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Association between osteoporosis and periodontitis

Françoise Tilotta, Marjolaine Gosset, Julia Herrou, Karine Briot, Christian Roux

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Françoise Tilotta, Marjolaine Gosset, Julia Herrou, Karine Briot, Christian Roux. Association between osteoporosis and periodontitis. Joint Bone Spine, 2025, 92, 10.1016/j.jbspin.2025.105883. hal-05105566

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Review

# Association between osteoporosis and periodontitis

Françoise Tilotta<sup>a,b,c,*</sup>, Marjolaine Gosset<sup>b,d,e</sup>, Julia Herrou<sup>a,f</sup>, Karine Briot<sup>a,f</sup>, Christian Roux<sup>a,f</sup>

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## ARTICLE INFO

**Article history:**

Accepted 26 February 2025

Available online 14 March 2025

**Keywords:**

Osteoporosis

Periodontitis

Fracture risk

Oral health

## ABSTRACT

Both osteoporosis and periodontitis are characterized by bone resorption. Osteoporosis is defined as a generalized disease of the skeleton affecting bone microarchitecture and density and conferring a predisposition to fractures, including fractures of the upper end of the femur. Periodontitis is characterized by gingival inflammation and destruction of the alveolar bone, potentially leading to tooth mobility and loss. Both these diseases are common health concerns associated with a considerable economic and societal burden worldwide. The prevention of these two diseases is therefore a real public health issue. The close association between osteoporosis and periodontitis should lead dental surgeons to refer patients with severe periodontitis to a rheumatologist for an assessment of bone density. Conversely, patients with osteoporosis should undergo regular oral check-ups to prevent tooth loss and maintain good oral health.

© 2025 The Author(s). Published by Elsevier Masson SAS on behalf of Sociótó Franóaise de Rhumatologie. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)).

## 1. Introduction

Periodontitis is a multifactorial chronic inflammatory disease associated with an imbalance of the bacterial flora known as dysbiosis [1]. It is characterized by gingival inflammation, a loss of periodontal attachment and destruction of the alveolar bone. The progressive destruction of the tooth's anchoring system can lead to tooth mobility and eventually to tooth loss.

Periodontitis has a negative impact on general health and is associated with several systemic conditions, including cardiovascular diseases, diabetes mellitus, respiratory disorders, metabolic syndrome and adverse pregnancy outcomes [2].

Osteoporosis is defined as a systemic, progressive and diffuse disease of the skeleton, characterized by a decrease in bone mass and a deterioration of the micro-architecture of the bone tissue, increasing bone fragility and therefore the risk of fracture.

Primary osteoporosis is the most common form. It is generally age-related and mostly affects women after the menopause, as the decrease in estrogen levels associated with menopause leads to bone loss [3]. Other forms of primary osteoporosis exist but are much less common.

Secondary osteoporosis occurs in several diseases, particularly hormonal diseases, such as those of the thyroid and parathyroid glands, certain tumors, or even in patients treated with drugs for breast or prostate cancer [4].

More rarely, osteoporosis may be congenital and associated with various conditions in the context of major malformative syndromes or rare diseases, such as osteogenesis imperfecta, hypophosphatasia or X-linked hypophosphatemia [5].

There is a balance between bone formation and bone resorption in the adult skeleton. Both osteoporosis and periodontitis are characterized by an imbalance in favor of bone resorption, and these two diseases have several comorbid conditions in common. Osteoporosis causes bone damage throughout the entire skeleton, whereas periodontitis causes damage specifically to the alveolar bone supporting the maxillary (upper jaw) and mandibular (lower jaw) teeth.

Severe periodontitis has a high prevalence. It is the sixth most common human disease, affecting 11% of the world's population

<footnote><sup>a</sup> Université Paris Cité, INSERM UMR 1153, AP-HP Centre, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France</footnote>

<footnote><sup>b</sup> Université Paris Cité, INSERM UMR 1333 Oral Health, 1, rue Maurice-Arnoux, 92120 Montrouge, France</footnote>

<footnote><sup>c</sup> Service de Médecine Bucco-Dentaire, AP-HP, Hôpital Louis-Mourier, 92700 Colombes, France</footnote>

<footnote><sup>d</sup> Service de Médecine Bucco-Dentaire, AP-HP, Hôpital Charles-Foix, 94200 Ivry/Seine, France</footnote>

