Cone-beam computed tomography assessment of the prevalence and distribution of bone islands of the jaws in a group of chinese patients

Abstract

Background

Bone islands (BIs) are asymptomatic lesions typically identified incidentally on radiographs obtained for other reasons. The application of cone-beam computed tomography (CBCT) in oral clinics is becoming increasingly prevalent. This study aims to determine the prevalence of BIs in jaws by using CBCT, and to characterize the findings in relation to age, sex, and location.

Methods

We conducted a retrospective summary analysis of 2504 CBCT images obtained at the Department of Stomatology of Beijing Friendship Hospital, Capital Medical University from January 2021 to December 2023. Among these, 1019 were male (40.7%), and 1485 were female (59.3%). The patients’ ages ranged from 9 to 91 years (average age, 45.3 years; standard deviation, 17.94 years).

Results

Among 2504 patients, 347 (13.9%) patients exhibited BIs, including 139 (40.1%) male and 208 (59.9%) female patients. The incidence of BIs was higher in females than in males, but the difference was not statistically significant. A total of 424 BIs were identified, with 281 patients (81%) showing one BI, and 66 (19%) showing multiple BIs. The youngest patients with BIs was 11 years old, and the oldest was 88 years old (mean age, 40.71 years). Most lesions were observed in patients aged 10 ~ 29 years. The highest incidence of BIs was observed in the premolar and molar regions of the mandible. The positional relationship between jaw BIs and the teeth or lamina dura was predominantly type IV, followed by type V. Most jaw BIs were predominantly of the cortical bone type and apical-cortical bone type. Enostosis type BIs were more frequently observed on CBCT scans. Both the central sclerosis type and the enostosis type BIs exhibited both homogeneous and heterogeneous subtypes, but the homogeneous subtype was predominant.

Conclusions

BIs can occur at any age, and any location, and without sex predilection. They usually only require prompt diagnosis, highlighting the importance of careful diagnostic evaluation of radiographic findings in dental examinations. The impacts of different types of BIs on dental health and the associated treatment strategies remain unclear, highlighting the need for further research in this area.

Background

In daily clinical practice, oral physicians frequently utilize cone-beam computed tomography (CBCT) to evaluate the complexity of impacted tooth extraction, plan implant placement, and assess pre-treatment conditions in orthodontic cases. During these examinations, high-density mass-like shadows within the jawbone are commonly detected. However, non-specialists in oral and maxillofacial surgery or oral radiology may find it challenging to accurately differentiate between lesions that necessitate further intervention and those that do not require specific management. Therefore, a clear understanding of the characteristics and differential diagnosis of common high-density lesions in the jawbone is essential. This article focuses on bone island (BI), one of the frequently encountered benign high-density lesions in the jaw.

BIs, also known as enostosis, or idiopathic osteosclerosis (IO), are small pieces of mature dense bone inside the cancellous bone that reflect developmental errors occurring during the internalization of cartilage into bone [1]. Most BIs are asymptomatic and are identified on radiographs obtained for other reasons [2]. BIs in the jaws present as dense and sclerotic shadows within the jawbone or at the root apex, with clear boundaries and various shapes, such as circular, elongated, or irregular. Most previously described BIs were smaller than 2 cm [3, 4]. “Giant” BIs, defined as lesions larger than 2 cm, have also been reported [4–7]. The main body of BIs typically exhibits a homogeneous and dense shadow with uniform density. Occasionally, shadows with uneven or lower density are observed. Small blood vessels or nerves may also pass through them. Histologically, BI presents as a small fragment of dense cortical bone embedded within cancellous bone. It exhibits a mature lamellar bone structure, surrounding the Haversian system and arranged radially, with spiny trabeculae extending radially outward from the BI and fusing with the trabeculae of the surrounding cancellous bone [4, 8]. Occasionally, BIs may also contain non-lamellar, immature reticulated bone foci [8, 9]. BIs do not show a low-density transmission edge, and most BIs are closely adherent to surrounding anatomical structures (e.g., the lamina dura at the root apex, the cortical bone of the jawbone, the mandibular canal wall, maxillary sinus wall, the nasal base, etc.), or exhibit radial or filamentous edges connected to these structures.

