Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature

Xinyang Jin; Yuedan Xu; Wei Liu; Zhiwei Shi; Yi Sun; Xinni Pan; Ling Zhang; Baiping Fu

doi:10.1038/s41405-023-00129-9

Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature

Jin, Xinyang; Xu, Yuedan; Liu, Wei; Shi, Zhiwei; Sun, Yi; Pan, Xinni; Zhang, Ling; Fu, Baiping 2023-01-30 00:00:00 www.nature.com/bdjopen ARTICLE OPEN Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature 1 2 2 2 2 2 2 2 Xinyang Jin , Yuedan Xu , Wei Liu , Zhiwei Shi , Yi Sun , Xinni Pan , Ling Zhang and Baiping Fu © The Author(s) 2023 BACKGROUND: The treatment and management of patients suffering from hypophosphatemic rickets (HR) remain a major challenge for dental practitioners and affected patients. OBJECTIVES: To report a case of HR presenting with speciﬁc dental ﬁndings and to review the dental manifestations and treatment of HR patients. METHODS: Case: A 32-year-old male presented with multiple dental abscesses and short stature. A thorough history was taken followed by clinical oral examination, and relevant radiological investigation was done. Literature research: In 2020, electronic literature searches were carried out in PubMed and complemented by a careful assessment of the reference lists of the identiﬁed relevant papers. Articles and reports fulﬁlled the inclusion criteria: indexed reviews, case series and case reports in English and restricted to human studies were considered. RESULTS: The intraoral examination revealed multiple dental abscesses and general periodontal disease; the radiographic examination showed poorly deﬁned lamina dura, large pulp chambers and periapical lesions. Based on the contents of the 43 articles identiﬁed in the search, the current knowledge of dental manifestations, treatment and management of HR was summarized. CONCLUSIONS: As HR is a multisystem disease, multidisciplinary care is needed. By summarizing current evidences, we proposed an evidence-based dental management and provided recommendations on diagnosis and treatment of the disease.It is of profound clinical signiﬁcance to acquire knowledge of the dental manifestations and provide optimal treatment options for patients. BDJ Open (2023) 9:2 ; https://doi.org/10.1038/s41405-023-00129-9 INTRODUCTION PHEX, mainly expressed in osteocytes and odontoblasts, is located Hypophosphatemic rickets (HR) is a group of hereditary metabolic on chromosome Xp22.1 and encodes for an endopeptidase [10]. bone diseases caused by renal phosphate wasting, which has no Inactivating PHEX mutations contribute to the increasing secretion response of high doses of vitamin D [1]. HR is characterized of FGF23 [11]. As a key circulating factor that directs sodium- by short stature, delayed walking, bow legs, bone/joint pain, dependent phosphate transporters in the kidney and intestine, spontaneous dental abscess, hypophosphatemia, and inappropri- the high level FGF23 results in impaired proximal renal phosphate ately normal serum 1,25(OH) D level [2]. Genetic defects in factors reabsorption, causing hypophosphatemia and systemic regulation necessary for phosphate handling is the main cause of phosphate of mineralization [12]. Meanwhile, the PHEX mutations contribute wasting [3]. HR can be mainly divided into three types, including to the local accumulation of mineralization inhibitors such as OPN X-linked hypophosphatemic rickets (XLHR) due to a loss function (osteopontin) and ASARM (the acidic serine- and aspartate-rich of phosphate regulating gene with homologies to endopeptidases motif) peptides at the level of the extracellular matrix [12]. on the X chromosome (PHEX) [4], autosomal dominant hypopho- Likewise, the certain genetic mutation emphasizes the importance sphatemic rickets (ADHR) caused by mutation in the ﬁbroblast of FGF23 and DMP1 in the pathogenesis of ADHR and ARHR, growth factor 23 (FGF23) gene [5] and autosomal recessive respectively [5, 6]. As the same result of phosphate wasting, it is hypophosphatemic rickets (ARHR) as a result of mutation in dentin found that different types of HR cause similar, though not matrix protein 1 (DMP1) gene, ecto-nucleotide pyrophos- phatase/ identical, clinical and radiographical parameters, which mostly phosphodiesterase 1 (ENNP1) gene, or family with sequence depend on the duration of hypophosphatemia [1]. similarity 20, member C (FAM20C) [6–8]. Early diagnosis of HR is of great signiﬁcance, since early XLHR, also named as vitamin D resistant rickets, familial treatment promotes growth, reduces bone pain and improves hypophosphatemic rickets, or phosphate diabetes, is the most dental health [13, 14]. The diagnosis of HR is on the basis of common form of HR, with an incidence of around 1:20000 [9]. combination of clinical, radiological and biochemical ﬁndings. 1 2 Department of Stomatology, The Fourth Afﬁliated Hospital, Zhejiang University School of Medicine, Yiwu, China. Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China. email: fbp@zju.edu.cn Received: 31 October 2022 Revised: 29 December 2022 Accepted: 2 January 2023 1234567890();,: X. Jin et al. Fig. 1 Intraoral views and panoramic radiograph of a 32-year-old male patient with HR. Intraoral views (a–e) showed multiple ﬁstulas and abscesses, malocclusion, and dental attrition in the left lower incisors; Panoramic radiograph (f) revealed enlarged pulp chambers, the radiolucencies at periapical regions of teeth # 12, 13, 17, 22, 23, 32, 36, 37, 41, 42, 43 and 48, and the presence of endodontically treated teeth # 12, 13, 23 and 32. Clinically, patients of HR feature leg bowing, delayed walking, provide timely treatment options, which does help to improve the waddling gait, bone/joint pain, short stature and dental abscesses quality of HR patients’ life [26]. This article aimed at reporting a [2]. Especially, any form of leg bowing and widening of the case of male with HR, reviewing the dental manifestations and metaphysis acquire a further radiological and biomedical exam- treatment of HR patients and providing suggestions of dental ination [15]. Radiographic manifestations show the long bone management. deformities and abnormal growth plates with widened and frayed metaphyses [15]. Biomedical criteria for the diagnosis of HR includes serum phosphate below the normal threshold for age, CASE REPORT elevated alkaline phosphatase, normal or upper normal parathyr- A 32-year-old male was referred to the Department of Prosthodon- oid hormone levels, normal serum calcium, and low urinary tics with the complaint of “several abscesses that appeared in the calcium excretion [16]. In addition, a family history of the disease is mouth”. The patient was diagnosed with HR at the age of 2, but his beneﬁt for diagnosis due to an X-linked dominant inheritance parents didn’t have metabolic disorder. Since been diagnosed, he pattern of PHEX mutation. Genetic analysis, which identiﬁes was treated with oral phosphate supplementation, calcitriol and mutations in the PHEX gene in about 70% of patients with HR, is vitamin D2. In addition, he was undergoing pharmaceutical therapy the ﬁnal conﬁrmation [15]. If genetic analysis is not available, with burosumab at a dose of 60 mg/month by hypodermic injection elevated plasma levels of intact FGF23 supports the diagnosis [17]. at the age of 31. Treatment initiation is recommended as soon as diagnosis is On physical examination, the patient showed short stature, bow established [17]. Conventional treatment with oral phosphate legs, achilles tendinitis and mild hearing loss. The intraoral supplements and active vitamin D (calcitriol or alfacalcidol), has examination revealed multiple ﬁstulas and abscesses at the been proposed for decades [3, 18, 19]. This kind of therapy has periapical regions of maxillary right lateral incisor, mandibular left been shown to result in the positive outcomes of decrease in bone lateral incisor and ﬁrst molar, and mandibular right central incisor pain, normalization of alkaline phosphatase level, increase in (Fig. 1a–e). The pulpal vitality test was negative at maxillary right growth velocity, straightening of legs and improving dental lateral incisor, maxillary right canine and second molar, mandibular mineralization [3, 13, 20, 21]. However, due to the limitations, such left canine, mandibular left lateral incisor and ﬁrst molar, and as increasing risk of nephrocalcinosis, urolithiasis or hyperpar- mandibular right central incisor and third molar. Periodontal athyroidism, the dose of phosphate supplements and vitamin D examination revealed the absence of many teeth, and general analogues should be strictly controlled according to individual periodontal disease resulting in some teeth increased probing situation [22, 23]. Recently, a novel therapy with burosumab, a pocket depth of 10 mm or more. Radiographic examination in Fig. 1f kind of humanized monoclonal anti-FGF23 antibody, has been showed poorly deﬁned lamina dura and enlarged pulp chambers approved for the treatment of XLHR patients over 1 year of age in and radicular canals. Radiolucencies were detected at periapical Europe and US, with the function of increasing renal phosphate regions of maxillary right lateral incisor, maxillary right canine and reabsorption and normalizing serum phosphate [15, 24]. Never- second molar, mandibular left lateral incisor and canine, mandibular theless, all of those therapies focus on regulation of systemic left lateral incisor, mandibular left second and third molar, serum phosphate, the defects in mineral quality and quantity mandibular right central and lateral incisor, and mandibular right during formation of mineralized tissues such as tooth and bone canine and third molar. Several teeth (i.e., maxillary right lateral due to the local dysfunction of PHEX intend to be treated [11]. incisor and canine, maxillary left canine, and mandibular left lateral Given that, the disease follow-up and treatment management are incisor) had received endodontic treatment before. essential. For some patients, dental manifestations might be the ﬁrst symptom diagnosed [25]. Furthermore, early prophylaxis and LITERATURE SEARCH treatment can improve dental status [14]. Hence, broadening A literature search was carried out to identify all cases of HR knowledge of various dental manifestations of HR is required to associated dental manifestations. The PubMed database was BDJ Open (2023) 9:2 X. Jin et al. Table 1. Number of reported cases of hypophosphatemic rickets with dental manifestations. Author Year No. of cases Author Year No. of cases Gigliotti et al. [54] 1971 3 Baroncelli et al. [35] 2006 9 Sauk et al. [27] 1973 1 Chaussain-Miller et al. [14] 2007 7 Cohen et al. [28] 1976 1 Douyere et al. [36] 2009 1 Ainley et al. [29] 1978 1 Souza et al. [37] 2010 14 Nikiforuk et al. [61] 1979 