<footnote><sup>e</sup> Laboratoire d'Excellence INFLAMEX, Paris, France</footnote>

<footnote><sup>f</sup> AP-HP Centre, Department of Rheumatology, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France</footnote>

<footnote>* Corresponding author at: Faculté de Chirurgie Dentaire, Université Paris Cité, 1, rue Maurice-Arnoux, 92120 Montrouge, France.</footnote>

<footnote>E-mail addresses: francoise.tilotta-lazaroo@aphp.fr (F. Tilotta), marjolaine.gosset@u-paris.fr (M. Gosset), julia.herrou@aphp.fr (J. Herrou), karine.briot@aphp.fr (K. Briot), christian.roux@aphp.fr (C. Roux).</footnote>
<table><caption>**Table 1**
Articles selected for the narrative overview.</caption><thead><tr><th rowspan="2">Study</th><th colspan="3">Studied population</th><th rowspan="2">Periodontitis diagnosis</th><th rowspan="2">Osteoporosis diagnosis</th><th rowspan="2">Association periodontitis/OP</th><th rowspan="2">Authors</th></tr><tr><th>Number</th><th>Gender</th><th>Age (years)</th></tr></thead><tbody><tr><td>Choi [8]</td><td>8884<br>4580</td><td>M<br>F</td><td>+30</td><td>K05.3-K05.6 (ICD10)</td><td>BMD<br>M80-M82<br>(ICD10)</td><td>Association periodontitis/OP, especially in women over 50</td><td>DDS and MD</td></tr><tr><td>Park [9]</td><td>37,159<br>(5396 post-menopausal)</td><td>F</td><td>40-69</td><td>K05.2-K05.6 (ICD10)</td><td>Diagnosis by department of obstetrics and gynecology<br>M80-M82<br>(ICD10)</td><td>Association periodontitis/menopause</td><td>DDS</td></tr><tr><td>Chou [10]</td><td>4742<br>2556</td><td>F<br>M</td><td>40-44</td><td>CPI</td><td>BMD</td><td>Association periodontitis/OP</td><td>DDS and MD</td></tr><tr><td>Tak [11]</td><td>3111<br>2272</td><td>F<br>M</td><td>+50</td><td>CAL</td><td>BMD</td><td>Association CAL/OP</td><td>DDS and MD</td></tr><tr><td>Al Habashneh [12]</td><td>400</td><td>F</td><td>50-75</td><td>CAL,PD,GI,CI<br>Retroalveolar and bitewing radiographs<br>CAL,PD,BOP<br>Retroalveolar radiographs</td><td>BMD</td><td>Association periodontitis/OP</td><td>DDS and MD</td></tr><tr><td>Payne [13]</td><td>38 post-menopausal</td><td>F</td><td>Mean age<br>53,9 (OP)<br>52,4 (normal BMD)</td><td>CAL,PD,BOP,PI</td><td>BMD</td><td>Association periodontitis/OP</td><td>DDS and MD</td></tr><tr><td>Gil-Montoya [14]</td><td>173</td><td>F</td><td>45-72</td><td>CAL,PD,BOP,PI</td><td>BMD</td><td>Association CAL/decreased BMD</td><td>DDS and MD</td></tr><tr><td>Tezal [15]</td><td>70 post-menopausal</td><td>F</td><td>51-78</td><td>CAL,PB,BOPCI,PI<br>Retroalveolar radiographs</td><td>BMD</td><td>Association periodontitis/OP</td><td>DDS and MD</td></tr><tr><td>Kalinowski [16]</td><td>270<br>152</td><td>F<br>M</td><td>40-89</td><td>Panoramic radiographs</td><td>BMD</td><td>Association MCI/OP</td><td>DDS and MD</td></tr><tr><td>Passos-Soares [17]</td><td>492 post-menopausal</td><td>F</td><td>+50</td><td>PD,CAL,BOP, gingival recession</td><td>BMD</td><td>Association periodontitis/OP treatment</td><td>DDS and MD</td></tr><tr><td>Ayed [18]</td><td>300 post-menopausal</td><td>F</td><td>50-70</td><td>GI,CAL,PI,PD<br>Panoramic radiographs</td><td>BMD</td><td>Association periodontitis/OP</td><td>DDS</td></tr></tbody></table>

OP: Osteoporosis; BMD: Bone Mineral Density; ICD10: 2004 International Classification of Disease 10th; CPI: Community Periodontal Index (WHO, 1997); CAL: Clinical Attachment Loss; PD: Probing depth; CI: Calculus Index; GI: Gingival Index; BOP: Bleeding on Probing; MCI: Mandibular Cortical Index; PI Plaque Index.