The increasing application of CBCT in clinical practice has significantly enhanced the detection rate of jaw BIs. In comparison with traditional two-dimensional imaging techniques such as full-mouth periapical radiography and panoramic tomography, CBCT allows more precise visualization of the morphology, location, extent, and relationship of BIs with surrounding tissues. However, many clinicians remain insufficiently aware of the variations in BIs during pre-implantation and orthodontic radiographic evaluations. This study aimed to analyze the CBCT image data of jaw BIs, investigate the characteristics influencing their occurrence, and evaluate the correlations of their incidence, and distribution with factors such as age, sex, and anatomical location, thereby providing valuable references for clinical decision-making.

Materials and methods

Clinical Data

The study was approved by the ethics review board of Beijing Friendship Hospital, Capital Medical University (BFHHZS20250026). CBCT data were retrospectively collected from 2504 patients who underwent assessments at the Department of Stomatology at Beijing Friendship Hospital, Capital Medical University, between January 2021 and December 2023. CBCT images were acquired for purposes unrelated to this study, such as orthodontic evaluation and planning for wisdom tooth extraction. And CBCT images were acquired from a CBCT scanner (NewTom CT, Cefla QR Verona; Verona, Italy) with a viewing field of 18 × 16cm² or 12 × 8 cm², voxel spacing of 0.3 mm (an isotropic voxel size of 0.3 mm), exposure parameters of 110 kV, 3.0–6.9 mA (depending on subject size), and 3.6 s. Only CBCT datasets with high-quality images and fully intact upper and lower jawbones were included in the analysis.

Finally, the dataset included images from 1019 males (40.7%) and 1485 females (59.3%), with ages ranging from 9 to 91 years (mean age, 45.3 years).

Diagnostic criteria for BIs

The diagnosis of BI was established on the basis of radiological criteria and clinical symptoms. Lesions exhibiting the following characteristics were included:

1. Well-defined, dense, radiopaque masses within the maxilla and mandible [3, 10–14];

2. Without radiolucent margins [10, 14, 15];

3. Symptomless [3, 10–12];

4. Not attributable to other causes upon clinical examination [12].

Lesions that met the following characteristics were excluded:

1. Cemental hyperplasia, cementomas, odontomas or other tumors inducing osteosclerosis of the jawbones [11, 14];

2. Local osteosclerotic areas associated with a history of trauma or surgery [12, 13];

3. Large restorations, deep caries, or apical lesions of teeth leading to osteosclerosis [11–13, 16];

4. Evident remnants of deciduous or permanent teeth [11–16];

5. Solitary radiopacities in edentulous regions due to potential residual condensing osteitis [11, 12, 14, 15];

6. Radiopacities observed in patients with Gardner’s syndrome, familial adenomatosis of the colon, or other metabolic bone disorders [12, 14, 15].

Classification criteria for BIs in the jawbone

On the basis of the study by Geist et al. in 1990 [17], BIs in the jawbone were categorized into five types (Table 1; Fig. 1) according to their positional relationship with teeth and the lamina dura [16, 18].

Table 1.

Classification of the positional relationship between BIs and teeth, as well as the lamina dura

Classification	Definition
Type I (Interradicular)	Positioned around the tooth root and connected to the lamina dura of the adjacent tooth, with the periodontal ligament image clearly visible.
Type II (Isolated Interradicular)	Confined between two roots and not extending to the lamina dura of the adjacent teeth.
Type III (Isolated Apical)	Positioned between the apices of two tooth roots, clearly separated from the adjacent tooth roots and lamina dura, with the periodontal ligament image distinctly visible.
Type IV (Completely Isolated)	Completely disassociated from the tooth and the lamina dura.
Type V (Apical)	Primarily concentrated in the apical region of the root, with the periodontal ligament image clearly visible.

Fig. 1.

The positional relationship between BIs and teeth, as well as the lamina dura A: Type I (Interradicular); B: Type II (Isolated Interradicular); C: Type III (Isolated Apical); D: Type IV (Completely Isolated); E: Type V (Apical). a: parallel section, b: cross section, c: horizontal section.

Considering the positional relationship between BIs and the teeth, as well as surrounding anatomical structures as described in the study by He Shuang-shuang et al. [8], BIs were also classified into four types (Table 2; Fig. 2) based on their association with normal anatomical features such as the lamina dura in the root apex area, the cortical bone of the jaw, the maxillary sinus wall, and the mandibular canal wall.

Table 2.

