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Micromorphologic features of dentin in vitamin D-resistant rickets: correlation with clinical grading of severity.

This study was a histological analysis of 20 primary teeth from 5 patients with 3 clinical grades of vitamin D-resistant rickets (VDRR). The results showed that the degree of globular dentin formation in the histological sections may be graded into Grades I-III in increasing order of severity. In Grade I, the amount of globular dentin was less than 50% of the total dentin thickness, and the interglobular spaces were small. By contrast, in Grade III severity, globular dentin extended throughout the entire thickness of dentin, and the interglobular spaces were large. In Grade II severity, the amount of globular dentin was more than half but did not involve the entire dentin thickness. These histologic grades of severity correlated directly with the clinical grades of the patients. In addition, the study found that lack of medical treatment in affected mothers might lead to globular dentin formation in the fetus in-utero. Conversely, adequate phosphate supplementation in a hypophosphatemic mother might prevent the formation of globular dentin in the fetus.

Adolescent

Dental phenotypes associated with novel PHEX variants in X-linked hypophosphatemia.

OBJECTIVES: X-linked hypophosphatemia (XLH) is a genetic disorder related to bone, mainly due to the mutations in PHEX gene. Previous studies have reported that XLH patients had various tooth phenotypes. It is unclear whether there are any rules about these abnormal tooth phenotypes, especially in those XLH cases with PHEX mutations. The objectives of this study were to find the most representative dental characteristics of XLH and the possible phenotype-genotype correlation. DESIGN: Two unrelated patients with XLH underwent clinical, radiographic, biochemical, and genetic evaluation. Whole-exome sequencing and whole-genome sequencing were used to identify pathogenic variants. The ultrastructure of extracted teeth was analyzed using a stereomicroscope, micro-CT, and scanning electron microscopy. In addition, a PubMed search (up to January 2026) identified 22 articles involving 366 patients for descriptive phenotype comparison. RESULTS: Two novel PHEX variants were identified: a novel complex structural variant (NC_000023.11, g.22035649-22041668delins) and a novel heterozygous splice-site variant (NM_000444.6, c.850-1 G>A). Radiographic examination showed enlarged pulp chambers and irregular pulp morphology. Ultrastructural analysis revealed dentin defects, including globular dentin, irregular interglobular dentin, disrupted dentinal tubules, and exposed collagen fibrils. Literature-based analysis indicated prevalent clinical manifestations (pulp necrosis, tooth loss, periodontitis) and radiographic findings (enlarged pulp chamber, and prominent pulp horn). CONCLUSION: In these two patients, novel PHEX variants were associated with a recurrent dentin-pulp phenotype. Integrated clinical, radiographic, ultrastructural, and literature evidence supports dentin defects as a central component of the dental phenotype in XLH and underscores the importance of early dental assessment.

Humans

The crystallinity of human deciduous teeth in hypophosphataemic vitamin D-resistant rickets.

Five teeth were obtained from three patients with hypophosphataemic vitamin D-resistant rickets (HVDRR) and five corresponding sound teeth from five healthy children. According to powder X-ray diffraction analysis, the half-peak breadths of (310) and (002) reflections of HVDRR dentine were smaller than those of normal dentine. Splitting fractions obtained from i.r. spectral analysis of HVDRR dentine powder were larger than those of normal. Microbeam X-ray diffraction analysis showed that the relative half-peak breadths of globular dentine in ground sections of HVDRR teeth were smaller than those of normal circumpulpal dentine. Transmission electron microscopy demonstrated that the hydroxyapatite crystals of globular dentine in HVDRR teeth were larger than those of normal dentine. Thus the crystallinity of deciduous tooth dentine in HVDRR was greater than that of normal dentine, mainly because of the large hydroxyapatite crystals in HVDRR globular dentine.

Child

Microscopic and crystallographic examinations of the teeth of the X-linked hypophosphatemic mouse.