26 Al-Jundi et al. [50] 2010 21 Rakocz et al. [30] 1982 1 Sh AJ et al. [51] 2010 21 Lyles et al. [58] 1985 1 Al-Jundi et al. [46] 2011 1 Bender et al. [53] 1985 50 Ye et al. [47] 2011 10 Abe et al. [59] 1988 3 Beltes et al. [38] 2012 1 Schwartz et al. [49] 1988 18 Rabbani et al. [39] 2012 19 Daley et al. [60] 1990 3 Andersen et al. [45] 2012 52 Hintze et al. [52] 1990 1 Soares et al. [44] 2013 3 Shields et al. [65] 1990 17 Rathore et al. [56] 2013 1 Chadwick et al. [31] 1992 1 Friberg et al. [64] 2013 3 Hillmann et al. [57] 1996 2 Souza et al. [25] 2013 1 Goodman et al. [32] 1998 17 McKee et al. [12] 2013 1 Resnick et al. [63] 1998 1 Cremonesi et al. [40] 2014 10 Murayama et al. [43] 2000 1 Yuan et al. [62] 2015 4 Alexander et al. [55] 2001 1 Ayesha et al. [41] 2016 1 Chaussain-Miller et al. [21] 2003 48 Biosse et al. [48] 2016 34 Pereira et al. [33] 2004 3 Paredes et al. [42] 2017 1 Batra et al. [34] 2006 1 Total cases reported 416 searched until 10 March 2020 with the following MESH term: characteristics of HR [25, 27, 32, 41, 44, 46–48, 53, 54]. “Rickets, Hypophosphatemic” and a keyword: “dental”.Itwas Other common manifestations are thinner enamel and dentin supplemented by manual searches in the reference lists of [21, 30, 40, 53], primary tooth resorption [44, 56] and short root relevant articles. The search retrieved 198 results. Articles and [43, 57]. reports including indexed reviews, case series and case reports Histopathologically, hypomineralized dentin, featured by a published in English and in peer-reviewed journals were widened predentin with fewer well-deﬁned dentinal tubules and considered, and restricted to human studies. After screening numerous unmerged calcospherites creating interglobular spaces, is the title and abstract, 43 relevant full-length articles were commonly seen in teeth of HR patients, while the mantle dentin is included. This search identiﬁed about 416 reported cases unaffected [12, 14, 21, 30–32, 37, 40, 52, 53, 55–60]. The organization [12, 14, 21, 25, 27–65], as presented in Table 1. and polarization of odontoblasts are also impaired [66]. Enamel alternation, such as numerous crater-shaped depressions and deep microcleavages penetrating into the enamel thickness, can be seen DENTAL MANIFESTATION in some patients [21, 32, 35, 37, 39, 49, 58, 61, 62]. Due to the dentin Clinically, recurrent spontaneous dental abscesses both in primary and enamel alternation, bacteria can invade easily from the oral and permanent dentition without carries, periodontal problems, cavity to the dental pulp, causing pulp necrosis in caries-free tooth traumatic injuries or restorations are common ﬁndings in HR [39]. Cementum is thinner, with roughly granular with hypominer- patients [12, 14, 21, 25, 27–44]. Meanwhile, with the increasing alized interglobular patterns [48, 67]. age, the number of endodontically affected teeth signiﬁcantly rises, and the incisors and canines usually get affected prior to molars and premolars [45]. HR patients are more prone to suffer DENTAL TREATMENT periodontal bone loss than the general population, while the Prophylaxis percentage of BOP seems to be similar without commensurate Preventing bacteria invading dentin and pulp is important to increase [33, 39, 41, 46–48]. Another main dental ﬁnding is the reduce dental abscesses [17]. Stainless steel crown was used to smaller dental arches which always accompany with crowded cover the crown of primary molar in the past [30, 55]. However, dentition and class III occlusion [29, 46, 49, 50]. Other infrequent the limitations of large pulp chamber, high pulp horn, thin enamel dental ﬁndings are ectopic permanent canines [34], delayed and hypomineralized dentin should be taken into strict considera- eruption of both primary and permanent teeth [39], delayed tion. Sealing occlusal surfaces of primary and permanent teeth dental development [41, 51] and dental hypersensitivity [52]. with composite resin is suggested, the properties of which have Radiologically, both primary and permanent teeth exhibit greatly improved over the last decade [26, 68]. It is worth noting enlarged pulp chambers with high pulp horns which sometimes that self-etch adhesive system is recommended to minimize risk of extend up to or beyond the dentino-enamel junction pulp irritation, and the sealing must be repeated every year due to [12, 21, 27, 29, 30, 32–34, 37, 39–45, 49, 52–56]. Zones of gradual wear of the resin [3]. The early monitored use of topical hypomineralized early forming coronal dentin appear as a “halo” applications of ﬂuoride is critical for preventing subsequent at the dentino-enamel junction around the circumpulpal dentin serious dental infections [33, 36–39, 42]. Tooth attrition is easier to [52, 55]. Hypoplastic alveolar ridge, reduced radiopacity of lamina be seen in HR patients for the enamel alternation, so a nightguard dura and varying degree of alveolar bone loss are also radiological acrylic splint is also suggested [53, 55]. BDJ Open (2023) 9:2 X. Jin et al. Endodontic treatment enlarged pulp chambers, periapical bone loss and pulp necrosis For the endodontically affected teeth, root canal treatment is [17]. (5) In adults, it is suggested to perform conventional the conventional choice, while extraction is necessary for those supportive periodontal therapy, including periodontal risk assess- of abscesses spread quickly in jaw bone especially in primary ment as well as supragingival and subgingival debridement twice teeth [3]. The procedures of endodontic treatment should try to a year if necessary [17]. (6) If orthodontic and implant treatment be sterile. Using sodium hypochlorite to irrigate canals and are required, it must be based on the premise that conventional Ca(OH) as intracanal medicament for a 10-day interval is therapy is correctly treated [26, 63, 64]. recommended, and the determination of working length is preferred to combine electronic apex locators and radiograph [38]. Avoiding any voids and achieving the best possible density DISCUSSION of the root canal ﬁlling are the goal of the obturation of the root HR is genetic disorders, whose main symptoms are hypominer- canal system [26]. Meanwhile, the ﬁlling of root canal might be alized skeleton and dentition [12]. Dental abscesses without caries suggested using thermoplasticized obturation techniques with a are observed most frequently in HR, even in some cases as the ﬁrst virtually insoluble sealer [26]. Apical curettage procedure and symptom diagnosed [25]. In the present report (Fig. 1), the apical barriers with mineral trioxide aggregate might be symptoms were enlarged pulp chambers and multiple dental performed in sever abscessesand open apical foramens, abscesses. The cause of dental abscesses is the enamel alternation respectively [28, 33]. and hypomineralized dentin [39]. However, the relationship between HR and hypomineralized dentin remains unclear. In the Prosthodontic treatment past, hypophosphatemia was thought to be responsible for For some mild or moderate damages, adhesive procedures can be dysplastic and poorly mineralized circumpulpal dentin with wide used, but in sever situation, such as dominant enamel fracturing areas of interglobular dentin, which limited growth and fusion of and rapid dental wear, full coverage restoration should be chosen calcospherites [69]. Recent researches have shown that the [68]. Regarding to the coronal restoration of endodontic treatment mineralization induced by human cells is disturbed independently teeth, occlusal coverage with ﬁtted stainless steel crowns is of hypophosphatemia and supported a local role for PHEX, DMP1 suggested to protect teeth from recurrent infections, however, or FAM20C in matrix mineralization [11, 70, 71]. This ﬁnding might posts cannot be supported due to the thin dentin [40, 55]. As for illustrate that conventional therapy improve dental complications the ceramic crown, it is not recommended for teeth with but not prevent [35]. Due to different mechanisms of three forms prominent pulp horns, since the preparation costs a greater loss of HR, the article mainly focused on XLHR. Several studies have of dentin than metal crown [26]. Therefore, all-ceramic occlusal conﬁrmed that PHEX regulates the mineralization of the veneer might be another choice not only as a minimal invasive extracellular matrix at the local level in mineralized bone and approach but for aesthetic reason [26]. dentin and maintains mineralized matrix homeostasis by cleaving of acidic, non-collagenous SIBLING proteins and peptides of the Periodontal treatment extracellular matrix such as OPN, MEPE (matrix extracellular Conventional supportive periodontal therapy is of great beneﬁt phosphoglycoprotein) and ARARM [66, 72, 73]. Furthermore, it is for HR patients [3]. Hence, twice-yearly visits to perform suggested that OPN and MEPE inhibit tooth mineralization conventional supportive periodontal therapy aimed to decrease through different ways, with OPN acting at the mineralized gingival inﬂammation and suppress periodontal pockets for adults calcospherites and MEPE at the region of the unmineralized is suggested [17]. interglobular dentin [66]. From the literature review (Table 1), we can ﬁnd that the Orthodontic treatment majority of reported patients are females, which seems to indicate Although it is conﬁrmed that the periodontium of HR patients is a higher HR prevalence in female. However, male patients are less prone to orthodontic treatment [67], orthodontic treatment is usually shown severer dental complications, such as taurodontism not contraindicated especially for those treated with conventional [69]. Since most cases are determined by PHEX, an X-linked systemic treatment, and could trigger extensive remodeling of the dominant mutant gene, it might be a gene dose effect [32]. The alveolar bone [68]. severity of complications might depend on three factors, including family history, medical history and age. Patients born to affected Implant treatment mother are inclined to bear poorer dental status for primary Implants are acceptable for HR patients and several successful dentition than those born to healthy mother, due to the lower cases have been reported [63, 64]. However, the successful rate is phosphate and vitamin D obtained from the affected mother declined in those who are not under conventional treatment, during fetal odontogenesis [21]. Nevertheless, a family history hence, implant surgery is recommended to be performed after 3-6 contributes to an earlier diagnosis of HR, which might take an months of conventional treatment, which should be continued for earlier treatment for patients, resulting a better outcome for 6 months following implant surgery [17]. It might be better permanent dentition [15]. Although conventional