Classification of the positional relationships between the BIs and anatomical structures such as the lamina dura, cortical bone, maxillary sinus wall, and mandibular canal wall

Classification	Definition
Apical type	Positioned in the apical region of the tooth root and connected to the lamina dura at the root, the lesion may involve single-rooted teeth, multi-rooted teeth, or multiple teeth. However, it exhibits no adherence to the cortical bone of the jawbone, the maxillary sinus wall, or the mandibular canal wall.
Cortical bone type	Connected to the cortical bone of the jawbone, the maxillary sinus wall, the nasal base bone wall, and the mandibular canal wall, the same BI lesions may involve one or more of these structures, but remain unattached to the lamina dura.
Apical-cortical bone type	Connected to both the lamina dura at the root and various anatomical structures including the cortical bone of the jawbone, the maxillary sinus wall, the mandibular canal wall, and the nasal base bone wall.
Isolated type	Positioned at any location within the jawbone but not connected to the lamina dura in the apical region, the cortical bone of the jawbone, the maxillary sinus wall, the mandibular canal wall, or adjacent structures such as the nasal base cortical bone.

Fig. 2.

The positional relationships between the BIs and anatomical structures such as the lamina dura, cortical bone, maxillary sinus wall, and mandibular canal wall A: Apical type; B: Cortical bone type; C: Apical-cortical bone type; D: Isolated type

On the basis of the classification criteria proposed by Koichi Yonetsu in 1997 [15], BIs were categorized into two types (Table 3) according to their relationship with the cortical and cancellous bone of the jawbone. These types are further classified as homogeneous and heterogeneous depending on the uniformity of the bone density (Fig. 3).

Table 3.

Classification of the relationship between BIs and cortical and spongy bone

Classification	Definition
Enostosis type	In a specific region of the jawbone, the cortical bone on either the labial/buccal side or the palatal/lingual side undergoes thickening.
Central sclerosis type	A dense radiolucent area is observed within the cancellous bone.

Fig. 3.

The relationship between BIs and cortical and spongy bone A: Homogeneous subtype of the enostosis type; B: Heterogeneous subtype of the enostosis type; C: Homogeneous subtype of the central sclerosis type; D: Heterogeneous subtype of the central sclerosis type

Statistical Methods

Statistical analysis was performed using SPSS 24.0 software. Count data were expressed as rates (%), and the association between the prevalence of BIs and age and sex was analyzed using the Chi-square test. A p-value <0.05 was considered as statistically significant.

Results

Prevalence of BIs

Among 2504 CBCT scans from patients, 347 exhibited BIs, corresponding to an incidence rate of 13.9%. A total of 424 BIs were identified. Specifically, 281 cases (81%) showed a single BI, while 66 cases (19%) involved multiple BIs, including 57 cases with two BIs, seven cases with three BIs, and two cases with four BIs.

Relationship between the incidence of BIs and sex

Among the 347 patients with BIs, 139 were male (40.1%) and 208 were female (59.9%). Although the incidence of BIs was higher in females than that in males, the difference was not statistically significant (P>0.05).

Relationship between the incidence of BIs and age

Among the 347 patients with BIs, the youngest was 11 years old, and the oldest was 88 years old (mean age, 40.71 years). A statistically significant difference was observed in the incidence of BIs across different age groups (χ2 = 34.030, P<0.05), indicating that the incidence of BIs varied among different age groups. In the multivariate analysis, the incidence of BIs was higher in the 10 ~ 19, 20 ~ 29, 30 ~ 39, 40 ~ 49, 50 ~ 59 age groups compared to the age group over 70, and the highest was in patients aged 10 ~ 29 years (Table 4).

Table 4.

Age distribution of patients with BI in the study population, and binary logistic regression analysis of age groups associated with the incidence of BIs

Age groups(years)	Number (n)	BIs present (n)	Incidence (%)	OR	95%CI	P
0 ~ 9	2	0	0	0.000	0.000	0.999
10 ~ 19	248	46	18.5	3.009	1.602–5.653	0.001
20 ~ 29	288	52	18.1	2.910	1.564–5.415	0.001
30 ~ 39	453	76	16.8	2.663	1.466–4.836	0.001
40 ~ 49	440	61	13.9	2.126	1.158–3.901	0.015
50 ~ 59	427	63	14.8	2.286	1.248–4.189	0.007
60 ~ 69	447	35	7.8	1.122	0.590–2.136	0.725
70~	199	14	7.0	1
total	2504	347	13.9

Common sites of BIs

BIs were more frequently observed in the mandible, with mandibular BIs constituting 87% of all cases. In both the mandible and maxilla, BIs were predominantly observed in the premolar and molar regions, followed by the anterior tooth region (Table 5).