[6]. Osteoporosis has a worldwide prevalence of 18%, reaching 23% in women [7]. The treatment and consequences of osteoporosis and periodontitis are the cause of considerable public health expenditure. Understanding the relationships between these two diseases and the means of preventing them is, therefore, of the utmost importance and constitutes a major public health challenge.

These two diseases have multifactorial etiologies, with different pathogenic factors but common systemic risk factors and the same pro-inflammatory factors underlying bone resorption. This narrative overview aims to provide an update on what is known about the relationship between osteoporosis and periodontitis. We selected articles and accepted preprints in English indexed in PubMed (MEDLINE) and supported by other research in the Web of Science (ISI) or Google Scholar databases to ensure that we did not miss important papers. The search terms used were "Osteoporosis", "Periodontitis", "Mandibular bone", "Bone mineral density", "Alveolar bone resorption", "Periodontal disease" and "Menopause". All abstracts or articles published over the last 24 years (from January 2000 until September 2024) were retrieved if directly available, and selected observational studies, clinical trials, and systematic reviews with high-quality methodology were reviewed (see the inclusion criteria). Articles that simply mentioned the abovementioned themes without in-depth analyses were excluded (Table 1).

## 2. Periodontitis

Periodontitis is a chronic inflammatory disease characterized by the progressive destruction of the apparatus responsible for

supporting the tooth. It manifests as gum inflammation, clinical attachment loss (CAL-measured, in mm, as the distance from the cemento-enamel junction to the gingival margin), gum recession, alveolar bone resorption, tooth mobility, halitosis and periodontal pockets [19] (Fig. 1). Periodontitis is responsible for a sizeable proportion of cases of edentulism [20], which must be compensated with removable or implant-supported prostheses.

Eke et al. described the prevalence of periodontitis according to different diagnostic criteria in a population of 10,683 dentate adults aged 30 years and older from the US, in the latest National Health and Nutrition Examination Survey 2009–2014 [21]. Periodontitis was present in 42% of dentate American adults aged 30 years or older (severe in 7.8%) [21].

The prevalence of periodontal diseases and susceptibility to these diseases increase with age. About 4.1% of US adults aged 30–44 years have severe periodontitis, but the prevalence of this condition doubles to reach 10.4% in the 45–64 years age group, and then doubles again to reach 9% in the group of adults aged 65 years and older [21].

The 2017 Workshop of the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) developed a new international classification of periodontal and peri-implant diseases and conditions [22]. The diagnosis of periodontitis involves staging and grading [22]. Staging depends on disease severity (stage I: initial periodontitis; stage II: moderate periodontitis; stage III: severe periodontitis with a potential for additional tooth loss; stage IV: advanced periodontitis with extensive tooth loss and potential for a loss of dentition) [1,19] (Figs. 2–4). Grading (A, slow; B, moderate; C, rapid) [1,19] corresponds to the risk of progression of the diseases and includes an assessment of
<figure><img src="image_7.png" /><figcaption>**Fig. 1.** Comparison between a healthy periodontium (left) and periodontitis (right). Bacteria penetrate the gingival-dental sulcus, trigger gingiva inflammation, causing clinical attachment loss and alveolar bone resorption.</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>**Fig. 2.** Anterior mandibular region. Periodontitis stage II. Clinical view: CAL = 3 mm (yellow arrow). Bone loss of about 20% on X ray (white arrow). No periodontitis-related tooth loss.</figcaption></figure>

risk factors (smoking, diabetes) and history of periodontal destruction.

### 3. Osteoporosis

Osteoporosis is a multifactorial disorder characterized by a low bone mass and enhanced skeletal fragility. Changes in local and systemic growth factors are responsible for uncoupling bone formation and bone resorption.

