Dental manifestations of the hypophosphatemic rickets – a case report

SUMMARY Rickets is a disorder of bone mineralization in children’s skeleton. It is most often associated with vitamin D deficiency, however, it can also occur due to a decrease in serum phosphate levels, which leads to inadequate tissue mineralization, with consequent skeletal deformity and growth disorders. Patients with hypophosphatemic rickets show teeth changes at the morphological and histological level, as well as on radiological images. The aim of this study was to perform clinical and radiological evaluation of dental manifestations of hypophosphatemic rickets in a four-year-old boy, as well as to point out the necessity of including a dentist in the treatment of this disease in order to prevent oral complications.


INTRODUCTION
Hypophosphatemic rickets, also known as vitamin D resistant rickets, or X-linked rickets, is an inherited syndrome characterized by inadequate cartilage and bone mineralization leading to skeletal deformities and growth disorders. It is caused by a mutation in the PHEX gene (endopeptidase responsible for the regulation of phosphate encoded by the X chromosome), leading to an increase in fibroblast growth factor 23 (FGF23), which is a regulator of renal phosphate reabsorption [1,2]. The pathophysiological mechanism is reflected in the reduction of phosphate reabsorption by renal tubules, which leads to hyperphosphaturia and hypophosphatemia, causing rickets [3]. The prevalence of the disease is 1:20,000 [4,5]. Standard treatment of these patients include the administration of oral phosphate supplements and active vitamin D [1,3]. Recently, attempts have been made to use anti-FGF23 antibodies that act on the primary disease by blocking FGF23 and thus regulating phosphate homeostasis [1,2]. Hypophosphatemia is the cause of dentin dysplasia due to disorders in the mineralization of the dentinal matrix when the globular dentin is clearly observed. Tubular defects are also present, which can extend to the dentin-enamel junction. In addition to disturbances in mineralization, thin enamel, dentinal clefts, especially large pulp chambers, as well as prominent pulp horns that extend to the dentin-enamel junction could be clearly observed on radiological images [4]. There are indications in the literature that patients with hypophosphatemic rickets are characterized by the appearance of multiple spontaneous periapical abscess-es [5,6,7]. Among dental characteristics, taurodontism, poorly defined lamina dura and hypoplasia of the alveolar ridges could be also present [6,8].

CASE REPORT
A four-year-old boy was referred from the Clinic of Pediatrics, Clinical Center Niš, due to oral complications related to hypophosphatemic rickets. The treatment of the rickets included treatment with phosphate supplements and active form of vitamin D, which led to the correction of clinical and laboratory findings.
General examination revealed a patient with clinical characteristics of the rickets: deformity of the lower extremities, changes in gait and short stature. No extraoral changes were observed. Intraoral examination revealed that all teeth of deciduous dentition were erupted. In the upper jaw, all anterior teeth were completely destructed by decay and residual roots were present. According to the father, there was swelling in the area of the anterior teeth previously, and a dentist provided first aid but further cooperation with the child was not established. Circular decay was observed on the upper canines, large carious lesions with open pulp chamber and necrotic pulp were observed on the upper first molars, while superficial caries in occlusal fissures was observed on the upper second molars. In the lower jaw, anterior teeth were heavily destructed, large class V caries on the canines, large carious lesions with open pulp chamber, necrotic pulp and class V cavities on the first molars, and class I cavities on the second molars were observed. According to the father, there was no swelling in the lower jaw ( Figure 1 and 2).
The analysis of the panoramic radiograph showed the presence of unerrupted permanent teeth, unerrupted first and second mandibular molars and first maxilarry molars. On the deciduous molars, large pulp chambers with prominent horns were clearly visible. The chambers of the other deciduous teeth could not be examined due to large carious destructions ( Figure 3).
The recommended treatment included conservative restoration of all four deciduous second molars, which was postponed due to lack of child cooperation. Since extractions of necrotic teeth would lead to even more intensive odontophobia, frequent controls were recommended. Parents were instructed on the need to maintain good oral hygiene.