treatment is not to prolong the healing time up to 6 months to obtain a good able to prevent oral complications, its beneﬁcial effects on dental stability [64]. and periodontal tissues cannot be underestimated [35]. It has already been conﬁrmed that conventional treatment for HR patients improves mineralization of dentin and decreases the DENTAL MANAGEMENT incidence of endodontic infection in children [14, 21]. Meanwhile, In summary, the lifetime dental management for a particular the beneﬁt of continuing treatment for adults has been proved in patient is as followed. (1) Once the diagnosis is established, the permanent teeth and periodontal health recent years [48]. conventional treatment should be initiated and last a lifetime if However, the dose of medicine should depend on the age and possible [17]. (2) The dental examination should be performed stage of development, for excessive phosphate might result in twice a year regularly for adults and children, including dental hyperparathyroidism [17]. The number of endodontically affected orthopantomogram, of which the ﬁrst time is suggested at age 5 teeth raises signiﬁcantly with age, due to the exposure of [17, 68]. (3) Typical ﬂuoride application and pit and ﬁssure sealing defective dentin [45]. Thus, only incisors or canines are affected both in primary and permanent teeth should be carried out as in younger patients and affected posterior teeth are more soon as acquired [40, 42]. (4) We recommend a thorough dental commonly seen in older patients [45]. Similar situation is present examination clinically and radiologically searching for all of the in the case report (Fig. 1). BDJ Open (2023) 9:2 X. Jin et al. In order to decrease the risk of dental abscess, preventive CONCLUSION approaches, such as topical ﬂuoride application, pit and ﬁssure HR is associated with marked dental manifestations and patients sealing, stainless steel crown and nightguard acrylic splint are with them exhibit a tendency of poorer quality of life. Early proposed for decades [30, 33, 55]. As the using of conventional diagnosis, treatment and management are the keys to successful steel crown requires tooth preparation which might cause the outcomes. It is of great essence to carry out frequent and regular irritation of pulp, a crown conservative technique that using dental care for HR patients. Since HR is a multisystem disease, separating elastic and non-removal tooth structure has been multidisciplinary care is needed. Hence, it is important for dentists recommended [74]. Resulting from the progress in bonding to master the knowledge of various dental manifestations and dentistry and the principle of sealing the wells and grooves of provide optimal treatment options along with other specialists in permanent teeth, pit and ﬁssure sealing using ﬂuid composite pediatric and adult ﬁelds. resin with self-etching bonding system might be a better choice [36]. And it is suggested that all occlusal surfaces, including REFERENCES principal and secondary grooves should be covered [36]. However, 1. Bitzan M, Goodyer PR. Hypophosphatemic Rickets. Pediatr Clin North Am. this preventive approach needs to be reperformed annually 2019;66:179–207. because of the loss or attrition of resin [3]. The self-etching 2. Durmaz E, Zou M, Al-Rijjal RA, Baitei EY, Hammami S, Bircan I, et al. Novel and de bonding system is recommended because of its simple imple- novo PHEX mutations in patients with hypophosphatemic rickets. Bone. mentation and a less aggressive etching on the enamel, avoiding 2013;52:286–91. further damaging the cracks and irritating pulp [36]. 3. Linglart A, Biosse-Duplan M, Briot K, Chaussain C, Esterle L, Guillaume-Czitrom S, Dental abscesses might persist in life, although patients are et al. Therapeutic management of hypophosphatemic rickets from infancy to under conventional and preventive treatment [38]. Endodontic adulthood. Endocr Connect. 2014;3:R13–30. management is necessary to maintain a functional dentition [28]. 4. Francis F, Hennig S, Korn B, Reinhardt R, de Jong P, Poustka A, et al. A gene (PEX) The risk of reinfections is increased due to the altered dentin, even with homologies to endopeptidases is mutated in patients with X-linked hypo- phosphatemic rickets. Nat Genet. 1995;11:130–6. though there is no literature that reports a higher rate of failure in 5. White KE, Evans WE, O'Riordan JLH, Speer MC, Econs MJ, Lorenz-Depiereux B, HR patients [75]. When it comes to the longstanding sinus tract et al. Autosomal dominant hypophosphataemic rickets is associated with and/or periradicular radiolucency after endodontic treatment, mutations in FGF23. Nat Genet. 2000;26:345–8. periradicular curettage might be a choice other than extraction 6. Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, et al. Loss of DMP1 causes rickets [33]. It is still a challenge for post-endodontic coronal restorations. and osteomalacia and identiﬁes a role for osteocytes in mineral metabolism. Nat Some authors choose composite resin to restore the cavities for Genet. 2006;38:1310–5. the little damage of teeth [33, 43]. However, the microleakage in 7. Levy-Litan V, Hershkovitz E, Avizov L, Leventhal N, Bercovich D, Chalifa-Caspi V, the dentin-restoration interfaces might be a risk of reinfection. et al. Autosomal-recessive hypophosphatemic rickets is associated with an Metal crowns are generally recommended for restorations [68]. inactivation mutation in the ENPP1 gene. Am J Hum Genet. 2010;86:273–8. 8. Rafaelsen SH, Raeder H, Fagerheim AK, Knappskog P, Carpenter TO, Johansson S, Meanwhile, the post might increase the risk of root fracture due to et al. Exome sequencing reveals FAM20c mutations associated with ﬁbroblast the thin dentin, which is not recommended [40]. Since the growth factor 23-related hypophosphatemia, dental anomalies, and ectopic adhesive bonding to the unaltered enamel is reliable, all-ceramic calciﬁcation. J Bone Min Res. 2013;28:1378–85. occlusal veneers is advisable [26]. 9. Zhao Y, Yang F, Wang L, Che H. Familial hypophosphatemic rickets caused by a HR patients are susceptible to periodontitis [33, 39, 41]. Period- PHEX gene mutation accompanied by a NPR2 missense mutation. J Pediatr ontitis is an inﬂammatory disease which is initiated by microbial Endocrinol Metab. 2020;33:305–11. plaque and leads to attachment and alveolar bone loss [47]. As 10. Clausmeyer S, Hesse V, Clemens PC, Engelbach M, Kreuzer M, Becker-Rose P, et al. reported, Dmp1-null mice develops severe periodontal defects Mutational analysis of the PHEX gene: novel point mutations and detection of without obvious infection or inﬂammation, while in human the large deletions by MLPA in patients with X-linked hypophosphatemic rickets. Calcif Tissue Int. 2009;85:211–20. percentage of BOP shows no difference between patients and 11. Coyac BR, Hoac B, Chafey P, Falgayrac G, Slimani L, Rowe PS, et al. Defective general population, which indicates that the periodontal defects Mineralization in X-Linked Hypophosphatemia Dental Pulp Cell Cultures. J Dent in patient are different form traditional periodontitis [47, 76]. The Res. 2017;97:184–91. cause of periodontitis in HR patients is probably the reduced and 12. McKee MD, Hoac B, Addison WN, Barros NM, Millan JL, Chaussain C. Extracellular hypoplastic cementum, which is sensitive to disturbances in matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, mineral metabolism and increased attachment loss of PDL [77]. enzymes, and relationship to hypophosphatasia and X-linked hypopho- Thus, conventional management initiated from childhood and sphatemia. Periodontology. 2013;63:102–22. continued during adulthood can prevent the periodontal defects 13. Makitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E. Early treatment to some extent [48]. Decreasing occlusal loads, abandoning improves growth and biochemical and radiographic outcome in X-linked hypo- phosphatemic rickets. J Clin Endocrinol Metab. 2003;88:3591–7. smoking and maintaining a good oral hygiene also play important 14. Chaussain-Miller C, Sinding C, Septier D, Wolikow M, Goldberg M, Garabedian M. roles in preventing periodontal defects [47]. Dentin structure in familial hypophosphatemic rickets: Beneﬁts of vitamin D and It has been found that majority of HR patients have performed phosphate treatment. Oral Dis. 2007;13:482–9. orthodontic treatment [75]. Small dental arches are commonly 15. Rothenbuhler A, Schnabel D, Hogler W, Linglart A. Diagnosis, treatment- seen in HR patients [50]. As reported, there are signiﬁcant monitoring and follow-up of children and adolescents with X-linked hypopho- differences in arch dimensions especially the maxillary between sphatemia (XLH). Metabolism. 2019;103s:153892. HR patients and general population [50]. The different degrees of 16. Emma F, Cappa M, Antoniazzi F, Bianchi ML, Chiodini I, Eller Vainicher C, et al. craniofacial alterations bring about a class III skeletal relationship, X-linked hypophosphatemic rickets: an Italian experts’ opinion survey. Pediatr which appear milder due to the downward and backward position Nephrol. 2019;45:67. 17. Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, et al. of the condyles [78]. And ectopic permanent canines with Clinical practice recommendations for the diagnosis and management of crowded dentition is shown in HR patients [29, 39]. Those X-linked hypophosphataemia. Nat Rev Nephrol. 2019;15:435–55. characteristics combined together lead a major demand for 18. Ovejero D, Gafni RI, Collins MT. 1,25-Dihydroxyvitamin D as Monotherapy for XLH: orthodontic treatment. Meanwhile, conventional treatment makes Back to the Future? J Bone Min Res. 2016;31:925–8. it no longer contraindicate [68]. Implant treatment is also 19. Thabet MA, Truchina O, Chan JC. X-linked hypophosphatemia: Molecular biology acceptable. The successful rate might be increased after conven- and treatment controversies. Acta Paediatrica Sin. 1994;35:180–7. tional treatment [17]. Prolonging the healing time and continuing 20. Rasmussen H, Pechet M, Anast C, Mazur A, Gertner J, Broadus A. Long-term conventional treatment after implant surgery can help to obtain a treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha- better stability of implant [64]. hydroxyvitamin D3. J Pediatr. 1981;99:16–25. BDJ Open (2023) 9:2 X. Jin et al. 21. Chaussain-Miller C, Sinding C, Wolikow M, Lasfargues JJ, Godeau G, Garabedian 48. Biosse Duplan M, Coyac BR, Bardet C, Zadikian C, Rothenbuhler A, Kamenicky P, M. Dental abnormalities in patients with familial hypophosphatemic vitamin et al. Phosphate and Vitamin D Prevent Periodontitis in X-Linked Hypopho- D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D. J sphatemia. J Dent Res. 2016;96:388–95. Pediatr. 2003;142:324–31. 