon recognition of periodontal pathogens, the body mobilizes immune cells, including neutrophils, T lymphocytes, macrophages, and plasma cells, to infiltrate periodontal tissue. These cells release various inflammatory mediators, such as interleukin (IL) and tumor necrosis factor-α (TNF-α), which enhance osteoclast activity resulting in alveolar bone resorption. ¹ Currently, periodontitis is associated with 43 systemic diseases.^2,3

Thyroid, the largest endocrine organ in the human body, primarily secretes thyroxine (T4), small amounts of triiodothyronine (T3), and calcitonin (CT); T3 and T4 are collectively referred to as thyroid hormones (TH). The synthesis and secretion of TH are primarily regulated by the hypothalamus–pituitary axis. Thyrotropin-releasing hormone (TRH), secreted by the hypothalamus, stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH), which in turn, acts on the thyroid gland to promote the synthesis and secretion of TH. ⁴ TH binds to its specific target receptors to regulate various physiological processes. Elevated TH levels inhibit TRH production via a negative feedback mechanism. ⁵ Hypothyroidism (HT) is a systemic disease characterized by decreased synthesis and secretion of TH and a reduced metabolic rate. Diagnostic criteria for primary HT include elevated TSH levels above the normal reference range, along with decreased levels of free T3 and T4 below the population reference values. ⁶ Subclinical HT is diagnosed when TSH levels are elevated above the reference range, while free T3 and T4 levels remain within the normal limits.

This narrative review systematically examined the existing evidence on the association between HT and periodontitis and explored the underlying pathophysiological mechanisms to elucidate their relationship and provide insights for clinical management. This narrative review was conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA). ⁷ The clinical relevance of examining the relationship between HT and periodontitis lies in the high prevalence of both conditions and their significant impact on global patient quality of life. Identifying a potential link is essential for fostering interdisciplinary collaboration between endocrinology and dentistry, facilitating more holistic screening and management strategies. The novelty of this narrative review lies in its systematic integration of evidence across multiple mechanistic pathways, including bone metabolism, immune inflammation, and oral microbiome dysbiosis, to construct a comprehensive pathophysiological framework not previously emphasized in the existing literature. Based on the evidence, this narrative review synthesized current understanding to address the stated aim.

Literature search strategy

Review design

This article is presented as a narrative review. This format was chosen to facilitate a comprehensive and critical discussion of the existing literature, encompassing diverse study designs and pathophysiological mechanisms that link HT and periodontitis.

Search criteria

A focused literature search was conducted on PubMed to identify relevant English-language articles published between 2015 and 2025. The search strategy combined key terms, including “hypothyroidism,” “thyroid hormone,” “periodontitis,” “periodontal disease,” “bone metabolism,” “inflammation,” and “oral microbiome,” using Boolean operators (AND and OR).

Study selection

The inclusion criteria encompassed original research (human and animal studies), reviews, and meta-analyses that directly investigated the association or mechanistic pathways between HT and periodontitis. Seminal earlier publications were identified through citation tracking of reference lists.

Synthesis

The available evidence was synthesized narratively to present a coherent overview of the current understanding, identify existing knowledge gaps, and suggest future research directions.

Experimental evidence of the relationship between HT and periodontitis

Animal and in vitro studies

Thyroid dysfunction has a significant impact on periodontal tissue health. Numerous animal and in vitro studies have highlighted the detrimental effects of HT on oral health, as well as its negative influence on periodontal tissue repair and regeneration.