Table 5.

Prevalence of BIs in the jaws (n, %)

Section	Anterior tooth region	Anterior tooth to premolar region	Premolar region	Premolar to molar region	Molar region	Total
Maxilla	10 (2.4%)	8 (1.9%)	17 (4.0%)	5 (1.2%)	15 (3.5%)	55 (13%)
Mandible	58 (13.7%)	38 (9.0%)	120 (28.3%)	42 (9.9%)	111 (26.2%)	369 (87%)
Total	68 (16%)	46 (10.8%)	137 (32.3%)	47 (11.1%)	126 (29.7%)	424 (100%)

The positional relationship between the BIs and teeth as well as the lamina dura was most frequently characterized as type IV, followed by type V and type I. In the maxilla, type I relationships were more common for BIs, whereas in the mandible, type IV relationships were more prevalent (Table 6).

Table 6.

Distribution of the types of mandibular and maxillary Bis: relationship with the teeth and lamina dura (n, %)

Location	Type I (Interradicular)	Type II (Isolated Interradicular)	Type III (Isolated Apical)	Type IV (Completely Isolated)	Type V (Apical)	Total
Maxilla	21 (5%)	8 (1.9%)	2 (0.5%)	8 (1.9%)	16 (3.8%)	55 (13%)
Mandible	85 (20%)	33 (7.8%)	20 (4.7%)	135 (31.8%)	96 (22.6%)	36 (87%)
Total	106 (25%)	41 (9.7%)	22 (5.2%)	143 (33.7%)	112 (26.4%)	424 (100%)

The positional relationship between BIs and structures such as the lamina dura, cortical bone, maxillary sinus wall, mandibular canal wall, was more frequently categorized as either the cortical bone type or the apical-cortical bone type. In the maxilla, the apical-cortical bone type was the most common, whereas in the mandible, the cortical bone type was predominant (Table 7).

Table 7.

Distribution of the types of BIs in the maxilla and mandible: positional relationships with the lamina dura at the root apex, cortical bone, maxillary sinus wall, mandibular Canal wall, etc. (n, %)

Location	Apical type	Cortical bone type	Apical-cortical bone type	Solitary type	Total
Maxilla	3 (0.7%)	16 (3.8%)	31 (7.3%)	5 (1.2%)	55 (13%)
Mandible	12 (2.8%)	176 (41.5%)	159 (37.5%)	22 (5.2%)	369 (87%)
Total	15 (3.5%)	192 (45.3%)	190 (44.8%)	27 (6.4%)	424 (100%)

Relationship between BIs and cortical and medullary bone

Enostosis type BIs were more frequently observed on CBCT, constituting 54.4% of cases. The central sclerosis type accounted for 45.5% of all cases. Both the enostosis and the central sclerosis types exhibited two subtypes: homogeneous and Heterogeneous. Notably, the homogeneous subtype was predominant, accounting for 83.0% of the cases, whereas the Heterogeneous subtype accounted for only 17.0% of the cases (Table 8).

Table 8.

Classification of endogenous type and central sclerosis type BIs (n, %)

Type	Homogeneous type		Heterogeneous		Total
	Maxilla	Mandible	Maxilla	Mandible
Enostosis	22	170	3	36	231 (54.4%)
Central sclerosis	25	135	5	28	193 (45.5%)
Total	47	305	8	64	424 (100%)
	352 (83.0%)		72 (17.0%)

Discussion

BI is a small piece of mature dense bone inside the cancellous bone. Most scholars believe that BIs result from developmental errors during the normal endochondral ossification process, which alters the normal bone turnover or maturation through excessive bone deposition [4, 10, 11, 16, 17]19–21– [22]. However, since BI lesions are most frequently found located in the premolar and molar regions, they may represent residual roots from deciduous molars that have been resorbed and replaced by sclerotic bone [23–26]. Histological examinations in the study by Henrikson et al. [27] clearly demonstrated sclerotic bone containing a retained root in one case. Thus, microscopic root fragments may serve as a nidus for bone proliferation in some cases [20]. Some scholars believed that excessive and improper occlusal force and traumatic movement of teeth may also lead to bone deposition within the jawbone, leading to BI formation [17, 28].