49. Schwartz S, Scriver CR, Reade TM, Shields ED. Oral ﬁndings in patients with 22. Mäkitie O, Kooh S, Sochett E. Prolonged high-dose phosphate treatment: a risk autosomal dominant hypophosphatemic bone disease and X-linked hypopho- factor for tertiary hyperparathyroidism in X-linked hypophosphatemic rickets. sphatemia: further evidence that they are different diseases. Oral Surg Oral Med Clin Endocrinol. 2003;58:163–8. Oral Pathol. 1988;66:310–4. 23. Taylor A, Sherman N, Norman M. Nephrocalcinosis in X-linked hypopho- 50. Al-Jundi SH, Al-Naimy YF, Alsweedan S. Dental arch dimensions in children with sphatemia: Effect of treatment versus disease. Pediatr Nephrol. 1995;9:173–5. hypophosphataemic Vitamin D resistant rickets. Eur Arch Paediatr Dent. 24. Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, et al. A ran- 2010;11:83–7. domized, double-blind, placebo-controlled, phase 3 trial evaluating the efﬁcacy 51. Sh AJ, Am H. Dental Development in Patients with Hypophosphatemia Rickets. of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypopho- Int J Clin Pediatr Dent. 2010;3:1–4. sphatemia: Week 24 Primary Analysis. J Bone Mi Res. 2018;33:1383–93. 52. Hintze H, Wenzel A, Kruhoffer F. Dental hypersensitivity due to hypopho- 25. Souza AP, Kobayashi TY, Lourenco Neto N, Silva SM, Machado MA, Oliveira TM. sphataemia? Dentomaxillofac Radio. 1990;19:81–3. Dental manifestations of patient with vitamin D-resistant rickets. J Appl Oral Sci. 53. Bender IB, Naidorf IJ. Dental observations in vitamin D-resistant rickets with 2013;21:601–6. special reference to periapical lesions. J Endod. 1985;11:514–20. 26. Sabandal MM, Robotta P, Burklein S, Schafer E. Review of the dental implications 54. Gigliotti R, Harrison H, Reveley RA, Drabkowski AJ. Familial vitamin D-refractory of X-linked hypophosphataemic rickets (XLHR). Clin Oral Investig. rickets. J Am Dent Assoc. 1971;82:383–7. 2015;19:759–68. 55. Alexander S, Moloney L, Kilpatrick N. Endodontic management of a patient with 27. Sauk JJ Jr, Witkop CJ Jr. Electron optic analysis of human dentin in hypopho- X-linked hypophosphataemic rickets. Aust Endod J. 2001;27:57–61. sphatemic vitamin D-resistant rickets (report of a kindred with consanguinity). J 56. Rathore R, Nalawade TM, Pateel D, Mallikarjuna R. Oral manifestations of vitamin D Oral Pathol. 1973;2:203–14. resistant rickets in orthopantomogram. BMJ Case Rep. 2013;2013:bcr2012008318. 28. Cohen S, Becker GL. Origin, diagnosis, and treatment of the dental manifestations 57. Hillmann G, Geurtsen W. Pathohistology of undecalciﬁed primary teeth in vitamin of vitamin D-resistant rickets: review of the literature and report of case. J Am D-resistant rickets: review and report of two cases. Oral Surg Oral Med Oral Pathol Dent Assoc. 1976;92:120–9. Oral Radio Endod. 1996;82:218–24. 29. Ainley JE Jr. Manifestations of familial hypophosphatemia. J Endod. 1978;4:26–8. 58. Lyles KW, Burkes EJ Jr, McNamara CR, Harrelson JM, Pickett JP, Drezner MK. The 30. Rakocz M, Keating JR, Johnson R. Management of the primary dentition in vita- concurrence of hypoparathyroidism provides new insights to the pathophysiol- min D-resistant rickets. Oral Surg Oral Med Oral Pathol. 1982;54:166–71. ogy of X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 31. Chadwick BL, Aldred MJ. An unusual giant cell lesion in a child with vitamin 1985;60:711–7. D-resistant rickets. Int J Paediatr Dent. 1992;2:41–5. 59. Abe K, Ooshima T, Lily TS, Yasufuku Y, Sobue S. Structural deformities of decid- 32. Goodman JR, Gelbier MJ, Bennett JH, Winter GB. Dental problems associated with uous teeth in patients with hypophosphatemic vitamin D-resistant rickets. Oral hypophosphataemic vitamin D resistant rickets. Int J Paediatr Dent. 1998;8:19–28. Surg Oral Med Oral Pathol. 1988;65:191–8. 33. Pereira CM, de Andrade CR, Vargas PA, Coletta RD, de Almeida OP, Lopes MA. 60. Daley TD, Jarvis A, Wysocki GP, Kogon SL. X-ray microanalysis of teeth from Dental alterations associated with X-linked hypophosphatemic rickets. J Endod. healthy patients and patients with familial hypophosphatemia. Calcif Tissue Int. 2004;30:241–5. 1990;47:350–5. 34. Batra P, Tejani Z, Mars M. X-linked hypophosphatemia: dental and histologic 61. Nikiforuk G, Fraser D. Chemical determinants of enamel hypoplasia in children ﬁndings. J Can Dent Assoc. 2006;72:69–72. with disorders of calcium and phosphate homeostasis. J Dent Res. 35. Baroncelli GI, Angiolini M, Ninni E, Galli V, Saggese R, Giuca MR. Prevalence and 1979;58:1014–5. pathogenesis of dental and periodontal lesions in children with X-linked hypo- 62. Yuan L, Wu S, Xu H, Xiao J, Yang Z, Xia H, et al. Identiﬁcation of a novel PHEX phosphatemic rickets. Eur J Paediatr Dent. 2006;7:61–6. mutation in a Chinese family with X-linked hypophosphatemic rickets using 36. Douyere D, Joseph C, Gaucher C, Chaussain C, Courson F. Familial hypopho- exome sequencing. Biol Chem. 2015;396:27–33. sphatemic vitamin D-resistant rickets-prevention of spontaneous dental absces- 63. Resnick D. Implant placement and guided tissue regeneration in a patient with ses on primary teeth: a case report. Oral Surg Oral Med Oral Pathol Oral Radio congenital vitamin D-resistant rickets. J Oral Implantol. 1998;24:214–8. Endod. 2009;107:525–30. 64. Friberg B. Branemark system implants and rare disorders: a report of six cases. Int 37. Souza MA, Soares Junior LA, Santos MA, Vaisbich MH. Dental abnormalities and J Periodontics Restor Dent. 2013;33:139–48. oral health in patients with Hypophosphatemic rickets. Clin (Sao Paulo). 65. Shields ED, Scriver CR, Reade T, Fujiwara TM, Morgan K, Ciampi A, et al. X-linked 2010;65:1023–6. hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney. 38. Beltes C, Zachou E. Endodontic management in a patient with vitamin D-resistant Am. J. Hum. Genet. 1990;46:434–42. Rickets. J Endod. 2012;38:255–8. 66. Salmon B, Bardet C, Coyac BR, Baroukh B, Naji J, Rowe PS, et al. Abnormal 39. Rabbani A, Rahmani P, Ziaee V, Ghodoosi S. Dental problems in hypopho- osteopontin and matrix extracellular phosphoglycoprotein localization, and sphatemic rickets, a cross sectional study. Iran J Pediatr. 2012;22:531–4. odontoblast differentiation, in X-linked hypophosphatemic teeth. Connect Tissue 40. Cremonesi I, Nucci C, D’Alessandro G, Alkhamis N, Marchionni S, Piana G. X-linked Res. 2014;55:79–82. hypophosphatemic rickets: Enamel abnormalities and oral clinical ﬁndings. 67. Coyac BR, Falgayrac G, Baroukh B, Slimani L, Sadoine J, Penel G, et al. Tissue- Scanning. 2014;36:456–61. speciﬁc mineralization defects in the periodontium of the Hyp mouse model of 41. Ayesha Thabusum D, Stinton NM, Uston KA, Davis CD. Hypophosphatemic rickets X-linked hypophosphatemia. Bone. 2017;103:334–46. and pre-eruptive spontaneous dental abscess. Case Rep Dent. 2016;83:46–50. 68. Opsahl Vital S, Gaucher C, Bardet C, Rowe PS, George A, Linglart A, et al. Tooth 42. Paredes SEY, Segato RAB, Moreira LD, Moreira A, Serrano K, Rodrigues CT, et al. dentin defects reﬂect genetic disorders affecting bone mineralization. Bone. Dentoalveolar abscesses not associated with caries or trauma: A diagnostic 2012;50:989–97. hallmark of hypophosphatemic rickets initially misdiagnosed as hypochon- 69. Connor J, Olear EA, Insogna KL, Katz L, Baker S, Kaur R, et al. Conventional droplasia. Head Neck Pathol. 2017;12:604–9. Therapy in Adults With X-Linked Hypophosphatemia: Effects on enthesopathy 43. Murayama T, Iwatsubo R, Akiyama S, Amano A, Morisaki I. Familial hypopho- and dental disease. J Clin Endocrinol Metab. 2015;100:3625–32. sphatemic vitamin D-resistant rickets: dental ﬁndings and histologic study of 70. Wang X, Wang J, Liu Y, Yuan B, Ruest LB, Feng JQ, et al. The speciﬁc role of teeth. Oral Surg Oral Med Oral Pathol Oral Radio Endod. 2000;90:310–6. FAM20C in dentinogenesis. J Dent Res. 2015;94:330–6. 44. Soares EC, Costa FW, Ribeiro TR, Alves AP, Fonteles CS. Clinical approach in 71. Rangiani A, Cao ZG, Liu Y, Voisey Rodgers A, Jiang Y, Qin CL, et al. Dentin matrix familial hypophosphatemic rickets: report of three generations. Spec Care Dent. protein 1 and phosphate homeostasis are critical for postnatal pulp, dentin and 2013;33:304–7. enamel formation. Int J Oral Sci. 2012;4:189–95. 45. Andersen MG, Beck-Nielsen SS, Haubek D, Hintze H, Gjorup H, Poulsen S. Peria- 72. Boukpessi T, Hoac B, Coyac BR, Leger T, Garcia C, Wicart P, et al. Osteopontin and pical and endodontic status of permanent teeth in patients with hypopho- the dento-osseous pathobiology of X-linked hypophosphatemia. Bone. sphatemic rickets. J Oral Rehabil. 2012;39:144–50. 2017;95:151–61. 46. Al-Jundi SH, Hammad MM, Dabous I. Case report: hypophosphatemic rickets and 73. Coyac BR, Falgayrac G, Penel G, Schmitt A, Schinke T, Linglart A, et al. Impaired aggressive periodontitis: a review of the role of dentine matrix protein 1 in the mineral quality in dentin in X-linked hypophosphatemia. Connect Tissue Res. pathogenesis. Eur Arch Paediatr Dent. 2011;12:46–50. 2018;59:91–6. 47. Ye L, Liu R, White N, Alon US, Cobb CM. Periodontal status of patients with 74. Seow WK. Diagnosis and management of unusual dental abscesses in children. hypophosphatemic rickets: a case series. J Periodontol. 2011;82:1530–5. Aust Dent J. 2003;48:156–68. BDJ Open (2023) 9:2 X. Jin et al. 75. Hanisch M, Bohner L, Sabandal MMI, Kleinheinz J, Jung S. Oral symptoms and oral wouldbeusedfor research purposes andphotographs wouldbe publishedinthis health-related quality of life of individuals with x-linked hypophosphatemia. way. This study was approved by the Institutional Ethic Board of the Afﬁliated Head Face Med. 2019;15:8. Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China 76. Ye L, Zhang S, Ke H, Bonewald LF, Feng JQ. Periodontal breakdown in the Dmp1 (No. 2020-16). null mouse model of hypophosphatemic rickets. J Dent Res. 2008;87:624–9. 77. Zhang H, Chavez MB, Kolli TN, Tan MH, Fong H, Chu EY, et al. Dentoalveolar defects in the Hyp Mouse Model of X-linked Hypophosphatemia. Physiol Rep. ADDITIONAL INFORMATION 2020;99:419–28. Correspondence and requests for materials should be addressed to Baiping Fu. 78. Al-Jundi SH, Dabous IM, Al-Jamal GA. Craniofacial morphology in patients with hypophosphataemic vitamin-D-resistant rickets: A cephalometric study. J Oral Reprints and permission information is available at http://www.nature.com/ Rehabil. 2009;36:483–90. reprints Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims ACKNOWLEDGEMENTS in published maps and institutional afﬁliations. This work was supported by National Natural Science Foundation of China (81970982). XJ and YX contributed equally to this work and should be considered as co-ﬁrst authors. 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DOI: 10.1038/s41405-023-00129-9
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Abstract

