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Review of the dental implications of X-linked hypophosphataemic rickets (XLHR)

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Abstract

Objectives

The aim of this article was to review the dental implications of X-linked hypophosphataemic rickets (XLHR) and to provide suggestions regarding the dental treatment of these patients.

Materials and methods

The following search items “x-linked hypophosphataemia, hypophosphataemic rickets, vitamin D-resistant rickets” were used for literature search. Only full-text articles were analysed and summarized to get an overview of the different treatments and outcomes of hypophosphataemic patients.

Results

Radiographically, very large pulp chambers with an abnormally high pulp volume/tooth volume ratio, suggesting taurodontism, are often evident. The affected teeth are characterised by a thin enamel layer and dentinal defects. The gender distribution of hypophosphataemic patients is almost equal, but postpubertary males seem to show a trend to develop more severe dental symptoms of the disease. Abscesses without any signs of dental caries or trauma are frequent findings. The most often affected teeth are incisors followed by molars and premolars.

Conclusions

Treatment options include frequent dental examination, application of topical fluoride varnish and sealing of pits and fissures to prevent microbial invasion that may result in pulpitis and further endodontic complications.

Clinical relevance

X-linked hypophosphataemic rickets is associated with marked structural alterations of dental hard tissues and the development of multiple abscesses and sinus tracts of dental origin. Therefore, profound knowledge of the various dental implications of XLHR is required to provide these patients with the best possible treatment options.

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References

  1. Beaton GH, Bengoa JM (1976) Nutrition in preventive medicine. World Health Organization Monograph Series No. 62 Chapter 6

  2. Uriu-Adams JY, Obican SG, Keen CL (2013) Vitamin D and maternal and child health: overview and implications for dietary requirements. Birth Defects Res C Embryo Today 99:24–44

    Article  PubMed  Google Scholar 

  3. Masuyama R (2014) Role of local vitamin D signalling and cellular calcium transport system in bone homeostasis. J Bone Miner Metab 32:1–9

    Article  PubMed  Google Scholar 

  4. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  PubMed  Google Scholar 

  5. Souza MA, Valente Soares LAV Jr, Alves dos Santos M, Vaisbich MH (2010) Dental abnormalities and oral health in patients with Hypophosphatemic rickets. Clinics 65:1023–1026

    Article  PubMed Central  PubMed  Google Scholar 

  6. Feng JQ, Clinkenbeard EL, Yuan B, White KE, Drezner MK (2013) Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia. Bone 54:213–221

    Article  PubMed Central  PubMed  Google Scholar 

  7. Bowden SA, Patel HP, Beebe A, McBride KL (2013) Successful medical therapy for hypophosphatemic rickets due to mitochondrial complex I deficiency induced de Toni-Debré-Fanconi Syndrome. Case Rep Pediatr 2013:354314

    PubMed Central  PubMed  Google Scholar 

  8. Root AW, Diamond FB (2002) Disorders of calcium metabolism in the child and adolescent. In: Sperling MA (ed) Pediatric endocrinology. Saunders, Philadelphia, p 646

    Google Scholar 

  9. Albright F, Butler AA, Bloomberg E (1937) Rickets resistant to vitamin D therapy. Am J Dis Child 54:529–547

    Google Scholar 

  10. Al-Jundi SH, Dabous IM, Al-Jamal GA (2009) Craniofacial morphology in patients with hypophosphataemic vitamin-D-resistant rickets: a cephalometric study. J Oral Rehabil 36:483–490

    Article  PubMed  Google Scholar 

  11. Reid IR, Hardy DC, Murphy WA, Teitelbaum SL, Bergfeld MA, Whyte MP (1989) X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults. Medicine (Baltimore) 68:336–352

    Article  Google Scholar 

  12. Petersen DJ, Boniface AM, Schranck FW, Rupich RC, Whyte MP (1992) X-linked hypophosphatemic rickets: a study (with literature review) of linear growth response to calcitriol and phosphate therapy. J Bone Miner Res 7:583–597

    Article  PubMed  Google Scholar 

  13. Holm IA, Nelson AE, Robinson BG, Mason RS, Marsh DJ, Cowell CT, Carpenter TO (2001) Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 86:3889–3899