Teeth from the C57BL/6J-Hyp mouse (Hyp mouse) were examined histologically, radiographically, and crystallographically. Microscopic examinations of the ground sections, the decalcified and H-E-stained sections, and the contact microradiograms of molars and incisors from the Hyp mouse showed several abnormalities--such as large pulp chamber, wide predentin, thin dentin at the pulp floor, and multiple occurrences of interglobular dentin. Powder and microbeam x-ray diffraction analyses showed that the crystallinity of hydroxyapatite in incisor globular dentin from the Hyp mouse was higher than that in incisor dentin from the normal mouse. On the other hand, the findings of transmission electron microscopy demonstrated that the sizes of hydroxyapatite crystals of globular dentin in the Hyp incisor were larger than those in normal incisor dentin. These results demonstrated that the findings in Hyp mouse teeth were in accord with those of human XLH teeth.

Animals

X-ray microanalysis of teeth from healthy patients and patients with familial hypophosphatemia.

Energy-dispersive X-ray microanalysis was used to determine calcium/phosphorous (Ca/P) ratios in undecalcified teeth, and the sulfur (S) content of dentin of decalcified teeth from normal patients and patients with familial hypophosphatemia, in an attempt to determine the effect of phosphorus deficiency. The results showed that normal enamel has a slightly elevated Ca/P ratio compared to pure apatite. Enamel from a tooth of an untreated patient with hypophosphatemia exhibited a significantly higher Ca/P ratio than the normal teeth whereas enamel from teeth of an intermittently treated patient exhibited Ca/P ratios similar to pure apatite. Surprisingly, globular dentin in the same teeth showed a Ca/P ratio similar to that of globular dentin of the untreated tooth. The decalcified dentin from teeth of three hypophosphatemic patients and eight normal patients showed a S peak which varied widely in concentration. No detectable differences could be found between normal and diseased teeth.

Adolescent

Mineral metabolism and microstructural defects in primate teeth.

There are numerous structural defects that occur in primate teeth due to variable calcification during certain growth stages. These interruptions are usually areas of hypomineralization in enamel and dentin which are referred to as Striae of Retzius and Hunter Shreger bands in the enamel or Incremental Lines of von Ebner and Contour Lines of Owen in the case of the dentin. The frequency of occurrence of these variations in mineralization can be related to such factors as growth tempo, dietary quality, state of health, and past disease episodes. Another structure that appears in the dentin is a region that fails to calcify and is referred to as Inter-globular Dentin. Our studies have shown that the microstructural quality of different species' dentition varies widely. Samples obtained from certain fre-ranging cercopithcoids show that these species have the least hypomineralizations while man has the most. Other primate species range between these two extremems with the pongids nearer to man in these characteristics, as previously noted by Sognnaes. Additionally, out initial study shows a great deal of diversity between prehistoric human populations in the microstructural quality of their teeth. We offer the tentative explanation that this variation is due to differences in the calcitying properties of the diet and hence a difference in the general state of their health.

Adolescent

Long-term (8 days) effects of exposure to low concentrations of fluoride on enamel formation in hamster tooth-germs in organ culture in vitro.

Second maxillary molars of 3-4-day-old hamsters were cultured for 7-8 days in the continuous presence of fluoride (F-) or chloride in concentrations between 2.63 microM and 1.31 mM. For biochemical study, explants were labelled during the last 24 h of culture with a triple label of [3H]-proline, 45Ca and 32PO4. The 3H-labelled presumptive amelogenins were separated from the 3H-labelled dentine collagens by a three-step extraction procedure. Histologically, chronic exposure to F- had no obvious effects below 26.3 microM; at 26.3 microM of F-, a non-mineralizing enamel matrix was observed besides that of a normal mineralizing enamel. From 52 microM of F- onwards, only a non-mineralizing enamel matrix was found in decreasing amounts extracellularly as F- concentrations increased. Except for the presence of globular dentine, dentinogenesis was not obviously affected by F-. Biochemically, total synthesis of presumptive amelogenins was hardly disturbed, but their solubility was changed by chronic F- treatment; more amelogenins became formic-acid soluble at the expense of water-soluble amelogenins. Chronic exposure to F- decreased the water-soluble amelogenin fraction according to a logarithmic function of the medium F- concentration. By extrapolation, it was calculated that concentrations higher than 1-2 microM of F- affect amelogenesis in vitro. Synthesis of dentine collagen was not affected by chronic exposure to F- in vitro. Chronic exposure to F- decreased uptake of 45Ca and to a less extent trichloroacetic acid-soluble 32PO4. Chronic F- exposure may inhibit energy production in the enamel organ resulting in an impairment of enamel matrix secretion as well as that of a trans-epithelial transport mechanism for calcium.