www.nature.com/bdjopen ARTICLE OPEN Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature 1 2 2 2 2 2 2 2 Xinyang Jin , Yuedan Xu , Wei Liu , Zhiwei Shi , Yi Sun , Xinni Pan , Ling Zhang and Baiping Fu © The Author(s) 2023 BACKGROUND: The treatment and management of patients suffering from hypophosphatemic rickets (HR) remain a major challenge for dental practitioners and affected patients. OBJECTIVES: To report a case of HR presenting with speciﬁc dental ﬁndings and to review the dental manifestations and treatment of HR patients. METHODS: Case: A 32-year-old male presented with multiple dental abscesses and short stature. A thorough history was taken followed by clinical oral examination, and relevant radiological investigation was done. Literature research: In 2020, electronic literature searches were carried out in PubMed and complemented by a careful assessment of the reference lists of the identiﬁed relevant papers. Articles and reports fulﬁlled the inclusion criteria: indexed reviews, case series and case reports in English and restricted to human studies were considered. RESULTS: The intraoral examination revealed multiple dental abscesses and general periodontal disease; the radiographic examination showed poorly deﬁned lamina dura, large pulp chambers and periapical lesions. Based on the contents of the 43 articles identiﬁed in the search, the current knowledge of dental manifestations, treatment and management of HR was summarized. CONCLUSIONS: As HR is a multisystem disease, multidisciplinary care is needed. By summarizing current evidences, we proposed an evidence-based dental management and provided recommendations on diagnosis and treatment of the disease.It is of profound clinical signiﬁcance to acquire knowledge of the dental manifestations and provide optimal treatment options for patients. BDJ Open (2023) 9:2 ; https://doi.org/10.1038/s41405-023-00129-9 INTRODUCTION PHEX, mainly expressed in osteocytes and odontoblasts, is located Hypophosphatemic rickets (HR) is a group of hereditary metabolic on chromosome Xp22.1 and encodes for an endopeptidase [10]. bone diseases caused by renal phosphate wasting, which has no Inactivating PHEX mutations contribute to the increasing secretion response of high doses of vitamin D [1]. HR is characterized of FGF23 [11]. As a key circulating factor that directs sodium- by short stature, delayed walking, bow legs, bone/joint pain, dependent phosphate transporters in the kidney and intestine, spontaneous dental abscess, hypophosphatemia, and inappropri- the high level FGF23 results in impaired proximal renal phosphate ately normal serum 1,25(OH) D level [2]. Genetic defects in factors reabsorption, causing hypophosphatemia and systemic regulation necessary for phosphate handling is the main cause of phosphate of mineralization [12]. Meanwhile, the PHEX mutations contribute wasting [3]. HR can be mainly divided into three types, including to the local accumulation of mineralization inhibitors such as OPN X-linked hypophosphatemic rickets (XLHR) due to a loss function (osteopontin) and ASARM (the acidic serine- and aspartate-rich of phosphate regulating gene with homologies to endopeptidases motif) peptides at the level of the extracellular matrix [12]. on the X chromosome (PHEX) [4], autosomal dominant hypopho- Likewise, the certain genetic mutation emphasizes the importance sphatemic rickets (ADHR) caused by mutation in the ﬁbroblast of FGF23 and DMP1 in the pathogenesis of ADHR and ARHR, growth factor 23 (FGF23) gene [5] and autosomal recessive respectively [5, 6]. As the same result of phosphate wasting, it is hypophosphatemic rickets (ARHR) as a result of mutation in dentin found that different types of HR cause similar, though not matrix protein 1 (DMP1) gene, ecto-nucleotide pyrophos- phatase/ identical, clinical and radiographical parameters, which mostly phosphodiesterase 1 (ENNP1) gene, or family with sequence depend on the duration of hypophosphatemia [1]. similarity 20, member C (FAM20C) [6–8]. Early diagnosis of HR is of great signiﬁcance, since early XLHR, also named as vitamin D resistant rickets, familial treatment promotes growth, reduces bone pain and improves hypophosphatemic rickets, or phosphate diabetes, is the most dental health [13, 14]. The diagnosis of HR is on the basis of common form of HR, with an incidence of around 1:20000 [9]. combination of clinical, radiological and biochemical ﬁndings. 1 2 Department of Stomatology, The Fourth Afﬁliated Hospital, Zhejiang University School of Medicine, Yiwu, China. Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China. email: fbp@zju.edu.cn Received: 31 October 2022 Revised: 29 December 2022 Accepted: 2 January 2023 1234567890();,: X. Jin et al. Fig. 1 Intraoral views and panoramic radiograph of a 32-year-old male patient with HR. Intraoral views (a–e) showed multiple ﬁstulas and abscesses, malocclusion, and dental attrition in the left lower incisors; Panoramic radiograph (f) revealed enlarged pulp chambers, the radiolucencies at periapical regions of teeth # 12, 13, 17, 22, 23, 32, 36, 37, 41, 42, 43 and 48, and the presence of endodontically treated teeth # 12, 13, 23 and 32. Clinically, patients of HR feature leg bowing, delayed walking, provide timely treatment options, which does help to improve the waddling gait, bone/joint pain, short stature and dental abscesses quality of HR patients’ life [26]. This article aimed at reporting a [2]. Especially, any form of leg bowing and widening of the case of male with HR, reviewing the dental manifestations and metaphysis acquire a further radiological and biomedical exam- treatment of HR patients and providing suggestions of dental ination [15]. Radiographic manifestations show the long bone management. deformities and abnormal growth plates with widened and frayed metaphyses [15]. Biomedical criteria for the diagnosis of HR includes serum phosphate below the normal threshold for age, CASE REPORT elevated alkaline phosphatase, normal or upper normal parathyr- A 32-year-old male was referred to the Department of Prosthodon- oid hormone levels, normal serum calcium, and low urinary tics with the complaint of “several abscesses that appeared in the calcium excretion [16]. In addition, a family history of the disease is mouth”. The patient was diagnosed with HR at the age of 2, but his beneﬁt for diagnosis due to an X-linked dominant inheritance parents didn’t have metabolic disorder. Since been diagnosed, he pattern of PHEX mutation. Genetic analysis, which identiﬁes was treated with oral phosphate supplementation, calcitriol and mutations in the PHEX gene in about 70% of patients with HR, is vitamin D2. In addition, he was undergoing pharmaceutical therapy the ﬁnal conﬁrmation [15]. If genetic analysis is not available, with burosumab at a dose of 60 mg/month by hypodermic injection elevated plasma levels of intact FGF23 supports the diagnosis [17]. at the age of 31. Treatment initiation is recommended as soon as diagnosis is On physical examination, the patient showed short stature, bow established [17]. Conventional treatment with oral phosphate legs, achilles tendinitis and mild hearing loss. The intraoral supplements and active vitamin D (calcitriol or alfacalcidol), has examination revealed multiple ﬁstulas and abscesses at the been proposed for decades [3, 18, 19]. This kind of therapy has periapical regions of maxillary right lateral incisor, mandibular left been shown to result in the positive outcomes of decrease in bone lateral incisor and ﬁrst molar, and mandibular right central incisor pain, normalization of alkaline phosphatase level, increase in (Fig. 1a–e). The pulpal vitality test was negative at maxillary right growth velocity, straightening of legs and improving dental lateral incisor, maxillary right canine and second molar, mandibular mineralization [3, 13, 20, 21]. However, due to the limitations, such left canine, mandibular left lateral incisor and ﬁrst molar, and as increasing risk of nephrocalcinosis, urolithiasis or hyperpar- mandibular right central incisor and third molar. Periodontal athyroidism, the dose of phosphate supplements and vitamin D examination revealed the absence of many teeth, and general analogues should be strictly controlled according to individual periodontal disease resulting in some teeth increased probing situation [22, 23]. Recently, a novel therapy with burosumab, a pocket depth of 10 mm or more. Radiographic examination in Fig. 1f kind of humanized monoclonal anti-FGF23 antibody, has been showed poorly deﬁned lamina dura and enlarged pulp chambers approved for the treatment of XLHR patients over 1 year of age in and radicular canals. Radiolucencies were detected at periapical Europe and US, with the function of increasing renal phosphate regions of maxillary right lateral incisor, maxillary right canine and reabsorption and normalizing serum phosphate [15, 24]. Never- second molar, mandibular left lateral incisor and canine, mandibular theless, all of those therapies focus on regulation of systemic left lateral incisor, mandibular left second and third molar, serum phosphate, the defects in mineral quality and quantity mandibular right central and lateral incisor, and mandibular right during formation of mineralized tissues such as tooth and bone canine and third molar. Several teeth (i.e., maxillary right lateral due to the local dysfunction of PHEX intend to be treated [11]. incisor and canine, maxillary left canine, and mandibular left lateral Given that, the disease follow-up and treatment management are incisor) had received endodontic treatment before. essential. For some patients, dental manifestations might be the ﬁrst symptom diagnosed [25]. Furthermore, early prophylaxis and LITERATURE SEARCH treatment can improve dental status [14]. Hence, broadening A literature search was carried out to identify all cases of HR knowledge of various dental manifestations of HR is required to associated dental manifestations. The PubMed database was BDJ Open (2023) 9:2 X. Jin et al. Table 1. Number of reported cases of hypophosphatemic rickets with dental manifestations. Author Year No. of cases Author Year No. of cases Gigliotti et al. [54] 1971 3 Baroncelli et al. [35] 2006 9 Sauk et al. [27] 1973 1 Chaussain-Miller et al. [14] 2007 7 Cohen et al. [28] 1976 1 Douyere et al. [36] 2009 1 Ainley et al. [29] 1978 1 Souza et al. [37] 2010 14 Nikiforuk et al. [61] 1979 26 Al-Jundi et al. [50] 2010 21 Rakocz et al. [30] 1982 1 Sh AJ et al. [51] 2010 21 Lyles et al. [58] 1985 1 Al-Jundi et al. [46] 2011 1 Bender et al. [53] 1985 50 Ye et al. [47] 2011 10 Abe et al. [59] 1988 3 Beltes et al. [38] 2012 1 Schwartz et al. [49] 1988 18 Rabbani et al. [39] 2012 19 Daley et al. [60] 1990 3 Andersen et al. [45] 2012 52 Hintze et al. [52] 1990 1 Soares et al. [44] 2013 3 Shields et al. [65] 1990 17 Rathore et al. [56] 2013 1 Chadwick et al. [31] 1992 1 Friberg et al. [64] 2013 3 Hillmann et al. [57] 1996 2 Souza et al. [25] 2013 1 Goodman et al. [32] 1998 17 McKee et al. [12] 2013 1 Resnick et al. [63] 1998 1 Cremonesi et al. [40] 2014 10 Murayama et al. [43] 2000 1 Yuan et al. [62] 2015 4 Alexander et al. [55] 2001 1 Ayesha et al. [41] 2016 1 Chaussain-Miller et al. [21] 2003 48 Biosse et al. [48] 2016 34 Pereira et al. [33] 2004 3 Paredes et al. [42] 2017 1 Batra et al. [34] 2006 1 Total cases reported 416 searched until 10 March 2020 with the following MESH term: characteristics of HR [25, 27, 32, 41, 44, 46–48, 53, 54]. “Rickets, Hypophosphatemic” and a keyword: “dental”.Itwas Other common manifestations are thinner enamel and dentin supplemented by manual searches in the reference lists of [21, 30, 40, 53], primary tooth resorption [44, 56] and short root relevant articles. The search retrieved 198 results. Articles and [43, 57]. reports including indexed reviews, case series and case reports Histopathologically, hypomineralized dentin, featured by a published in English and in peer-reviewed journals were widened predentin with fewer well-deﬁned dentinal tubules and considered, and restricted to human studies. After screening numerous unmerged calcospherites creating interglobular spaces, is the title and abstract, 43 relevant full-length articles were commonly seen in teeth of HR patients, while the mantle dentin is included. This search identiﬁed about 416 reported cases unaffected [12, 14, 21, 30–32, 37, 40, 52, 53, 55–60]. The organization [12, 14, 21, 25, 27–65], as presented in Table 1. and polarization of odontoblasts are also impaired [66]. Enamel alternation, such as numerous crater-shaped depressions and deep microcleavages penetrating into the enamel thickness, can be seen DENTAL MANIFESTATION in some patients [21, 32, 35, 37, 39, 49, 58, 61, 62]. Due to the dentin Clinically, recurrent spontaneous dental abscesses both in primary and enamel alternation, bacteria can invade easily from the oral and permanent dentition without carries, periodontal problems, cavity to the dental pulp, causing pulp necrosis in caries-free tooth traumatic injuries or restorations are common ﬁndings in HR [39]. Cementum is thinner, with roughly granular with hypominer- patients [12, 14, 21, 25, 27–44]. Meanwhile, with the increasing alized interglobular patterns [48, 67]. age, the number of endodontically affected teeth signiﬁcantly rises, and the incisors and canines usually get affected prior to molars and premolars [45]. HR patients are more prone to suffer DENTAL TREATMENT periodontal bone loss than the general population, while the Prophylaxis percentage of BOP seems to be similar without commensurate Preventing bacteria invading dentin and pulp is important to increase [33, 39, 41, 46–48]. Another main dental ﬁnding is the reduce dental abscesses [17]. Stainless steel crown was used to smaller dental arches which always accompany with crowded cover the crown of primary molar in the past [30, 55]. However, dentition and class III occlusion [29, 46, 49, 50]. Other infrequent the limitations of large pulp chamber, high pulp horn, thin enamel dental ﬁndings are ectopic permanent canines [34], delayed and hypomineralized dentin should be taken into strict considera- eruption of both primary and permanent teeth [39], delayed tion. Sealing