The SCOPE 2021 (Scorecard for Osteoporosis in Europe) project collected demographic and economic data for the mapping of

<figure><img src="image_9.png" /><figcaption>**Fig. 3.** Anterior mandibular region. Periodontitis stage III. Clinical view: CAL > 5 mm (yellow arrow). Bone loss on X ray > 50% (white arrow). Tooth loss due to periodontitis < 4 mm.</figcaption></figure>

osteoporosis and its management in the 27 member countries of the European Union plus Switzerland and the United Kingdom. This study showed that osteoporosis affected 32 million people in Europe in 2019 — 25.5 million women and 6.5 million men — with a prevalence of 22.1% in women and 6.6% in men over the age of 50 years [23].
<figure><img src="image_10.png" /><figcaption>**Fig. 4.** Anterior mandibular region. Periodontitis stage IV. Clinical view: CAL > 5 mm (yellow arrow). Bone loss on X ray > 50% (white arrow). Tooth loss due to periodontitis > 5 mm.</figcaption></figure>

The economic cost of osteoporosis is tending to increase, due to the aging of the population and the risk of fractures associated with this condition. The global cost associated with osteoporotic fractures in Europe was estimated at 56,930 million Euros in 2019 [23]. Due to this high prevalence, the prevention and screening of osteoporosis, and the identification of patients at high risk of fracture are major public health issues.

## 4. Pathogenesis and the emerging role of the oral and gut microbiota connecting periodontitis and osteoporosis

Periodontitis is an inflammatory disease with abacterial etiology. The process begins within dental plaque, which results from the accumulation of a biofilm consisting of several hundred, mostly commensal species of supragingival bacteria. As it matures, this biofilm develops in a subgingival direction. Socransky et al. showed that certain bacterial associations within the oral microbiota promote the transition from periodontal health to periodontitis by potentiating the pathogenic effect of certain bacteria [24]. These authors defined the Socransky complexes, including the red complex associated with advanced periodontal lesions and composed of *Porphyromonas gingivalis*, *Tannerella forsythia* and *Treponema denticola*.

According to recent advances, periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation [25]. Dysbiosis leads to inflammation, which in turn fuels the growth of dysbiotic bacterial communities, perpetuating the disease. Within this concept of the disease, *Porphyromonas gingivalis* is strongly associated with periodontitis. This bacterium disrupts the delicate balance between the various members of the oral microbial community, promoting dysbiosis [25]. The host displays an immuno-inflammatory response involving the production of high levels of pro-inflammatory cytokines (interleukins IL-1β, IL-6, IL-8 and tumor necrosis factor alpha TNF-α), prostaglandin E2 and matrix metalloproteinases (MMP-

2, MMP-3, MMP-8 and MMP-9), which leads to tissue destruction [21,26]. Once the epithelial and conjunctival attachment has broken down, tissue destruction leads to the formation of periodontal pockets and resorption of the alveolar bone. This resorption is mediated by an increase in the expression of the receptor activator of nuclear factor kappa B ligand (RANKL) by immune cells (mostly T lymphocytes) and resident periodontal cells, promoting osteoclastogenesis. These inflammatory mediators are also involved in uncoupling osteoclastosis and osteogenesis, reducing bone apposition and unbalancing bone remodeling [27].

Osteoporosis and periodontitis share a common mechanism of action, involving prostaglandins and proinflammatory cytokines [8]. Other inflammatory mechanisms dysregulated during periodontitis, such as complement protein C3 stimulation, cellular senescence and neutrophil oxidative burst [28], may also be involved in the deregulation of bone metabolism during osteoporosis. The control of inflammation therefore plays a key role in periodontitis treatment, as it influences both dysbiosis and disease progression. Gram-positive periodontal bacteria are saccharolytic; they survive by consuming the protein debris produced by periodontal tissue destruction. The inflammation associated with this destruction promotes dysbiosis and the survival of pathogenic bacteria [29].

The finding that the composition of the oral bacterial community changes during dysbiosis has led to new hypotheses concerning the mechanisms underlying osteoporosis [30]. Chronic bacteremia has been described in patients with periodontitis, together with changes in the gut microbiota due to bacterial ingestion in these patients [31]. Recent studies have, therefore, suggested that dysbiosis of the oral microbiota may alter the composition of the gut microbiota in terms of the relative abundance or diversity of different species, thereby favoring the development of various gut diseases [32]. Indeed, in a recent clinical study, the abundance of several taxa, including Bacteroides, *Faecalibacterium*, *Fusobacterium*, and *Lachnospiraceae*, was found to be higher in the fecal samples of patients with periodontitis than in those of healthy controls [33]. The association between intestinal dysbiosis and osteoporosis has been studied. Xu et al. recently reported a change in the composition of the intestinal microbiota in patients with osteoporosis, with an increase in the total number of intestinal bacteria, and a predominance of Bacteroidetes [34]. The authors, thus, demonstrated the existence of an intestinal microbiota associated with osteoporosis composed of members of the Bacteroidetes, *Prevotellaceae* and *Ruminococcaceae*, and of the genera *Faecalibacterium* and *Dialister*. In addition, Das et al. found that the levels of *Actinomyces*, *Eggerthella* and *Clostridium* cluster XIVa were higher in the gut microbiota of osteoporosis patients than in controls [35].