The reported incidence of BIs in the jawbone in both domestic and international studies ranges from 1.84 to 31.00% [10–15, 17–19, 29–31]. In this study, the incidence of jaw BIs was 13.9%, and it showed no statistically significant differences between males and females, a finding consistent with most previous domestically and internationally reports [10–16, 19, 20]. However, some studies have suggested that females may be more predisposed to developing jaw BIs [10]13, 14– [15, 30]. In this study, the majority of jaw BIs were solitary, which aligns with findings previous studies [11, 15, 20, 31]. When multiple BIs or osteomas, which exhibit radiographic features similar to those of BIs, are present, Gardner’s syndrome (familial multiple polyposis syndrome) should be considered. Occasionally, osteomas may be absent, but the presence of multiple BIs could still suggest Gardner’s syndrome [32].

BIs can occur in patients of any age [11]. According to the description by Petrikowski and Peters [16], the earliest age at which a BI is detected is 9.4 years (mean age, 14.0 years). In this study, the youngest patient was 11 years old. We observed that the incidence of BIs was higher in patients aged 10 ~ 29 years, consistent with findings reported previously [1, 12]. Other studies [2, 5, 11, 20] have shown that BIs are more commonly observed in the third and fourth decades of life. In this study, the incidence of BIs differed significantly among different age groups. However, some other studies [11–13, 15, 22] have reported no statistically significant differences among age groups.

Some reports have also suggested that the shape, size, and location of BIs may change with age [10, 18]. A longitudinal study with a follow-up period of up to ten years indicated that at least 40% of BIs enlarge over time, with the most pronounced changes observed in lesions detected during adolescence. Thus, BIs are more labile in younger populations and retain the potential to expand [16]. However, the results of another longitudinal study, with a mean follow-up period of 10.4 years and a mean participant age of 44.0 years, indicated that BIs in middle-aged to older adults tend to remain stable [33]. Situo Wang et al. [12] observed that IOs are labile lesions that may develop in early stages of life, and they show minimal changes once the affected individual is mature and remain relatively stable in the middle stage of life. Interestingly, BIs appear to respond to systemic hormonal influences; for instance, complete disappearance of a BI was observed in a patient with hyperparathyroidism. This lesion recurred when the causative adenoma was removed, highlighting the importance of local factors and emphasizing the lability of BIs [34]. Therefore, in this study, we excluded patients with systemic diseases such as hyperparathyroidism syndrome and Gardner syndrome.

In this study, the incidence of jaw BIs was significantly higher in the mandible than in the maxilla, consistent with the findings of previous studies [8, 10]. The highest incidence of BIs was observed in the premolar and molar regions of the mandible, as described previously [3, 5, 14, 17, 19–21, 30, 33]. The most common location was in the premolar region, consistent with the findings reported by Geist and Katz [17] and Sun et al. [35]. However, other studies [2, 5, 11, 15] have reported that the molar region of the mandible is the more frequent site for BIs. The positional relationship between jaw BIs and teeth or lamina dura was predominantly type IV, followed by type V. In contrast, studies by Situo Wang et al. [12] and Song Xue-juan et al. [18] found type V to be more common. Sisman Y et al. [11] reported that most BIs were associated with the root apices. The positional relationship between jaw BIs and anatomical structures such as cortical bone, bone cortex, maxillary sinus wall, and mandibular canal was predominantly of the cortical bone type and apical-cortical bone type.

BIs of the jawbone are usually asymptomatic; however, in rare cases, they may lead to root resorption, nerve compression, dental impaction, dental displacement, or difficulties in orthodontic movement [36]. The connection of BIs with the periapical lamina dura or their location between tooth roots can potentially lead to root displacement, resorption or challenges during tooth extraction. Cortical bone type or enostosis type may exert pressure on the cortical bone of the jawbone, the maxillary sinus wall, or mandibular canal wall, resulting in structural displacement. The apical-cortical bone type has potential effects on teeth and adjacent anatomical structures, whereas the isolated type tends to have a relatively minor impact [8]. In orthodontic treatment, it is important to evaluate the impact of apical and apical-cortical bone type, which are closely associated with teeth, on tooth movement. When placing dental implants, efforts should be made to minimize contact between the implant and the BI to prevent excessive local heat generation. However, the influence of jaw BIs on the success rate of implant surgery requires further follow-up observation. A solitary radiopaque area with no connection to a tooth is generally best left untreated. However, if a dense radiopaque area is associated with a secondary infection via an adjacent tooth, any surgical procedure should be performed with caution after the tooth is removed [5]. BIs occurring around the apices of deciduous teeth are rare but may interfere with the normal eruption of permanent teeth. In such cases, follow-up observation is recommended [8].