occlusal surfaces of primary and permanent teeth dental development [41, 51] and dental hypersensitivity [52]. with composite resin is suggested, the properties of which have Radiologically, both primary and permanent teeth exhibit greatly improved over the last decade [26, 68]. It is worth noting enlarged pulp chambers with high pulp horns which sometimes that self-etch adhesive system is recommended to minimize risk of extend up to or beyond the dentino-enamel junction pulp irritation, and the sealing must be repeated every year due to [12, 21, 27, 29, 30, 32–34, 37, 39–45, 49, 52–56]. Zones of gradual wear of the resin [3]. The early monitored use of topical hypomineralized early forming coronal dentin appear as a “halo” applications of ﬂuoride is critical for preventing subsequent at the dentino-enamel junction around the circumpulpal dentin serious dental infections [33, 36–39, 42]. Tooth attrition is easier to [52, 55]. Hypoplastic alveolar ridge, reduced radiopacity of lamina be seen in HR patients for the enamel alternation, so a nightguard dura and varying degree of alveolar bone loss are also radiological acrylic splint is also suggested [53, 55]. BDJ Open (2023) 9:2 X. Jin et al. Endodontic treatment enlarged pulp chambers, periapical bone loss and pulp necrosis For the endodontically affected teeth, root canal treatment is [17]. (5) In adults, it is suggested to perform conventional the conventional choice, while extraction is necessary for those supportive periodontal therapy, including periodontal risk assess- of abscesses spread quickly in jaw bone especially in primary ment as well as supragingival and subgingival debridement twice teeth [3]. The procedures of endodontic treatment should try to a year if necessary [17]. (6) If orthodontic and implant treatment be sterile. Using sodium hypochlorite to irrigate canals and are required, it must be based on the premise that conventional Ca(OH) as intracanal medicament for a 10-day interval is therapy is correctly treated [26, 63, 64]. recommended, and the determination of working length is preferred to combine electronic apex locators and radiograph [38]. Avoiding any voids and achieving the best possible density DISCUSSION of the root canal ﬁlling are the goal of the obturation of the root HR is genetic disorders, whose main symptoms are hypominer- canal system [26]. Meanwhile, the ﬁlling of root canal might be alized skeleton and dentition [12]. Dental abscesses without caries suggested using thermoplasticized obturation techniques with a are observed most frequently in HR, even in some cases as the ﬁrst virtually insoluble sealer [26]. Apical curettage procedure and symptom diagnosed [25]. In the present report (Fig. 1), the apical barriers with mineral trioxide aggregate might be symptoms were enlarged pulp chambers and multiple dental performed in sever abscessesand open apical foramens, abscesses. The cause of dental abscesses is the enamel alternation respectively [28, 33]. and hypomineralized dentin [39]. However, the relationship between HR and hypomineralized dentin remains unclear. In the Prosthodontic treatment past, hypophosphatemia was thought to be responsible for For some mild or moderate damages, adhesive procedures can be dysplastic and poorly mineralized circumpulpal dentin with wide used, but in sever situation, such as dominant enamel fracturing areas of interglobular dentin, which limited growth and fusion of and rapid dental wear, full coverage restoration should be chosen calcospherites [69]. Recent researches have shown that the [68]. Regarding to the coronal restoration of endodontic treatment mineralization induced by human cells is disturbed independently teeth, occlusal coverage with ﬁtted stainless steel crowns is of hypophosphatemia and supported a local role for PHEX, DMP1 suggested to protect teeth from recurrent infections, however, or FAM20C in matrix mineralization [11, 70, 71]. This ﬁnding might posts cannot be supported due to the thin dentin [40, 55]. As for illustrate that conventional therapy improve dental complications the ceramic crown, it is not recommended for teeth with but not prevent [35]. Due to different mechanisms of three forms prominent pulp horns, since the preparation costs a greater loss of HR, the article mainly focused on XLHR. Several studies have of dentin than metal crown [26]. Therefore, all-ceramic occlusal conﬁrmed that PHEX regulates the mineralization of the veneer might be another choice not only as a minimal invasive extracellular matrix at the local level in mineralized bone and approach but for aesthetic reason [26]. dentin and maintains mineralized matrix homeostasis by cleaving of acidic, non-collagenous SIBLING proteins and peptides of the Periodontal treatment extracellular matrix such as OPN, MEPE (matrix extracellular Conventional supportive periodontal therapy is of great beneﬁt phosphoglycoprotein) and ARARM [66, 72, 73]. Furthermore, it is for HR patients [3]. Hence, twice-yearly visits to perform suggested that OPN and MEPE inhibit tooth mineralization conventional supportive periodontal therapy aimed to decrease through different ways, with OPN acting at the mineralized gingival inﬂammation and suppress periodontal pockets for adults calcospherites and MEPE at the region of the unmineralized is suggested [17]. interglobular dentin [66]. From the literature review (Table 1), we can ﬁnd that the Orthodontic treatment majority of reported patients are females, which seems to indicate Although it is conﬁrmed that the periodontium of HR patients is a higher HR prevalence in female. However, male patients are less prone to orthodontic treatment [67], orthodontic treatment is usually shown severer dental complications, such as taurodontism not contraindicated especially for those treated with conventional [69]. Since most cases are determined by PHEX, an X-linked systemic treatment, and could trigger extensive remodeling of the dominant mutant gene, it might be a gene dose effect [32]. The alveolar bone [68]. severity of complications might depend on three factors, including family history, medical history and age. Patients born to affected Implant treatment mother are inclined to bear poorer dental status for primary Implants are acceptable for HR patients and several successful dentition than those born to healthy mother, due to the lower cases have been reported [63, 64]. However, the successful rate is phosphate and vitamin D obtained from the affected mother declined in those who are not under conventional treatment, during fetal odontogenesis [21]. Nevertheless, a family history hence, implant surgery is recommended to be performed after 3-6 contributes to an earlier diagnosis of HR, which might take an months of conventional treatment, which should be continued for earlier treatment for patients, resulting a better outcome for 6 months following implant surgery [17]. It might be better permanent dentition [15]. Although conventional treatment is not to prolong the healing time up to 6 months to obtain a good able to prevent oral complications, its beneﬁcial effects on dental stability [64]. and periodontal tissues cannot be underestimated [35]. It has already been conﬁrmed that conventional treatment for HR patients improves mineralization of dentin and decreases the DENTAL MANAGEMENT incidence of endodontic infection in children [14, 21]. Meanwhile, In summary, the lifetime dental management for a particular the beneﬁt of continuing treatment for adults has been proved in patient is as followed. (1) Once the diagnosis is established, the permanent teeth and periodontal health recent years [48]. conventional treatment should be initiated and last a lifetime if However, the dose of medicine should depend on the age and possible [17]. (2) The dental examination should be performed stage of development, for excessive phosphate might result in twice a year regularly for adults and children, including dental hyperparathyroidism [17]. The number of endodontically affected orthopantomogram, of which the ﬁrst time is suggested at age 5 teeth raises signiﬁcantly with age, due to the exposure of [17, 68]. (3) Typical ﬂuoride application and pit and ﬁssure sealing defective dentin [45]. Thus, only incisors or canines are affected both in primary and permanent teeth should be carried out as in younger patients and affected posterior teeth are more soon as acquired [40, 42]. (4) We recommend a thorough dental commonly seen in older patients [45]. Similar situation is present examination clinically and radiologically searching for all of the in the case report (Fig. 1). BDJ Open (2023) 9:2 X. Jin et al. In order to decrease the risk of dental abscess, preventive CONCLUSION approaches, such as topical ﬂuoride application, pit and ﬁssure HR is associated with marked dental manifestations and patients sealing, stainless steel crown and nightguard acrylic splint are with them exhibit a tendency of poorer quality of life. Early proposed for decades [30, 33, 55]. As the using of conventional diagnosis, treatment and management are the keys to successful steel crown requires tooth preparation which might cause the outcomes. It is of great essence to carry out frequent and regular irritation of pulp, a crown conservative technique that using dental care for HR patients. Since HR is a multisystem disease, separating elastic and non-removal tooth structure has been multidisciplinary care is needed. Hence, it is important for dentists recommended [74]. Resulting from the progress in bonding to master the knowledge of various dental manifestations and dentistry and the principle of sealing the wells and grooves of provide optimal treatment options along with other specialists in permanent teeth, pit and ﬁssure sealing using ﬂuid composite pediatric and adult ﬁelds. resin with self-etching bonding system might be a better choice [36]. And it is suggested that all occlusal surfaces, including REFERENCES principal and secondary grooves should be covered [36]. However, 1. Bitzan M, Goodyer PR. Hypophosphatemic Rickets. Pediatr Clin North Am. this preventive approach needs to be reperformed annually 2019;66:179–207. because of the loss or attrition of resin [3]. The self-etching 2. Durmaz E, Zou M, Al-Rijjal RA, Baitei EY, Hammami S, Bircan I, et al. Novel and de bonding system is recommended because of its simple imple- novo PHEX mutations in patients with hypophosphatemic rickets. Bone. mentation and a less aggressive etching on the enamel, avoiding 2013;52:286–91. further damaging the cracks and irritating pulp [36]. 3. Linglart A, Biosse-Duplan M, Briot K, Chaussain C, Esterle L, Guillaume-Czitrom S, Dental abscesses might persist in life, although patients are et al. Therapeutic management of hypophosphatemic rickets from infancy to under conventional and preventive treatment [38]. Endodontic adulthood. Endocr Connect. 2014;3:R13–30. management is necessary to maintain a functional dentition [28]. 4. Francis F, Hennig S, Korn B, Reinhardt R, de Jong P, Poustka A, et al. A gene (PEX) The risk of reinfections is increased due to the altered dentin, even with homologies to endopeptidases is mutated in patients with X-linked hypo- phosphatemic rickets. Nat Genet. 1995;11:130–6. though there is no literature that reports a higher rate of failure in 5. White KE, Evans WE, O'Riordan JLH, Speer MC, Econs MJ, Lorenz-Depiereux B, HR patients [75]. When it comes to the longstanding sinus tract et al. Autosomal dominant hypophosphataemic rickets is associated with and/or periradicular radiolucency after endodontic treatment, mutations in FGF23. Nat Genet. 2000;26:345–8. periradicular curettage might be a choice other than extraction 6. Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, et al. Loss of DMP1 causes rickets [33]. It is still a challenge for post-endodontic coronal restorations. and osteomalacia and identiﬁes a role for osteocytes in mineral metabolism. Nat Some authors choose composite resin to restore the cavities for Genet. 2006;38:1310–5. the little damage of teeth [33, 43]. However, the microleakage in 7. Levy-Litan V, Hershkovitz E, Avizov L, Leventhal N, Bercovich D, Chalifa-Caspi V, the dentin-restoration interfaces might be a risk of reinfection. et al. Autosomal-recessive hypophosphatemic rickets is associated with an Metal crowns are generally recommended for restorations [68]. inactivation mutation in the ENPP1 gene. Am J Hum Genet. 2010;86:273–8. 8. Rafaelsen SH, Raeder H, Fagerheim AK, Knappskog P, Carpenter TO, Johansson S, Meanwhile, the post might increase the risk of root fracture due to et al. Exome sequencing reveals FAM20c mutations associated with ﬁbroblast the thin dentin, which is not recommended [40]. Since the growth factor 23-related hypophosphatemia, dental anomalies, and ectopic adhesive bonding to the unaltered enamel is reliable, all-ceramic calciﬁcation. J Bone Min Res. 2013;28:1378–85. occlusal veneers is advisable [26]. 9. Zhao Y, Yang F, Wang L, Che H. Familial hypophosphatemic rickets caused by a HR patients are susceptible to periodontitis [33, 39, 41]. Period- PHEX gene mutation accompanied by a NPR2 missense mutation. J Pediatr ontitis is an inﬂammatory disease which is initiated by microbial Endocrinol Metab. 2020;33:305–11. plaque and leads to attachment and alveolar bone loss [47]. As 10. Clausmeyer S, Hesse V, Clemens PC, Engelbach M, Kreuzer M, Becker-Rose P, et al. reported, Dmp1-null mice develops severe periodontal defects Mutational analysis of the PHEX gene: novel point mutations and detection of without obvious infection or inﬂammation, while in human the large deletions by MLPA in patients with X-linked hypophosphatemic rickets. Calcif Tissue Int. 2009;85:211–20. percentage of BOP shows no difference between patients and 11. Coyac BR, Hoac B, Chafey P, Falgayrac G, Slimani L, Rowe PS, et al. Defective general population, which indicates that the periodontal defects Mineralization in X-Linked Hypophosphatemia Dental Pulp Cell Cultures. J Dent in patient are different form traditional periodontitis [47, 76]. The Res. 2017;97:184–91. cause of periodontitis in HR patients is probably the reduced and 12. McKee MD, Hoac B, Addison WN, Barros NM, Millan JL, Chaussain C. Extracellular hypoplastic cementum, which is sensitive to disturbances in matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, mineral metabolism and increased attachment loss of PDL [77]. enzymes, and relationship to hypophosphatasia and X-linked hypopho- Thus, conventional management initiated from childhood and sphatemia. Periodontology. 