Dalix et al. recently demonstrated a strong association between periodontitis and rheumatoid arthritis, another inflammatory disease characterized by bone resorption. They demonstrated a key role for *Porphyromonas gingivalis* in triggering episodes of rheumatoid arthritis, particularly in its early stages [36].

The intestinal dysbiosis observed in patients with osteoporosis has been shown to alter the absorption of calcium, phosphate and magnesium during bone metabolism and to interfere with the immune system through the production of circulating pro-inflammatory and osteoclastogenic cytokines, which may control bone resorption under inflammatory conditions [30]. This dysbiosis also alters the synthesis of serotonin and other neurotransmitters involved in bone metabolism [37].

In conclusion, although the direct role of oral dysbiosis in osteoporosis remains unexplored, oral dysbiosis clearly plays an indirect role in osteoporosis through its impact on the intestinal microbiota. This role of the oral and intestinal microbiota opens up new prospects for the management of periodontitis and osteoporosis. The probiotics *Lactobacillus* sp. (notably *L. reuteri*, *L. casei*, *L. rham-
<figure><img src="image_11.png" /><figcaption>**Fig. 5.** Risk factors common to osteoporosis and periodontitis. Osteoporosis and periodontitis have several risk factors in common for the onset and/or aggravation of disease, including age > 50 years, vitamin D or calcium deficiency, smoking, genetic or hormonal factors, and nutritional imbalance. Other factors are specific to only one of these two diseases.</figcaption></figure>

nosus and *L. salivarius*) and *Bifidobacterium* appear to decrease osteoclast production significantly, thereby slowing bone resorption [38].

Osteoporosis and periodontitis have a common mechanism of action involving prostaglandins and proinflammatory cytokines [8].

## 5. Shared risk factors

Both osteoporosis and periodontitis have a multifactorial etiology. Their pathogenic factors differ, but they have many risk factors favoring disease installation or aggravation in common, particularly particularly in postmenopausal women (Fig. 5).

Osteoporosis and periodontitis can affect people of all ages, but they occur most frequently in middle-aged and elderly individuals. According to Yu and Wang, increasing oxidative stress and cellular senescence with aging drive the progression of osteoporosis and the exacerbation of periodontitis [28].

Age is significantly associated with periodontitis severity [21,39], mainly due to a decrease in immune defenses with aging or a longer period of exposure to risk factors. The high prevalence of periodontitis in the elderly is exacerbated by the difficulty of oral hygiene interventions in this population.

Smoking alters the inflammatory response and is a major risk factor common to both osteoporosis and periodontitis [28,40]. The adverse effects of smoking are further potentiated by alcohol consumption [41]. Diabetes is also a major risk factor for periodontitis, increasing its prevalence and severity [42].

Vitamin D is essential for bone metabolism and immune regulation, and has possesses profound anti-inflammatory effects [43]. It plays a role in maintaining oral immunity and the integrity of the periodontium [44]. Vitamin D deficiency is a major risk factor common to both osteoporosis and periodontitis [28].

According to Huang et al, oral hygiene maintenance and education have a significant effect on the association between periodontitis and osteoporosis [45]. Other risk factors for periodontitis include obesity, low dietary calcium intake and genetic factors [46].

The mechanisms underlying the association between osteoporosis and periodontitis are both biological and environmental. Disadvantaged populations benefit from fewer preventive measures and often display unfavorable health behaviors. Furthermore,

they are more likely to have comorbid conditions rendering them more vulnerable in terms of health.

It is difficult to assess the correlation between these two diseases, and to show, through clinical studies in humans, that one is a risk factor for the other. However, questions are now being raised about whether periodontitis is a “systemic” rather than “local” disease, which would support the argument of a biological association with osteoporosis [47].