Amelogenesis

[Dentofacial manifestations in children with vitamin D-dependent Rickets type II].

Calcification of the teeth, size of the teeth and dental arches, facial growth and calcification of the carpal bones were studied in three children with clinically different severities of vitamin D-dependent rickets (DDR), type II, with alopecia, which is 1,25-dihydroxyvitamin D-receptor-defect rickets and is particularly resistant to treatment with calciferol analogues. They were treated in a pediatric clinic with large doses of 1 alpha-hydroxyvitamin D3(1 alpha-(OH)D3) and 2 g/day of calcium lactate. The results were as follows: 1. Hypoplasia of enamel of the deciduous teeth was not found. 2. In the deciduous teeth, large pulp chambers and thin dentin were seen in radiographs before treatment. In patients 1 and 2, these abnormalities were reversed by treatment. In patient 3, who had the severest manifestations, large pulp chambers and thin dentin decreased but still remained. 3. Growth of permanent teeth was retarded before treatment and during resistance to treatment. After effective medication, it caught up and was corrected. 4. Problems concerning maxillary and mandibular growth were not found. However Nasions of three patients were more front and lower and Orbitals were lower than standard. 5. In patients 1 and 2, the calcification of carpal bones was accelerated and in patient 3 retarded. 6. Mesiodistal dimensions of erupted deciduous and permanent teeth were within the standard range, except for patient 3, who had smaller lower deciduous teeth. 7. A ground section of the extracted upper right first deciduous molar from patient 3 showed abundant inter-globular dentin and lack of pre-dentinal layer. From the above findings, it was felt that in all probability dentinogenesis was disturbed by the DDR type II. Abnormally large pulp chambers and thin dentin could be corrected by effective medication. In patients with vitamin D-dependent rickets type II, oral hygiene for caries prevention is the most important procedure, because the pulp will be infected immediately after initiation of dental caries. After effective medication, permanent teeth and jaw bones will probably grow normally.

Carpal Bones

Odontogenic tumors in Fischer rats.

The formation of odontogenic tumors in rats is rare unless they are treated with known carcinogens. In this study, male Fischer rats were continuously fed aflatoxins M1, B1, or control diets, then killed at 1, 6, 10, 16, 17, 19 and 21 months. Of the 186 rats fed aflatoxin M1 at 3 concentrations, 12 developed odontogenic tumors; 7 of 63 rats fed an agar-based diet also developed odontogenic tumors in 17-21 months. The purpose of this study is to describe these tumors. All the tumors were located in the upper jaw associated with the incisor teeth. The tumors developed in the periodontal ligament area and were composed mainly of highly cellular fibrous connective tissue. The fibroblastic nuclei were clustered in poorly defined swirls in areas and were evenly scattered in a myxomatous stroma in other areas. Within this tissue were ovoid sometimes coalescing, calcified bodies resembling cementum. Occasional inclusions of solid epithelial cell nests were present. Scattered nests were composed of ovoid epithelial ghost cells. Acellular cementum-like material surrounded many of these nests. An inductive phenomenon was present around occasional epithelial nests. Rare structures composed of globular dentin with irregular tubules were also observed. These tumors caused distortion of the facial areas and disruption of incisor tooth development. No metastatic lesions were noted but other neoplastic lesions occurred in these animals.