2013;63:102–22. continued during adulthood can prevent the periodontal defects 13. Makitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E. Early treatment to some extent [48]. Decreasing occlusal loads, abandoning improves growth and biochemical and radiographic outcome in X-linked hypo- phosphatemic rickets. J Clin Endocrinol Metab. 2003;88:3591–7. smoking and maintaining a good oral hygiene also play important 14. Chaussain-Miller C, Sinding C, Septier D, Wolikow M, Goldberg M, Garabedian M. roles in preventing periodontal defects [47]. Dentin structure in familial hypophosphatemic rickets: Beneﬁts of vitamin D and It has been found that majority of HR patients have performed phosphate treatment. Oral Dis. 2007;13:482–9. orthodontic treatment [75]. Small dental arches are commonly 15. Rothenbuhler A, Schnabel D, Hogler W, Linglart A. Diagnosis, treatment- seen in HR patients [50]. As reported, there are signiﬁcant monitoring and follow-up of children and adolescents with X-linked hypopho- differences in arch dimensions especially the maxillary between sphatemia (XLH). Metabolism. 2019;103s:153892. HR patients and general population [50]. The different degrees of 16. Emma F, Cappa M, Antoniazzi F, Bianchi ML, Chiodini I, Eller Vainicher C, et al. craniofacial alterations bring about a class III skeletal relationship, X-linked hypophosphatemic rickets: an Italian experts’ opinion survey. Pediatr which appear milder due to the downward and backward position Nephrol. 2019;45:67. 17. Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, et al. of the condyles [78]. And ectopic permanent canines with Clinical practice recommendations for the diagnosis and management of crowded dentition is shown in HR patients [29, 39]. Those X-linked hypophosphataemia. Nat Rev Nephrol. 2019;15:435–55. characteristics combined together lead a major demand for 18. Ovejero D, Gafni RI, Collins MT. 1,25-Dihydroxyvitamin D as Monotherapy for XLH: orthodontic treatment. Meanwhile, conventional treatment makes Back to the Future? J Bone Min Res. 2016;31:925–8. it no longer contraindicate [68]. Implant treatment is also 19. Thabet MA, Truchina O, Chan JC. X-linked hypophosphatemia: Molecular biology acceptable. The successful rate might be increased after conven- and treatment controversies. Acta Paediatrica Sin. 1994;35:180–7. tional treatment [17]. Prolonging the healing time and continuing 20. Rasmussen H, Pechet M, Anast C, Mazur A, Gertner J, Broadus A. Long-term conventional treatment after implant surgery can help to obtain a treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha- better stability of implant [64]. hydroxyvitamin D3. J Pediatr. 1981;99:16–25. BDJ Open (2023) 9:2 X. Jin et al. 21. Chaussain-Miller C, Sinding C, Wolikow M, Lasfargues JJ, Godeau G, Garabedian 48. Biosse Duplan M, Coyac BR, Bardet C, Zadikian C, Rothenbuhler A, Kamenicky P, M. Dental abnormalities in patients with familial hypophosphatemic vitamin et al. Phosphate and Vitamin D Prevent Periodontitis in X-Linked Hypopho- D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D. J sphatemia. J Dent Res. 2016;96:388–95. Pediatr. 2003;142:324–31. 49. Schwartz S, Scriver CR, Reade TM, Shields ED. Oral ﬁndings in patients with 22. Mäkitie O, Kooh S, Sochett E. Prolonged high-dose phosphate treatment: a risk autosomal dominant hypophosphatemic bone disease and X-linked hypopho- factor for tertiary hyperparathyroidism in X-linked hypophosphatemic rickets. sphatemia: further evidence that they are different diseases. Oral Surg Oral Med Clin Endocrinol. 2003;58:163–8. Oral Pathol. 1988;66:310–4. 23. Taylor A, Sherman N, Norman M. Nephrocalcinosis in X-linked hypopho- 50. Al-Jundi SH, Al-Naimy YF, Alsweedan S. Dental arch dimensions in children with sphatemia: Effect of treatment versus disease. Pediatr Nephrol. 1995;9:173–5. hypophosphataemic Vitamin D resistant rickets. Eur Arch Paediatr Dent. 24. Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, et al. A ran- 2010;11:83–7. domized, double-blind, placebo-controlled, phase 3 trial evaluating the efﬁcacy 51. Sh AJ, Am H. Dental Development in Patients with Hypophosphatemia Rickets. of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypopho- Int J Clin Pediatr Dent. 2010;3:1–4. sphatemia: Week 24 Primary Analysis. J Bone Mi Res. 2018;33:1383–93. 52. Hintze H, Wenzel A, Kruhoffer F. Dental hypersensitivity due to hypopho- 25. Souza AP, Kobayashi TY, Lourenco Neto N, Silva SM, Machado MA, Oliveira TM. sphataemia? Dentomaxillofac Radio. 1990;19:81–3. Dental manifestations of patient with vitamin D-resistant rickets. J Appl Oral Sci. 53. Bender IB, Naidorf IJ. Dental observations in vitamin D-resistant rickets with 2013;21:601–6. special reference to periapical lesions. J Endod. 1985;11:514–20. 26. Sabandal MM, Robotta P, Burklein S, Schafer E. Review of the dental implications 54. Gigliotti R, Harrison H, Reveley RA, Drabkowski AJ. Familial vitamin D-refractory of X-linked hypophosphataemic rickets (XLHR). Clin Oral Investig. rickets. J Am Dent Assoc. 1971;82:383–7. 2015;19:759–68. 55. Alexander S, Moloney L, Kilpatrick N. Endodontic management of a patient with 27. Sauk JJ Jr, Witkop CJ Jr. Electron optic analysis of human dentin in hypopho- X-linked hypophosphataemic rickets. Aust Endod J. 2001;27:57–61. sphatemic vitamin D-resistant rickets (report of a kindred with consanguinity). J 56. Rathore R, Nalawade TM, Pateel D, Mallikarjuna R. Oral manifestations of vitamin D Oral Pathol. 1973;2:203–14. resistant rickets in orthopantomogram. BMJ Case Rep. 2013;2013:bcr2012008318. 28. Cohen S, Becker GL. Origin, diagnosis, and treatment of the dental manifestations 57. Hillmann G, Geurtsen W. Pathohistology of undecalciﬁed primary teeth in vitamin of vitamin D-resistant rickets: review of the literature and report of case. J Am D-resistant rickets: review and report of two cases. Oral Surg Oral Med Oral Pathol Dent Assoc. 1976;92:120–9. Oral Radio Endod. 1996;82:218–24. 29. Ainley JE Jr. Manifestations of familial hypophosphatemia. J Endod. 1978;4:26–8. 58. Lyles KW, Burkes EJ Jr, McNamara CR, Harrelson JM, Pickett JP, Drezner MK. The 30. Rakocz M, Keating JR, Johnson R. Management of the primary dentition in vita- concurrence of hypoparathyroidism provides new insights to the pathophysiol- min D-resistant rickets. Oral Surg Oral Med Oral Pathol. 1982;54:166–71. ogy of X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 31. Chadwick BL, Aldred MJ. An unusual giant cell lesion in a child with vitamin 1985;60:711–7. D-resistant rickets. Int J Paediatr Dent. 1992;2:41–5. 59. Abe K, Ooshima T, Lily TS, Yasufuku Y, Sobue S. Structural deformities of decid- 32. Goodman JR, Gelbier MJ, Bennett JH, Winter GB. Dental problems associated with uous teeth in patients with hypophosphatemic vitamin D-resistant rickets. Oral hypophosphataemic vitamin D resistant rickets. Int J Paediatr Dent. 1998;8:19–28. Surg Oral Med Oral Pathol. 1988;65:191–8. 33. Pereira CM, de Andrade CR, Vargas PA, Coletta RD, de Almeida OP, Lopes MA. 60. Daley TD, Jarvis A, Wysocki GP, Kogon SL. X-ray microanalysis of teeth from Dental alterations associated with X-linked hypophosphatemic rickets. J Endod. healthy patients and patients with familial hypophosphatemia. Calcif Tissue Int. 2004;30:241–5. 1990;47:350–5. 34. Batra P, Tejani Z, Mars M. X-linked hypophosphatemia: dental and histologic 61. Nikiforuk G, Fraser D. Chemical determinants of enamel hypoplasia in children ﬁndings. J Can Dent Assoc. 2006;72:69–72. with disorders of calcium and phosphate homeostasis. J Dent Res. 35. Baroncelli GI, Angiolini M, Ninni E, Galli V, Saggese R, Giuca MR. Prevalence and 1979;58:1014–5. pathogenesis of dental and periodontal lesions in children with X-linked hypo- 62. Yuan L, Wu S, Xu H, Xiao J, Yang Z, Xia H, et al. Identiﬁcation of a novel PHEX phosphatemic rickets. Eur J Paediatr Dent. 2006;7:61–6. mutation in a Chinese family with X-linked hypophosphatemic rickets using 36. Douyere D, Joseph C, Gaucher C, Chaussain C, Courson F. Familial hypopho- exome sequencing. Biol Chem. 2015;396:27–33. sphatemic vitamin D-resistant rickets-prevention of spontaneous dental absces- 63. Resnick D. Implant placement and guided tissue regeneration in a patient with ses on primary teeth: a case report. Oral Surg Oral Med Oral Pathol Oral Radio congenital vitamin D-resistant rickets. J Oral Implantol. 1998;24:214–8. Endod. 2009;107:525–30. 64. Friberg B. Branemark system implants and rare disorders: a report of six cases. Int 37. Souza MA, Soares Junior LA, Santos MA, Vaisbich MH. Dental abnormalities and J Periodontics Restor Dent. 2013;33:139–48. oral health in patients with Hypophosphatemic rickets. Clin (Sao Paulo). 65. Shields ED, Scriver CR, Reade T, Fujiwara TM, Morgan K, Ciampi A, et al. X-linked 2010;65:1023–6. hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney. 38. Beltes C, Zachou E. Endodontic management in a patient with vitamin D-resistant Am. J. Hum. Genet. 1990;46:434–42. Rickets. J Endod. 2012;38:255–8. 66. Salmon B, Bardet C, Coyac BR, Baroukh B, Naji J, Rowe PS, et al. Abnormal 39. Rabbani A, Rahmani P, Ziaee V, Ghodoosi S. Dental problems in hypopho- osteopontin and matrix extracellular phosphoglycoprotein localization, and sphatemic rickets, a cross sectional study. Iran J Pediatr. 2012;22:531–4. odontoblast differentiation, in X-linked hypophosphatemic teeth. Connect Tissue 40. Cremonesi I, Nucci C, D’Alessandro G, Alkhamis N, Marchionni S, Piana G. X-linked Res. 2014;55:79–82. hypophosphatemic rickets: Enamel abnormalities and oral clinical ﬁndings. 67. Coyac BR, Falgayrac G, Baroukh B, Slimani L, Sadoine J, Penel G, et al. Tissue- Scanning. 2014;36:456–61. speciﬁc mineralization defects in the periodontium of the Hyp mouse model of 41. Ayesha Thabusum D, Stinton NM, Uston KA, Davis CD. Hypophosphatemic rickets X-linked hypophosphatemia. Bone. 2017;103:334–46. and pre-eruptive spontaneous dental abscess. Case Rep Dent. 2016;83:46–50. 68. Opsahl Vital S, Gaucher C, Bardet C, Rowe PS, George A, Linglart A, et al. Tooth 42. Paredes SEY, Segato RAB, Moreira LD, Moreira A, Serrano K, Rodrigues CT, et al. dentin defects reﬂect genetic disorders affecting bone mineralization. Bone. Dentoalveolar abscesses not associated with caries or trauma: A diagnostic 2012;50:989–97. hallmark of hypophosphatemic rickets initially misdiagnosed as hypochon- 69. Connor J, Olear EA, Insogna KL, Katz L, Baker S, Kaur R, et al. Conventional droplasia. Head Neck Pathol. 2017;12:604–9. Therapy in Adults With X-Linked Hypophosphatemia: Effects on enthesopathy 43. Murayama T, Iwatsubo R, Akiyama S, Amano A, Morisaki I. Familial hypopho- and dental disease. J Clin Endocrinol Metab. 2015;100:3625–32. sphatemic vitamin D-resistant rickets: dental ﬁndings and histologic study of 70. Wang X, Wang J, Liu Y, Yuan B, Ruest LB, Feng JQ, et al. The speciﬁc role of teeth. Oral Surg Oral Med Oral Pathol Oral Radio Endod. 2000;90:310–6. FAM20C in dentinogenesis. J Dent Res. 2015;94:330–6. 44. Soares EC, Costa FW, Ribeiro TR, Alves AP, Fonteles CS. Clinical approach in 71. Rangiani A, Cao ZG, Liu Y, Voisey Rodgers A, Jiang Y, Qin CL, et al. Dentin matrix familial hypophosphatemic rickets: report of three generations. Spec Care Dent. protein 1 and phosphate homeostasis are critical for postnatal pulp, dentin and 2013;33:304–7. enamel formation. Int J Oral Sci. 2012;4:189–95. 45. Andersen MG, Beck-Nielsen SS, Haubek D, Hintze H, Gjorup H, Poulsen S. Peria- 72. Boukpessi T, Hoac B, Coyac BR, Leger T, Garcia C, Wicart P, et al. Osteopontin and pical and endodontic status of permanent teeth in patients with hypopho- the dento-osseous pathobiology of X-linked hypophosphatemia. Bone. sphatemic rickets. J Oral Rehabil. 2012;39:144–50. 2017;95:151–61. 46. Al-Jundi SH, Hammad MM, Dabous I. Case report: hypophosphatemic rickets and 73. Coyac BR, Falgayrac G, Penel G, Schmitt A, Schinke T, Linglart A, et al. Impaired aggressive periodontitis: a review of the role of dentine matrix protein 1 in the mineral quality in dentin in X-linked hypophosphatemia. Connect Tissue Res. pathogenesis. Eur Arch Paediatr Dent. 2011;12:46–50. 2018;59:91–6. 47. Ye L, Liu R, White N, Alon US, Cobb CM. Periodontal status of patients with 74. Seow WK. Diagnosis and management of unusual dental abscesses in children. hypophosphatemic rickets: a case series. J Periodontol. 2011;82:1530–5. Aust Dent J. 2003;48:156–68. BDJ Open (2023) 9:2 X. Jin et al. 75. Hanisch M, Bohner L, Sabandal MMI, Kleinheinz J, Jung S. Oral symptoms and oral wouldbeusedfor research purposes andphotographs wouldbe publishedinthis health-related quality of life of individuals with x-linked hypophosphatemia. way. This study was approved by the Institutional Ethic Board of the Afﬁliated Head Face Med. 2019;15:8. Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China 76. Ye L, Zhang S, Ke H, Bonewald LF, Feng JQ. Periodontal breakdown in the Dmp1 (No. 2020-16). null mouse model of hypophosphatemic rickets. J Dent Res. 2008;87:624–9. 77. Zhang H, Chavez MB, Kolli TN, Tan MH, Fong H, Chu EY, et al. Dentoalveolar defects in the Hyp Mouse Model of X-linked Hypophosphatemia. Physiol Rep. ADDITIONAL INFORMATION 2020;99:419–28. Correspondence and requests for materials should be addressed to Baiping Fu. 78. Al-Jundi SH, Dabous IM, Al-Jamal GA. Craniofacial morphology in patients with hypophosphataemic vitamin-D-resistant rickets: A cephalometric study. J Oral Reprints and permission information is available at http://www.nature.com/ Rehabil. 2009;36:483–90. reprints Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims ACKNOWLEDGEMENTS in published maps and institutional afﬁliations. This work was supported by National Natural Science Foundation of China (81970982). XJ and YX contributed equally to this work and should be considered as co-ﬁrst authors. 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References