## 6. Hormonal effects

Nine hormones have been implicated in jawbone remodeling: adiponectin, angiotensin, cortisol, erythropoietin, estrogen/testosterone, insulin, parathyroid hormone and oxytocin [48]. Park et al. showed that periodontitis was significantly more frequent among postmenopausal patients than among non-menopausal patients, regardless of age [9].

Estrogens inhibit the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin IL-1, IL-4, IL-6 and IFN-γ, which participate in osteoclast maturation and play an important role in bone resorption. Estrogen also suppresses the production of receptor activator nuclear factor kappa-B (NF-κB) ligand (RANKL) and increases osteoprotegerin (OPG) production by osteoblasts and lymphocytes, thereby maintaining the RANKL/OPG ratio required for balanced bone remodeling.

Estrogen receptors are present in the cells of periodontal tissues, such as osteoblasts and fibroblasts. The decrease in estrogen concentration at menopause can lead to changes in the levels of inflammatory mediators, vascular permeability and the growth and differentiation of fibroblasts [49]. In postmenopausal women, decreases in salivation can significantly increase susceptibility to infections and affect periodontal health [50]. However, the prevalence of periodontitis in postmenopausal patients treated with hormonal replacement therapy is statistically equivalent to that in non-menopausal patients [9].

Parathyroid hormone (PTH) is a major mediator of bone remodeling and an essential regulator of calcium homeostasis. The role of PTH in alveolar resorption remains poorly understood, but recent studies have shown that the administration of this hormone decreases alveolar bone loss and sclerostin expression in osteocytes whilst increasing osteoid formation and mineralization, suggesting
that PTH attenuates alveolar bone loss by inducing bone formation [51].

## 6.1. Association of periodontitis with osteoporosis

Bone remodeling is a process that results from a balance between the activities of bone-forming osteoblasts, bone-resorbing osteoclasts and osteocytes, cells involved in regulating this balance via their mechanoreceptors. In diseases such as periodontitis and osteoporosis, this balance is upset, driving the balance towards bone resorption.

The pathogenic mechanisms of both osteoporosis and periodontitis involve cytokines. Patients with osteoporosis have high circulating levels of the pro-inflammatory cytokines IL-1, IL-6 and TNF-α, which are considered to be osteoclastogenic. These pro-inflammatory cytokines affect bone remodeling but also act locally, compromising the tissue response to periodontitis. Inflammation of the periodontium may, in turn, lead to the release of more of these pro-inflammatory cytokines into the system, with a broad impact on inflammatory diseases [52].

Wang and McCauley suggested that the mechanisms underlying both diseases probably involve inflammatory pathways [52]. Given the risk factors common to these two diseases and their similar pathophysiological mechanisms, the link between osteoporosis, a systemic bone disease, and periodontitis, a disease manifesting notably as local bone destruction, has been the subject of numerous studies.

The possible association between these two bone-damaging diseases was first considered in 1968 [53]. In cases of alveolar bone resorption, it is useful to determine whether the observed alveolar bone destruction is a local manifestation of osteoporosis or an independent process primarily dependent on the factors underlying periodontal disease.

Tissue destruction results from the immuno-inflammatory response of the host, which involves the production of large amounts of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α), prostaglandin E2 and matrix metalloproteinases (MMP-2, MMP-3, MMP-8 and MMP-9). Once the epithelial and conjunctival attachment has broken down, tissue destruction leads to the formation of periodontal pockets and the resorption of alveolar bone mediated by increases in the expression of the receptor activator of nuclear factor kappa B ligand (RANKL) by immune cells (mostly T lymphocytes) and resident periodontal cells, promoting osteoclastogenesis. These inflammatory mediators are also involved in the uncoupling of osteoclasts and osteogenesis, reducing bone apposition and unbalancing bone remodeling [27]. Other inflammatory mechanisms dysregulated during periodontitis, such as complement protein C3 stimulation, cellular senescence and the neutrophil oxidative burst [28], may also be involved in the deregulation of bone metabolism during osteoporosis

Many studies have already explored the association between osteoporosis and periodontitis through the various clinical and radiological signs of these two diseases.

# 7. Osteoporosis/Periodontitis

Chou et al. looked for an association between the bone mineral density (BMD) measured by ultrasound at one calcaneus and periodontal health in participants aged 40 to 44 years [10]. The overall prevalence of periodontitis in the 7298 subjects studied was 31% (Community Periodontal Index, World Health Organization 1997); the prevalence of osteoporosis (BMD ≤ -2.5) was 2.1% (153/7298). The prevalence of periodontitis was higher in subjects with osteoporosis (39.9%) than in those without a low bone mass (29.5%).