In this study, the vast majority of BIs were homogeneous, and only a small percentage exhibited heterogeneity. In our assessment of the relationship between jaw BIs and the cortical and medullary bone of the jawbone as depicted on CBCT, both the central sclerosis type and the enostosis type BIs exhibited both homogeneous and heterogeneous subtypes. Some scholars have argued that the enostosis type and the homogeneous subtype of central sclerosis type BIs represent normal anatomical variations rather than reactive hyperplasia, whereas the heterogeneous subtype of central sclerosis type BIs represents reactive hyperplasia [15]. However, in the present study, both homogeneous and heterogeneous subtypes were identified in enostosis type BIs. These findings may imply that the heterogeneous subtype of BIs represents a developing and maturing stage, and this subtype eventually evolves into the homogeneous subtype with increased calcium salt deposition [3].

Prompt identification of BIs and differentiation from clinically more significant bone lesions, such as primary or metastatic tumors, is essential [4, 9]. The radiopacity of BIs may mimic other pathologies of the jaws, such as condensing osteitis, root segments, hypercementosis, cemental apical dysplasia, ossifying fibromas, osteomas, osteoblastomas, cementoblastomas, impacted teeth, focal cemento-osseous dysplasia [10, 15, 37, 38], and, on rare occasions, complex odontomas [10, 37]. BIs can occur in any bone throughout the body, except for the jawbone, and are most frequently observed in the pelvis and long bones [9, 18, 19]. The other conditions identified in the differential diagnosis of BIs in long bones include calcifying enchondromas, medullary bone infracts, healing nonossifying fibromas, osteoid osteomas, osteoblastomas, sclerotic metastases, and osteosarcomas [9]. In long bones, the most critical distinction is between BIs and osteosarcomas or osteoblastomas [16]. In one previous study [39], a 1.1 cm × 1.7 cm lesion in the distal femur was initially thought to be a BI. However, six months later, the lesion expanded to 4.2 cm × 3.0 cm, and a biopsy confirmed osteosarcoma.

This study is retrospective and, as such, is subject to inherent selection bias, a limitation commonly encountered in all retrospective radiological studies. This bias can be attributed on the fact that the imaging data utilized were derived from a large cohort of patients treated at specific institutions during a defined time period [14]. In addition, the inclusion and exclusion criteria for this study were rigorously defined. Participants with jawbone defects, large restorations, deep caries, apical lesions, or systemic conditions such as Gardner’ syndrome that influence bone metabolism were excluded. This may also result in selection bias, and the incidence of BIs obtained in this study might be relatively low.

Conclusions

BIs of the jaw appear as dense sclerotic areas with a clear boundary. They can occur at any age, and any location, and do not show any sex predilection. Correct differential diagnosis of BIs from other radiopaque lesion is essential in dental practice. Typically, they are asymptomatic and do not require intervention. Nevertheless, regular follow-up examinations should be conducted to avoid misdiagnosis and to prevent potential harm to patients in the future. This study describes the prevalence of BIs in these patients and classifies BIs according to various classification criteria on CBCT scans. However, the impacts of different types of BIs on dental health and the associated treatment strategies remain unclear, highlighting the need for further research in this area.

Abbreviations

BI

Bone island

CBCT

Cone-beam computed tomography

IO

Idiopathic osteosclerosis

Authors’ contributions

XHZ has contributed to conception, design, interpret CBCT images, data reduction, analyses and drafted the manuscript; YY has contributed to interpret CBCT images, data reduction, analyses; JXM has contributed to conception, design, interpret CBCT images and data reduction; RTG has contributed to conception, design, interpretation of results and critically revise the manuscript. All authors contributed to multiple revisions and approved the final manuscript.

Funding

Not applicable.

Data availability

All data generated or analysed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

The study was approved by the ethics review board of Beijing Friendship Hospital, Capital Medical University (BFHHZS20250026). We have obtained informed consent over the phone from all patients (or their parents or guardian in the case of children under 16) before beginning of the study. All methods were performed in accordance with the Declaration if Helsinki and relevant policies in China.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.