Hypophosphatemic Rickets

Bitzan, M; Goodyer, PR
Novel and de novo PHEX mutations in patients with hypophosphatemic rickets

Durmaz, E; Zou, M; Al-Rijjal, RA; Baitei, EY; Hammami, S; Bircan, I
Therapeutic management of hypophosphatemic rickets from infancy to adulthood

Linglart, A; Biosse-Duplan, M; Briot, K; Chaussain, C; Esterle, L; Guillaume-Czitrom, S
A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets

Francis, F; Hennig, S; Korn, B; Reinhardt, R; de Jong, P; Poustka, A
Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23

White, KE; Evans, WE; O'Riordan, JLH; Speer, MC; Econs, MJ; Lorenz-Depiereux, B
Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism

Feng, JQ; Ward, LM; Liu, S; Lu, Y; Xie, Y; Yuan, B
Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene

Levy-Litan, V; Hershkovitz, E; Avizov, L; Leventhal, N; Bercovich, D; Chalifa-Caspi, V
Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification

Rafaelsen, SH; Raeder, H; Fagerheim, AK; Knappskog, P; Carpenter, TO; Johansson, S
Familial hypophosphatemic rickets caused by a PHEX gene mutation accompanied by a NPR2 missense mutation

Zhao, Y; Yang, F; Wang, L; Che, H
Mutational analysis of the PHEX gene: novel point mutations and detection of large deletions by MLPA in patients with X-linked hypophosphatemic rickets

Clausmeyer, S; Hesse, V; Clemens, PC; Engelbach, M; Kreuzer, M; Becker-Rose, P
Defective Mineralization in X-Linked Hypophosphatemia Dental Pulp Cell Cultures

Coyac, BR; Hoac, B; Chafey, P; Falgayrac, G; Slimani, L; Rowe, PS
Extracellular matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, enzymes, and relationship to hypophosphatasia and X-linked hypophosphatemia

McKee, MD; Hoac, B; Addison, WN; Barros, NM; Millan, JL; Chaussain, C
Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets

Makitie, O; Doria, A; Kooh, SW; Cole, WG; Daneman, A; Sochett, E
Dentin structure in familial hypophosphatemic rickets: Benefits of vitamin D and phosphate treatment

Chaussain-Miller, C; Sinding, C; Septier, D; Wolikow, M; Goldberg, M; Garabedian, M
Diagnosis, treatment-monitoring and follow-up of children and adolescents with X-linked hypophosphatemia (XLH)

Rothenbuhler, A; Schnabel, D; Hogler, W; Linglart, A
X-linked hypophosphatemic rickets: an Italian experts’ opinion survey

Emma, F; Cappa, M; Antoniazzi, F; Bianchi, ML; Chiodini, I; Eller Vainicher, C
Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

Haffner, D; Emma, F; Eastwood, DM; Duplan, MB; Bacchetta, J; Schnabel, D
1,25-Dihydroxyvitamin D as Monotherapy for XLH: Back to the Future?

Ovejero, D; Gafni, RI; Collins, MT
X-linked hypophosphatemia: Molecular biology and treatment controversies

Thabet, MA; Truchina, O; Chan, JC
Long-term treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha-hydroxyvitamin D3

Rasmussen, H; Pechet, M; Anast, C; Mazur, A; Gertner, J; Broadus, A
Dental abnormalities in patients with familial hypophosphatemic vitamin D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D

Chaussain-Miller, C; Sinding, C; Wolikow, M; Lasfargues, JJ; Godeau, G; Garabedian, M
Prolonged high-dose phosphate treatment: a risk factor for tertiary hyperparathyroidism in X-linked hypophosphatemic rickets

Mäkitie, O; Kooh, S; Sochett, E
Nephrocalcinosis in X-linked hypophosphatemia: Effect of treatment versus disease

Taylor, A; Sherman, N; Norman, M
A randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis

Insogna, KL; Briot, K; Imel, EA; Kamenický, P; Ruppe, MD; Portale, AA
Dental manifestations of patient with vitamin D-resistant rickets

Souza, AP; Kobayashi, TY; Lourenco Neto, N; Silva, SM; Machado, MA; Oliveira, TM
Review of the dental implications of X-linked hypophosphataemic rickets (XLHR)

Sabandal, MM; Robotta, P; Burklein, S; Schafer, E
Electron optic analysis of human dentin in hypophosphatemic vitamin D-resistant rickets (report of a kindred with consanguinity)

Sauk, JJ; Witkop, CJ
Origin, diagnosis, and treatment of the dental manifestations of vitamin D-resistant rickets: review of the literature and report of case

Cohen, S; Becker, GL
Manifestations of familial hypophosphatemia

Ainley, JE
Management of the primary dentition in vitamin D-resistant rickets

Rakocz, M; Keating, JR; Johnson, R
An unusual giant cell lesion in a child with vitamin D-resistant rickets

Chadwick, BL; Aldred, MJ
Dental problems associated with hypophosphataemic vitamin D resistant rickets

Goodman, JR; Gelbier, MJ; Bennett, JH; Winter, GB
Dental alterations associated with X-linked hypophosphatemic rickets

Pereira, CM; de Andrade, CR; Vargas, PA; Coletta, RD; de Almeida, OP; Lopes, MA
X-linked hypophosphatemia: dental and histologic findings

Batra, P; Tejani, Z; Mars, M
Prevalence and pathogenesis of dental and periodontal lesions in children with X-linked hypophosphatemic rickets

Baroncelli, GI; Angiolini, M; Ninni, E; Galli, V; Saggese, R; Giuca, MR
Familial hypophosphatemic vitamin D-resistant rickets-prevention of spontaneous dental abscesses on primary teeth: a case report

Douyere, D; Joseph, C; Gaucher, C; Chaussain, C; Courson, F
Dental abnormalities and oral health in patients with Hypophosphatemic rickets

Souza, MA; Soares Junior, LA; Santos, MA; Vaisbich, MH
Endodontic management in a patient with vitamin D-resistant Rickets

Beltes, C; Zachou, E
Dental problems in hypophosphatemic rickets, a cross sectional study

Rabbani, A; Rahmani, P; Ziaee, V; Ghodoosi, S
X-linked hypophosphatemic rickets: Enamel abnormalities and oral clinical findings

Cremonesi, I; Nucci, C; D’Alessandro, G; Alkhamis, N; Marchionni, S; Piana, G
Hypophosphatemic rickets and pre-eruptive spontaneous dental abscess

Ayesha Thabusum, D; Stinton, NM; Uston, KA; Davis, CD
Dentoalveolar abscesses not associated with caries or trauma: A diagnostic hallmark of hypophosphatemic rickets initially misdiagnosed as hypochondroplasia

Paredes, SEY; Segato, RAB; Moreira, LD; Moreira, A; Serrano, K; Rodrigues, CT
Familial hypophosphatemic vitamin D-resistant rickets: dental findings and histologic study of teeth

Murayama, T; Iwatsubo, R; Akiyama, S; Amano, A; Morisaki, I
Clinical approach in familial hypophosphatemic rickets: report of three generations

Soares, EC; Costa, FW; Ribeiro, TR; Alves, AP; Fonteles, CS
Periapical and endodontic status of permanent teeth in patients with hypophosphatemic rickets

Andersen, MG; Beck-Nielsen, SS; Haubek, D; Hintze, H; Gjorup, H; Poulsen, S
Case report: hypophosphatemic rickets and aggressive periodontitis: a review of the role of dentine matrix protein 1 in the pathogenesis

Al-Jundi, SH; Hammad, MM; Dabous, I
Periodontal status of patients with hypophosphatemic rickets: a case series

Ye, L; Liu, R; White, N; Alon, US; Cobb, CM
Phosphate and Vitamin D Prevent Periodontitis in X-Linked Hypophosphatemia

Biosse Duplan, M; Coyac, BR; Bardet, C; Zadikian, C; Rothenbuhler, A; Kamenicky, P
Oral findings in patients with autosomal dominant hypophosphatemic bone disease and X-linked hypophosphatemia: further evidence that they are different diseases

Schwartz, S; Scriver, CR; Reade, TM; Shields, ED
Dental arch dimensions in children with hypophosphataemic Vitamin D resistant rickets

Al-Jundi, SH; Al-Naimy, YF; Alsweedan, S
Dental Development in Patients with Hypophosphatemia Rickets

Sh, AJ; Am, H
Dental hypersensitivity due to hypophosphataemia?

Hintze, H; Wenzel, A; Kruhoffer, F
Dental observations in vitamin D-resistant rickets with special reference to periapical lesions

Bender, IB; Naidorf, IJ
Familial vitamin D-refractory rickets

Gigliotti, R; Harrison, H; Reveley, RA; Drabkowski, AJ
Endodontic management of a patient with X-linked hypophosphataemic rickets

Alexander, S; Moloney, L; Kilpatrick, N
Oral manifestations of vitamin D resistant rickets in orthopantomogram

Rathore, R; Nalawade, TM; Pateel, D; Mallikarjuna, R
Pathohistology of undecalcified primary teeth in vitamin D-resistant rickets: review and report of two cases

Hillmann, G; Geurtsen, W
The concurrence of hypoparathyroidism provides new insights to the pathophysiology of X-linked hypophosphatemic rickets

Lyles, KW; Burkes, EJ; McNamara, CR; Harrelson, JM; Pickett, JP; Drezner, MK
Structural deformities of deciduous teeth in patients with hypophosphatemic vitamin D-resistant rickets

Abe, K; Ooshima, T; Lily, TS; Yasufuku, Y; Sobue, S
X-ray microanalysis of teeth from healthy patients and patients with familial hypophosphatemia

Daley, TD; Jarvis, A; Wysocki, GP; Kogon, SL
Chemical determinants of enamel hypoplasia in children with disorders of calcium and phosphate homeostasis

Nikiforuk, G; Fraser, D
Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Yuan, L; Wu, S; Xu, H; Xiao, J; Yang, Z; Xia, H
Implant placement and guided tissue regeneration in a patient with congenital vitamin D-resistant rickets

Resnick, D
Branemark system implants and rare disorders: a report of six cases

Friberg, B
X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney

Shields, ED; Scriver, CR; Reade, T; Fujiwara, TM; Morgan, K; Ciampi, A
Abnormal osteopontin and matrix extracellular phosphoglycoprotein localization, and odontoblast differentiation, in X-linked hypophosphatemic teeth

Salmon, B; Bardet, C; Coyac, BR; Baroukh, B; Naji, J; Rowe, PS
Tissue-specific mineralization defects in the periodontium of the Hyp mouse model of X-linked hypophosphatemia

Coyac, BR; Falgayrac, G; Baroukh, B; Slimani, L; Sadoine, J; Penel, G
Tooth dentin defects reflect genetic disorders affecting bone mineralization

Opsahl Vital, S; Gaucher, C; Bardet, C; Rowe, PS; George, A; Linglart, A
Conventional Therapy in Adults With X-Linked Hypophosphatemia: Effects on enthesopathy and dental disease

Connor, J; Olear, EA; Insogna, KL; Katz, L; Baker, S; Kaur, R
The specific role of FAM20C in dentinogenesis

Wang, X; Wang, J; Liu, Y; Yuan, B; Ruest, LB; Feng, JQ
Dentin matrix protein 1 and phosphate homeostasis are critical for postnatal pulp, dentin and enamel formation

Rangiani, A; Cao, ZG; Liu, Y; Voisey Rodgers, A; Jiang, Y; Qin, CL
Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia

Boukpessi, T; Hoac, B; Coyac, BR; Leger, T; Garcia, C; Wicart, P
Impaired mineral quality in dentin in X-linked hypophosphatemia

Coyac, BR; Falgayrac, G; Penel, G; Schmitt, A; Schinke, T; Linglart, A
Diagnosis and management of unusual dental abscesses in children

Seow, WK
Oral symptoms and oral health-related quality of life of individuals with x-linked hypophosphatemia

Hanisch, M; Bohner, L; Sabandal, MMI; Kleinheinz, J; Jung, S
Periodontal breakdown in the Dmp1 null mouse model of hypophosphatemic rickets

Ye, L; Zhang, S; Ke, H; Bonewald, LF; Feng, JQ
Dentoalveolar defects in the Hyp Mouse Model of X-linked Hypophosphatemia

Zhang, H; Chavez, MB; Kolli, TN; Tan, MH; Fong, H; Chu, EY
Craniofacial morphology in patients with hypophosphataemic vitamin-D-resistant rickets: A cephalometric study

Al-Jundi, SH; Dabous, IM; Al-Jamal, GA

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Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature

Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature

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Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature

Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature

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