In a study of 5383 subjects, Tak et al. found a significant association between the number of teeth remaining in the mouth and BMD measured at the lumbar spine and the upper end of the femur in men, with lower BMD values obtained in men with 10 or fewer teeth remaining in the mouth [11]. In women, an association was found between low BMD measured at the lumbar spine and a loss of clinical attachments of more than 4 mm.

## 7.1. Osteoporosis as a risk factor for periodontitis

Many authors have recognized osteoporosis as a risk factor for periodontitis and the worsening of periodontitis [34,54]. Al Habashneh et al. found that osteoporosis more than doubled the risk of periodontitis [12]. However, the mechanism by which osteoporosis increases the risk of periodontitis is not yet fully understood. Payne et al. concluded that osteoporosis was a risk factor for alveolar bone density loss in postmenopausal women with periodontitis [13]. A pooled analysis of 23 observational studies showed that osteoporosis was closely or strongly related to an increase in the risk of periodontitis in the future.

Despite being the ultimate consequence of periodontitis, tooth loss is less likely to be associated with osteoporosis, and the possible link between decreases in peripheral BMD and tooth loss remains a matter of debate. Dervis claimed that osteoporosis contributes to the loss of bone tissue supporting the teeth and even to the loss of teeth [34,55]. Gil-Montoya et al. showed that women receiving hormonal treatment for osteoporosis, together with vitamin D and calcium supplementation, had significantly less severe periodontitis than untreated women [14]. These two groups had an equivalent DMFT (sum of the number of decayed, missing due to caries and filled teeth), but the number of missing teeth was greater in the untreated group.

### 7.1.1. Periodontitis as a risk factor for osteoporosis

Huang et al. reported that severe periodontitis increases the morbidity of osteoporosis [45]. Zhang showed that the BMD of the fourth lumbar vertebra, femur and tibia was low in a rat model of periodontitis [56]. The authors suggested that the pathogens responsible for periodontitis could pass into the bloodstream and induce an inflammatory reaction promoting a decrease in BMD throughout the body.

In a study of a cohort of 13,464 people (8884 men, including 7403 with periodontitis, and 4580 women, including 3817 with periodontitis), Choi et al. showed that periodontitis was a risk factor for osteoporosis and that women with periodontitis were therefore more likely to develop osteoporosis (HR: 1.22, 95% CI:1.01–1.48) [8]. The authors found no such correlation in men.

In their study of 4258 postmenopausal women, Tagushi et al. showed that subjects with periodontal disease had significantly lower T-scores for total hip (p = 0.035) and metacarpal (p = 0.048) BMD than those without periodontal disease at baseline [57]. They also found that, during pharmacological treatment for osteoporosis, subjects with periodontal disease displayed a significantly smaller increase in total hip BMD T-score than subjects without periodontal disease (p = 0.021). Tezal et al. considered postmenopausal osteoporosis to be a risk factor for periodontal disease in postmenopausal Caucasian women and suggested that periodontitis is an early sign of osteoporosis [15].

However, going beyond this relationship to low bone density, the relationship between periodontitis and fracture risk is unknown. Only one study, by Kalinowski et al, has assessed the associations between radiological signs of periodontitis, mandibular cortical index (MCI- a qualitative index evaluating the appearance of the lower margin of the mandibular cortex on panoramic X rays) and the FRAX BMI-based probability of osteoporotic hip fracture within 10 years in patients aged 40–89 years
(270 women and 152 men) [16,58]. The authors showed that, in women, the risk of major or hip low-energy bone fracture directly due to osteoporosis increased in the presence of moderate or severe periodontitis and that this risk was significantly higher in patients with MCI stages C2 (moderate mandibular cortex erosion) and C3 (severely eroded mandibular cortex). No such association was found in male patients.

### 7.1.2. Osteoporosis/alveolar bone resorption

Based on a literature review, Koth et al. established a correlation between the osteoporosis-related decrease in peripheral BMD and the potentiation of alveolar bone resorption in patients with periodontitis [59]. These results are consistent with those of Tezal et al. showing that skeletal BMD is related to interproximal alveolar bone loss [15].