HT may contribute to the progression of periodontitis by disrupting bone metabolism. Analysis of alveolar bone quality in a rat model revealed markedly greater alveolar bone destruction in the HT group. ⁸ In an in vitro study by Zeng et al., ⁹ human periodontal ligament stem cells were isolated and cultured, demonstrating that elevated TSH levels significantly inhibited their osteogenic differentiation. This disruption resulted in an imbalance between osteoblasts and osteoclasts, intensifying bone destruction associated with periodontitis. HT may further contribute to periodontitis progression by disrupting connective tissue metabolism. Comparative analysis of the correlation between connective tissue metabolism indices and serum concentrations of TSH, T4, and T3 in rats demonstrated that TH regulate connective tissue metabolism. HT can disrupt this process, leading to the degradation of periodontal ligament tissue, ⁸ thereby exacerbating connective tissue damage associated with periodontitis. ¹⁰ Additionally, HT may promote periodontitis progression by disturbing the balance of the oral microbiome. Studies have reported that HT alters the balance of oral flora, increasing the risk and development of periodontitis. ¹¹

To date, the number of animal and in vitro studies exploring this association remains limited, highlighting that further research is needed to deepen the understanding of the relationship between HT and periodontitis.

Clinical evidence

HT increases the risk of periodontitis and may negatively affect its progression. Several studies have demonstrated a significant correlation between thyroid dysfunction and periodontitis, particularly among individuals with HT.^12,13 The incidence of moderate-to-severe periodontitis is higher in hypothyroid patients.^14,15 Furthermore, research has shown that even with TH replacement therapy, patients with HT still exhibit greater periodontal pocket depth and attachment loss than healthy individuals. ¹⁶ HT may also affect oral health by altering the composition and diversity of oral microorganisms, thereby disrupting the balance of the oral microbiome. ¹⁷ The relationship between HT and periodontitis may be mediated through immune system regulation. HT may influence the development of periodontitis through immune system modulation. Conversely, periodontitis may also affect thyroid function, and treatment has been shown to improve thyroid health.^18,19 Critically, a recent Mendelian randomization study enhanced causal inference by providing genetic evidence supporting a potential unidirectional effect of periodontitis on HT risk, with no evidence supporting the reverse pathway. ²⁰ This suggests that the observed clinical association may be partly driven by a causal link from periodontitis to thyroid dysfunction.

The above studies indicate that thyroid function significantly influences periodontal health; HT exacerbates the severity of periodontitis, while periodontal therapy may positively contribute to improving thyroid function and overall health.

Possible mechanism of HT in association with periodontitis

TH and bone metabolism

TH regulate bone remodeling by modulating osteoblast and osteoclast activity. ²¹ Under normal TH levels, bone resorption and formation remain balanced. However, when TH levels decrease, osteoblast activity diminishes, leading to a reduction in bone matrix synthesis. This results in decreased bone mineral density and an increased risk of osteoporosis. ²² Conversely, elevated TH levels enhance osteoclast activity, accelerating bone resorption. ²³ Although osteoblast viability also increases, the rate of bone resorption cannot be fully compensated, thereby increasing the risk of osteoporosis and fractures. ²⁴ Therefore, it is hypothesized that HT influences alveolar bone metabolism and contributes to periodontitis progression by affecting osteoblast and osteoclast activity.

Effect of osteoporosis induced by HT

HT-induced osteoporosis may exacerbate periodontitis progression as a systemic condition. Both osteoporosis and periodontitis are characterized by bone resorption. ²⁵ HT disrupts normal bone metabolism, creating risk factors for osteoporosis. Osteoporosis is characterized by the deterioration of bone microstructure and reduced bone mineral density, which increases fracture risk. Approximately 50% of women and 20% of men older than 50 years experience osteoporotic fractures. ²⁶ Stratified analysis of major osteoporotic fractures by sex and age revealed that hyperthyroidism is significantly associated with increased fracture risk in postmenopausal women, whereas HT is significantly associated with an elevated fracture risk in men younger than 75 years, with the risk increasing with age. ²⁷

Compared to clinical indicators, imaging-based assessments demonstrate a stronger correlation between the two conditions, revealing shared risk factors. Furthermore, both diseases themselves serve as risk factors for each other. ²⁸

HT is characterized by a state of low bone turnover rate, prolonging the bone remodeling cycle and reducing the absorption, maturation, and activity of osteocytes, thereby decreasing both bone resorption and formation over time. ²⁹ TH are essential for maintaining homeostasis and metabolism, significantly influencing bone growth, development, and mineral accumulation. Furthermore, bone tissues respond differently to TH. Studies have shown that although long bones, which are more prone to fractures, exhibit a higher risk of osteoporosis, bones in specific areas, such as the spine, have a lower risk. ³⁰ TSH not only regulates TH levels but also independently modulates bone formation and resorption. ³¹ Therefore, the impact of osteoporosis induced by HT on alveolar bone warrants further investigation.