DISCUSSION
Hypophosphatemic rickets is a skeletal disorder that is characterized by hypophosphatemia. As phosphate is essential for mineralization, this condition affects the tissues in which mineralization takes place physiologically -bones, teeth and the growth plate cartilage [1]. The presence of dental malformations in patients with hypophosphatemic rickets has been reported in numerous studies [7,9,10]. Teeth in patients with hypophosphatemic rickets show enlarged pulp chambers, a wide zone of predentin, visible globular dentin, and defects in tubular dentin that extend from the pulp to enamel. Enamel is thin, usually normal structure, but sometimes can be hypoplastic [6,7]. Histological sections can also show extensive enamel cracking and fissuring, as well as defects in dentin mineralization. Unmerged dentin calcospherites are observed and separated by large non-mineralized interglobular spaces [10].
Although odontoblast function is normal, hypophosphatemia leads to poor mineralization which causes dentin dysplasia with clearly visible globular dentin. Due to the period of formation and mineralization of dentin in deciduous teeth in the period from 4 months in utero to 11 months of age of the child, defects in deciduous dentition usually cannot be prevented [6,7]. If the treatment of the rickets starts as soon as possible after birth, it could be expected to have a positive effect on the formation and development of permanent teeth [6]. However, despite treatment, abnormalities in tooth development and dentin formation in permanent dentition could be observed [7]. Radiological findings in such patients most often show thin enamel, decreased radiological density of dentin, enlarged pulp chambers, prominent pulp horns, taurodontism and anodontia [8,10].
The dominant feature of this disease is the appearance of multiple spontaneous periapical abscesses [4,5,7,10]. These abscesses can also occur on teeth that show no signs of caries or trauma. Clinically, the patient's teeth may look normal and healthy, which complicates proving the endodontic origin of the infection and makes it difficult to identify causing teeth. This specificity can be explained by defects in dentin mineralization. Initial caries or even initial attrition can remove a thin layer of enamel, which facilitates the access of microorganisms to the pulp chamber through the exposed horn of the pulp or through poorly mineralized dentin. Thus, a seemingly non-carious or minimally carious tooth could be subject to infection   of the pulp tissue and formation of periapical abscess [4]. Light microscopic examinations showed penetration of microorganisms through enamel microcracks and their further spread along the dentin-enamel junction [5].
Data on the association of hypophosphatemic rickets with the occurrence of malocclusions were not frequently reported. In a study by Souza et al. (2010) that included 20 patients, it was reported that open bite was the most frequent anomaly that can be explained by delayed maxillary growth in relation to the growth of mandible. Although reported as a common occurrence in the literature, none of their patients showed taurodontism [6].
The therapeutic approach is mainly related to the treatment of periapical abscesses. These abscesses, especially those in deciduous teeth, spread rapidly through the jawbone, which is why extraction of such teeth is necessary [6,7]. Prevention of abscess formation should involve the application of self-etching adhesive systems and filling the tooth surfaces with light-cured flowable resin to form a barrier that would prevent the penetration of microorganisms. Deciduous teeth treated this way should be frequently checked, and, if necessary, resin barriers should be repeated until the teeth exfoliate [10]. At the same time, fluoride should be applied, and oral hygiene should be rigorously maintained. Prophylactic protection of deciduous molars with metal crowns and protection of anterior teeth with composite resins were also found in the literature [4]. However, this protection measure is often criticized because during the preparation of the teeth, the already enlarged pulp could be open, but also if multiple extractions of deciduous posterior teeth are needed it leads to the loss of the vertical dimension [7]. Preventive pulpotomy of all deciduous teeth with superficial caries is also mentioned as one of the treatment options [4,5].

CONCLUSION
Hypophosphatemic rickets, as a rare form of rickets, present a diagnostic challenge and require extensive labora-tory and clinical examinations. Early diagnosis is of great importance in order to prevent the occurrence of bone deformities, as well as dental complications and invasive dental procedures. Medicinski fakultet u Nišu, Odsek za stomatologiju, Niš, Srbija