Using retroalveolar intraoral X rays, Payne et al. showed that osteoporotic women more frequently display a loss of alveolar bone height (P < 0.05) and a loss of alveolar bone crest density (P < 0.025) than women with a normal BMD [13]. These data suggest that osteoporosis and estrogen deficiency are risk factors for alveolar bone density loss in postmenopausal women with a history of periodontitis. These results are consistent with those of Jonasson et al, who showed that the thickness of the alveolar process is correlated with BMD in osteoporotic and osteopenic women [60].

## 7.2. Osteoporosis/CAL

There is a consensus that generalized bone loss in patients with low systemic BMD is associated with maxillary and mandibular alveolar bone loss, but the relationship between low peripheral BMD and CAL or periodontal pocket depth remains a matter of debate [61]. Indeed, results concerning the correlation between CAL and osteoporosis are highly variable, because different studies use different CAL reference values, despite the publication of a definition of periodontal disease following the 2017 workshop of the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP). Studies using CAL > 6 mm as a determinant of severe periodontitis report a positive association between CAL and systemic BMD [12,17].

Gil-Montoya et al. found a link between low BMD and the mean percentages of sites with CAL ≥ 4 mm and ≥ 6 mm in women over 60 years of age, regardless of smoking status, quality of oral hygiene or serum calcium and vitamin D concentrations [14]. The authors were unable to establish a similar relationship in women under 58 years of age. These results are consistent with those of Goyal et al, who reported a strong association between peripheral BMD and CAL [62].

In their systematic review, Penoni et al. reported that post-menopausal women with osteoporosis or osteopenia were more likely to have CAL than women with normal BMD [63]. Yu et al. confirmed the significant correlation between systemic bone loss and alveolar bone loss, but suggested a more moderate correlation between systemic BMD and CAL [28]. In a study of 300 post-menopausal women aged 50 to 70 years (150 with osteoporosis and 150 without osteoporosis), Ayed et al. showed that CAL was significantly worse in the presence of osteoporosis, whereas the opposite was reported for the depth of periodontal pockets [18]. They concluded that osteoporosis is a risk factor for periodontitis and plays a key role in the progression of the disease. Conversely, Hildebolt et al. found no relationship between CAL and bone density at the vertebrae or hip in postmenopausal women aged 41 to 70 years [64].

## 7.3. Osteoporosis/oral hygiene

Huang et al. argued that, in people with good oral hygiene, the sudden onset of periodontal decay may be an indicator of the risk of osteoporosis progression [45]. They demonstrated the importance of maintaining good oral hygiene for preventing the progression of osteoporosis, as oral hygiene significantly influences the association between periodontitis and osteoporosis.

# 8. Conclusion

Increasing numbers of studies are confirming the link between periodontitis and many systemic diseases. Periodontitis and osteoporosis have the same risk factors and involve similar bone resorption mechanisms. The hypothesis of a link between peripheral bone loss and mandibular bone loss has been confirmed. The structure of the mandibular trabecular and cortical bone could therefore be used as a true marker of osteoporosis. Imaging of the mandible, which is accessible, rapid and requires only low levels of radiation, might be an effective way to identify individuals in the early stages of osteoporosis.

One prospect for future research studies would involve the use of high-resolution peripheral quantitative tomography (HR-pQCT), a powerful imaging technique, to characterize the in vivo microarchitecture of peripheral sites in the human skeleton. This technology can determine the microarchitecture of the cortical (Ct) and trabecular (Tb) bones. Bone fragility is dependent not only on bone density, but also on a combination of bone geometry, the distribution of bone mass, microarchitecture, and the intrinsic material properties of bone tissue [65]. HR-pQCT can be used to identify bone microarchitecture phenotypes that can be used to improve the stratification of fracture risk based on phenotype-specific risk factors. This approach could improve our understanding of the pathophysiology of bone fragility, improving the prediction of fracture risk. Indeed, according to Van den Bergh et al, HR-pQCT assessments of bone microarchitecture have improved fracture prediction in predominantly normal or osteopenic elderly subjects over that achievable by DXA of the hip [66]. However, the added value is marginal. Van den Bergh et al. have argued that this technique requires further development, particularly for patients with a moderately low BMD but severe microstructural deterioration, who have a high risk of fracture.

## Funding

This research received no specific funding from any source in the public, commercial, or not-for-profit sectors.

## Disclosure of interest

The authors declare that they have no competing interests.

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