Impact of HT on the immune system and its role in exacerbating inflammation

HT can impair the normal functioning of the immune system, reducing the activity of immune cells and weakening the body’s defense against periodontal pathogens. ³² Additionally, it may influence periodontitis progression by regulating inflammation and cytokine networks. Given that various immune cells have been shown to express TSH receptors, TSH is proposed as a potential regulator of the immune system. It promotes lymphocyte proliferation and activation, aids in the development of thymic T cells, and enhances the phagocytic activity of dendritic cells as well as the secretion of proinflammatory cytokines. ³³ Both innate and adaptive immune system cells express components involved in local TH signaling, rendering them sensitive to TH, which affects immune cell function. Studies have shown that inflammatory marker levels are significantly elevated in patients with HT, which stimulates resident cells in periodontal tissue to produce metalloproteinases, mediating connective tissue destruction and inducing osteoclast differentiation and activation, ultimately leading to periodontal tissue damage. ³⁴ The endotoxins produced by bacteria in dental plaque interact with these cytokines, triggering the release of additional cytokines, activating matrix metalloproteinases, and exacerbating periodontal destruction, thereby further intensifying the inflammatory cascade.

HT is closely associated with oxidative stress, often characterized by elevated levels of oxidative stress, increased production of free radicals, and an imbalance in the antioxidant defense mechanisms. ³⁵ This disruption contributes to periodontal tissue destruction, enhances inflammation, and accelerates periodontitis progression.

HT and its effect on oral microflora balance

Oral microflora consists of various microorganisms that inhabit the oral cavity and play a crucial role in maintaining both oral and systemic health. An imbalance in this microbiota can lead to oral diseases, including periodontitis. ¹⁷ HT disrupts the diversity of oral microorganisms, disturbing the balance of the oral microflora and influencing the progression of periodontitis. It is characterized by a significant increase in the abundance of cocci and Candida albicans, such as Staphylococcus aureus, yeast-like fungi, and Candida species, which gradually suppress the growth of beneficial microorganisms such as Lactobacillus, Bacteroides, and Bifidobacterium. ¹¹ The imbalance in oral microbiota not only exacerbates inflammation but also disrupts endocrine function, further compromising thyroid health.^36,37

Discussion

This review systematically investigated the potential association between HT and periodontitis and explored its multifaceted underlying mechanisms. By integrating existing experimental evidence from animal models, in vitro studies, and clinical observations with theoretical analysis, we propose and elaborate on a conceptual framework wherein HT promotes periodontitis progression through several interconnected pathways. These include the disruption of bone metabolism balance, induction of systemic osteoporosis, exacerbation of immune-inflammatory responses, and destabilization of oral microbiota homeostasis.

Comparison and integration with the existing literature

To contextualize the findings, we compared and integrated the key insights from this review with the existing body of literature. The principal findings of this review are consistent with and reinforce the existing body of literature. Concerning bone metabolism, our conclusions align with experimental evidence: rat models of HT exhibit more severe alveolar bone destruction, ⁸ while in vitro studies directly demonstrate that elevated TSH levels significantly inhibit the osteogenic differentiation of human periodontal ligament stem cells. ⁹ These findings support the classical theory proposed by Abe et al. ³¹ that TSH functions as a negative regulator of bone remodeling, consistent with the detailed accounts by Kim et al. ²¹ and Zhu et al. ²² regarding the crucial regulatory role of TH in skeletal homeostasis.