Aflatoxin B1

Regional odontodysplasia: new histopathological data.

Light microscopy, microradiography, SEM and TEM of 4 tooth follicles in a 12-year-old caucasian girl presenting regional odontodysplasia showed widespread globular dentin, calcifications located in the enlarged pulp chambers, hypoplastic and hypomineralized enamel. Hypomineralized strands were sandwiched between two normal enamel layers, which indicates that amelogenesis, interrupted for a while, has once more become established. The enamel surface was covered with calcoglobules. Numerous rounded calcifications were scattered within the dental follicles. Some of these occurred in microfibrils (possibly oxytalan fibers), distinct from collagen fibers. Calcification of the sheath surrounding epithelial rests was a conspicuous feature. The fibroblasts in contact with calcifications developed numerous cytoplasmic extensions, which suggests that they may have assumed a phagocytosis behaviour.

Child

Dental involvement in congenital chloride diarrhea.

Dental involvement in a case of congenital chloride diarrhea (CCD) was studied using light microscopy of decalcified and undecalcified sections, microradiography and TEM. Mixed enamel lesions were found, involving gross hypoplasia at the cuspal level and hypocalcification occurring all over enamel. The hypocalcification resulted in the immature aspect of the prismatic enamel, porosities, amorphous areas, prominent incremental lines and round-ended crystallites. A marked hypocalcification suggests a temporary break of amelogenesis likely related to acute episodes of the disease. Globular calcifications were associated with enamel formation. Dentinal hypocalcification was conspicuous and diffuse all over dentine. A globular mineralization pattern was revealed by the tretracycline (TC) stain which was well preserved in decalcified sections, thus indicating that TC uptake is related to the organic matrix. It is unlikely that TC alone is responsible for the hypocalcified areas which extended widely beyond the TC-stained bands. It is suggested that TC uptake only adds to dental defects induced by the metabolic troubles of CCD.

Alkalosis

Scanning electron microscopic study of odontoblasts and circumpulpal dentin in a human tooth.

Two combined scanning electron microscopic methods including modified fixative procedures were used for studying the morphologic aspects of the odontoblasts and the corresponding dentinal wall at different endodontic levels. The odontoblasts were tightly packed in the pulp horn, where they assumed pear-shaped profiles and, from crown to apex, successively looked spindle shaped, club shaped, and globular. Their number decreased in the pulp radicular portion, where the interglobular spaces were enlarged. The filling fibrillar material varied from crown to apex. A globular circumpulpal dentin was observed at all levels of the root canal. The tubule openings varied in number and size.

Adult

Scanning electron microscopy of incinerated teeth.

The aim of the present scanning electron microscopy study was to document the nature of morphologic changes occurring in human enamel and dentin subjected in vitro to temperatures in the range of 200-1,000 degrees C for variable times. The results of the investigation confirm that human enamel and dentin remain microscopically identifiable after incineration at 1000 degrees C. Furthermore, these tissues remain identifiable after incineration at 1,000 degrees C for periods greater than 3 h. No consistent or reliable differences in morphology could be detected in enamel or mineralized dentin incinerated in the temperature range 200-600 degrees C. Temperature-dependent changes involving the predentin zone were observed. Following incineration at 800 degrees C for over 3 h and at 1,000 degrees C for 3 h, a metamorphosis of enamel and dentin into a globular form was observed.

Adult

Morphological study of calcospherites in rat and rabbit incisor dentin.

Calcospherites from incisors of rats and rabbits were studied, by means of secondary and backscattered electron images, using scanning electron microscopy. Part of each incisor specimen was made anorganic to allow observation of the surface of the mineralization front by scanning electron microscopy; the other part was ground on one side for observation by scanning electron microscopy with a backscattered electron image detector. In both species the labial mineralization front was wavy and the image showed fused calcospherites, whereas the lingual mineralization front appeared to consist of a combination of linear and globular forms. In rat labial dentin the calcospherites were large and globular form, but they did not develop in the lingual dentin and were small and oval. The shape and size of rabbit incisor calcospherites varied from the pulp horn to the root apex. There were great differences between rats and rabbits with respect to the size and shape of the calcospherites at the mineralization front. This may be due to species differences and possibly the differing rates of dentinogenesis in rats and rabbits.