Beyond localized bone metabolism, the systemic skeletal implications of HT, particularly osteoporosis, provide an additional critical link to periodontitis. This review underscores that the low bone turnover state induced by HT, along with its adverse effects on systemic bone mineral density,^22,29 may represent a shared pathological basis for both conditions. This perspective is consistent with the view expressed by Wang et al. ²⁸ that osteoporosis and periodontitis exhibit overlapping risk factors and radiological correlations. Furthermore, epidemiological studies by Zhang et al. ²⁷ demonstrated significant associations between thyroid function status and fracture risk in specific demographic groups (e.g. men younger than 75 years of age).

In addition to these structural bone changes, dysregulated immune and inflammatory responses play a pivotal role in connecting HT and periodontitis. The integrated perspective is supported by the review by Wenzek et al., ³² which elucidated the complex interplay between the thyroid and immune systems. Early research by Klein ³³ demonstrated TSH receptor expression on immune cells, and their involvement in immune regulation provides a foundational basis for this interaction. The clinical observation of elevated inflammatory markers in patients with HT ³⁴ further substantiates the role of an amplified inflammatory cascade in driving periodontal tissue destruction.

Finally, shifting focus from the host’s internal response to the external microbial environment, the role of the oral microbiota represents a key interactive pathway. Dysbiosis observed in animal models of HT (e.g. increased abundance of cocci and Candida species) reported by Shcherba et al. ¹¹ provides direct evidence supporting this mechanism. These findings align with the broader theoretical framework proposed by Kleinstein et al., ³⁶ which posits that oral microbiome imbalance can influence systemic health, including endocrine function, through inflammatory networks. ³⁶

Multiple clinical cross-sectional studies have consistently reported a significant correlation between HT and an increased prevalence and severity of periodontitis, manifested as greater probing depths and clinical attachment loss.^12–14,16 Notably, residual periodontal damage has been observed even in patients receiving TH replacement therapy, ¹⁶ suggesting that HT may exert persistent detrimental effects on periodontal tissues that extend beyond mere hormonal insufficiency.

Novelty and contribution of this review

Having established a consistent association and identified plausible biological pathways through our integration of the existing literature, we now turn to the specific novel contributions and clinical relevance of this review. The relevance lies in its focus on the pathophysiological link between two highly prevalent chronic conditions—HT and periodontitis—that significantly impact patient quality of life. Understanding this relationship is clinically important for promoting interdisciplinary collaboration between endocrinology and dentistry and optimizing holistic, patient-centered management strategies. The novelty and primary contributions of this review are reflected in the following aspects:

Systematic integration of multimechanistic pathways. Unlike previous publications that primarily examined isolated mechanisms, this article is among the first to systematically organize, integrate, and compare the four core potential pathways (impaired bone metabolism, osteoporosis, immune-inflammatory dysregulation, and microbial dysbiosis) through which HT influences periodontitis. This integration constructs a comprehensive and interconnected pathophysiological network, providing a conceptual framework that facilitates a deeper understanding of the complexity and synergistic nature of this association and informs future research directions, such as multi-target therapeutic interventions.

Emphasis on the “microbiota–immune–bone axis” crosstalk. Among these interconnected pathways, the crosstalk within the microbiota–immune–bone axis is particularly noteworthy and represents a distinct focus of our synthesis. This review specifically highlights and elaborates on how oral microbiota dysbiosis in the HT state may act not merely as an independent factor but as a critical trigger or amplifier. It likely exacerbates periodontal destruction by activating local immune responses (e.g. promoting the release of proinflammatory cytokines such as IL-6 and TNF-α) ³⁴ and potentially disrupting systemic immune-endocrine homeostasis, ³⁶ thereby interacting synergistically with bone metabolism disorders (e.g. osteoblast/osteoclast imbalance) and systemic bone disease (osteoporosis). This perspective underscores the dynamic interplay within the microbiota–immune–bone axis, representing a significant advancement and valuable supplement to the existing literature.