Animals

Treatment of dentin with stannous fluoride--SEM and electron microprobe study.

The effect of SnF2-treatment of dentin surfaces was investigated by means of scanning electron microscopy (SEM) and electron microprobe analysis. Human dentin was treated with aqueous SnF2 solutions of concentrations varying from 1 to 10%. The treatment periods lasted for 1, 5, 10, or 60 min. Both tin and fluoride were identified on the surfaces. The concentration varied depending on the extensiveness of the treatment. Immersion in 1 M KOH for 15 h removed both tin and fluoride from the surfaces. This reaction was not observed after immersion in H2O for the same time period. Examination of the SnF2-treated dentin surfaces showed a dense layer of globular particles and in addition some larger particles. The dentinal tubules were totally covered even after the treatment with the lowest concentration of SnF2. Deposition of tin- and fluoride-containing globules on dentin surfaces may be of clinical interest. This layer may have importance both for the caries resistance of dentin and for hypersensitivity reactions.

Dental Caries

Oral manifestations of familial hypophosphatemic rickets after phosphate supplement therapy: a review of the literature and report of case.

The patient was a seven-year-old boy with familial vitamin D-resistant hypophosphatemic rickets. His mother, and her mother, were also affected. Before phosphate treatment was introduced in the patient, an impaired incorporation of calcium, and its exchange with sodium, was thought to be the principal etiological factor in the formation of globules. Supplementation therapy then resulted in a less elevated Ca/P ratio in the root area of the affected teeth, as well as a cure for the boy's bone structure. What the therapy did not cure was the globular appearance of the dentin and the hypomineralized stripe of pulpal horn extending to the cusp tips, an apparent permanent outcome of the disease.

Abscess

Morphological aspects of the resin-dentin interdiffusion zone with different dentin adhesive systems.

Cross-sections of resin-dentin interfaces were etched with an argon-ion beam to make their substructure detectable by scanning electron microscopy. The dentin adhesive systems were categorized morphologically into three groups, and an attempt was made to clarify their adhesive mechanism. The first group of products removed the smear layer. The argon-ion bombardment clearly disclosed a hybrid or resin-impregnated dentin layer. It is hypothesized that conditioning with acidic or chelating agents demineralized the dentin surface-layer to a certain depth, leaving behind a collagen-rich mesh-work. Hydrophilic monomers are then believed to alter this collagen-fiber arrangement in a way that facilitates penetration of the adhesive resin, resulting in a mechanical, intermingled link between collagen and the adhesive resin. The second group preserved the smear layer. In this case, the dentinal tubules were obliterated with globular particles at their orifices and remained patent underneath these smear plugs. This type of adhesive system aims at the incorporation of the smear layer into the hydrophilic monomers, which have an affinity for the organic and/or inorganic components of the underlying dentin. Finally, a third, small group only partly dissolved the smear layer, creating a thin resin-impregnated dentin layer and a resin-impregnated smear plug. This study clearly showed that the application of recent adhesive systems induced structural changes in the dentin surface morphology, creating a retentive interface, called the inter-diffusion zone, between the deep, untouched dentin layers and the composite filling material. This resin-dentin interdiffusion zone offers bonding sites for copolymerization with the resin composite and, concurrently, might have protective potential for the pulp tissues.

Acid Etching, Dental

On the configuration of incremental lines in human dentine as revealed by tetracycline labelling.

The pattern of tetracycline labelling in dentine was investigated in ground sections of human teeth under visible and ultraviolet light. The tetracycline lines presented different appearances near the enamel-junction region, near the dentine-cementum junction, in the mantle dentine, and in the circumpulpal dentine, depending on whether the mineralization front was linear, globular or linear-globular.

Cementogenesis