Bridging mechanistic insights and clinical practice. The mechanistic insights presented herein naturally lead to important clinical considerations, which form the third major contribution of this work. Beyond mechanistic elaboration, this review explicitly outlines relevant clinical implications (see section “Conclusion”). It underscores the necessity of assessing thyroid function in periodontal practice and highlights the potential importance of managing systemic conditions like HT effectively to improve periodontal outcomes and long-term oral health. Furthermore, it suggests that periodontal therapy itself may beneficially influence thyroid-related parameters in patients with HT,^18,19 providing a rationale and direction for future rigorous interventional studies (e.g. evaluating the effects of periodontal therapy on thyroid function parameters and inflammatory markers in HT patients).

Limitations and future perspective

Despite the compelling associations and novel frameworks discussed above, it is crucial to acknowledge the inherent limitations of the current evidence base and this synthesis. Although our search strategy prioritized publications within the last decade to capture the most recent advancements, it also incorporated seminal earlier works identified through citation tracking to ensure a comprehensive foundation. Nonetheless, several important limitations must be noted:

Scarcity of high-quality longitudinal human studies. Evidence from prospective cohort studies and large-scale randomized controlled trials capable of establishing causality between HT and periodontitis progression remains limited. Existing clinical evidence primarily derives from cross-sectional^12,13,16,17 and case–control studies, which are inherently unable to definitively establish temporal relationships or causality. Interventional studies assessing the impact of periodontal therapy on thyroid function in patients with HT are few and typically involve small sample sizes,^18,19 necessitating validation through larger, well-designed trials.

Insufficient depth in mechanistic research. Although existing animal and in vitro studies (section “Review design”) provide valuable mechanistic insights,^8–11 their number remains limited. More profound research is required at molecular, cellular, and in vivo levels to precisely elucidate how HT modulates the function of specific immune cell subsets within periodontal tissues (e.g. macrophage polarization and T helper cell profiles), the role of key signaling pathways (e.g. receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANKL/OPG) and Wnt/β-catenin) in HT-aggravated periodontal bone destruction, and the specific mechanisms by which oral dysbiosis mediates local host immune responses and influences bone metabolism.

Heterogeneity of study populations. Included patients with HT exhibit heterogeneity (e.g. etiology (autoimmune vs. iodine deficiency vs. postsurgical), disease duration, severity, treatment adherence, and medication dosage). Similarly, patients with periodontitis vary in type (chronic vs. aggressive), severity, and activity. This heterogeneity may influence the interpretation, consistency, and generalizability of study findings.

Potential for confounding. Confounding factors such as age, sex, obesity, smoking status, and diabetes, which are known to influence thyroid function, immune status, bone metabolism, and periodontal health, may not have been fully measured or controlled for in observational studies, potentially introducing residual confounding or bias.

Inherent review limitations. As a narrative review, its conclusions are dependent on the quality and comprehensiveness of the included literature. Some relevant studies may have been inadvertently omitted during the retrieval process or may not have met the inclusion criteria.

Despite these limitations, the cumulative body of evidence strongly supports a clinically relevant association between HT and periodontitis. HT appears to promote the progression and severity of periodontitis through multiple, intertwined mechanisms. Acknowledging this association is of significant theoretical and practical value for advancing interdisciplinary care models, enhancing the comprehensive management of patients with these comorbidities, and ultimately improving their long-term prognosis. Future research addressing the identified gaps is essential to solidify these conclusions and translate them into improved clinical practice.

Conclusion

Current evidence indicates that HT may exacerbate the progression of periodontitis through interconnected mechanisms involving disrupted bone metabolism, systemic osteoporosis, immune dysfunction, and oral dysbiosis. The synergistic action of these pathways likely accelerates alveolar bone resorption, the hallmark of periodontitis. Although clinical observations support this association, future high-quality longitudinal studies are necessary to definitively establish causality and elucidate the underlying molecular pathways. Clinicians should recognize this potential link and account for systemic health factors, including thyroid function, in the management of periodontal disease. Interdisciplinary collaboration between dental and medical professionals is essential to optimize care for affected individuals.