    Article  PubMed  Google Scholar 

  14. Durmaz E, Zou M, Al-Rijjal RA, Baitei EY, Hammami S, Bircan İ, Akçurin S, Meyer B, Shi Y (2013) Novel and de novo PHEX mutations in patients with hypophosphatemic rickets. Bone 52:286–291

    Article  PubMed  Google Scholar 

  15. Carpenter TO (1997) New perspectives on the biology and treatment of X-linked hypophosphatemic rickets. Pediatr Clin N Am 44:443–466

    Article  Google Scholar 

  16. Souza AP, Kobayashi TY, LourenҫoNeto N, Silva SMB, Machado MAAM, Oliveira M (2013) Dental manifestations of patient with vitamin-D resistant rickets. J Appl Oral Sci 21:601–606

    PubMed Central  PubMed  Google Scholar 

  17. The HYP Consortium (1995) A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. Nat Genet 11:130–136

    Article  Google Scholar 

  18. Rowe PSN, Oudet CL, Francis F, Sinding C, Pannetier S, Econs MJ, Strom TM, Meitinger T, Garabedian M, David A, Macher MA, Questiaux E, Popowska E, Pronicka E, Read AP, Mokrzycki A, Glorieux FH, Drezner MK, Hanauer A, Lehrach H, Goulding JN, O’Riordan JLH (1997) Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP). Hum Mol Genet 6:539–549

    Article  PubMed  Google Scholar 

  19. Nesbitt T, Fujiwara I, Thomas R, Xiao ZS, Quarles LD, Drezner MK (1999) Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia. J Bone Miner Res 14:2027–2035

    Article  PubMed  Google Scholar 

  20. Kelly A, Levine MA (2010) Disorders of bone and mineral metabolism. In: Kappy MS, Allen DB, Mitchell EG (eds) Pediatric practice endocrinology. McGraw Hill, New York

    Google Scholar 

  21. Carpenter TO (2012) The expanding family of hypophosphatemic syndromes. J Bone Miner Metab 30:1–9

    Article  PubMed  Google Scholar 

  22. Rafaelsen SH, Ræder H, Fagerheim AK, Knappskog P, Carpenter TO, Johansson S, Bjerknes R (2013) Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23–related hypophosphatemia, dental anomalies, and ectopic calcification. J Bone Miner Res 28:1378–1385

    Article  PubMed  Google Scholar 

  23. Tenenhouse HS (1999) X-linked hypophosphataemia: a homologous disorder in humans and mice. Nephrol Dial Transplant 14:333–341

    Article  PubMed  Google Scholar 

  24. Brewer ED (2006) Panproximal tubular dysfunction (Fanconi Syndrome). In: McMilan JA, Feigin RD, DeAngelis C, Jones MD (eds) Oski’spediatrics, 4th edn. Lippincott & Wilkins, Philadelphia

    Google Scholar 

  25. Fadavi S, Rowold E (1990) Familial hypophosphatemic vitamin D-resistant rickets: review of the literature and report of case. ASDC J Dent Child 57:212–215

    PubMed  Google Scholar 

  26. Harris R, Sullivan HR (1960) Dental sequelae in deciduous dentition in vitamin D-resistant rickets, case report. Aust Dent J 5:200–203

    Article  Google Scholar 

  27. Bender IB, Naidorf IJ (1985) Dental observations in vitamin D-resistant rickets with special reference to periapical lesions. J Endod 11:514–520

    Article  PubMed  Google Scholar 

  28. Cohen S, Becker GL (1976) Origin, diagnosis, and treatment of the dental manifestations of vitamin D-resistant rickets: review of the literature and report of case. J Am Dent Assoc 92:120–129

    Article  PubMed  Google Scholar 

  29. Opsahl Vitala S, Gauchera C, Bardeta C, Rowed PS, Georgee A, Linglartf A, Chaussain C (2012) Tooth dentin defects reflect genetic disorders affecting bone mineralization. Bone 50:989–997

  30. Witkop CJ Jr (1971) Manifestations of genetic diseases in the human pulp. Oral Surg Oral Med Oral Pathol 32:278–316

    Article  PubMed  Google Scholar 

  31. Sauk JJ Jr, Witkop CJ Jr (1973) Electron optic analysis of human dentin in hypophosphatemic vitamin D-resistant rickets (report of a kindred with consanguinity). J Oral Pathol 2:203–214

    Article  PubMed  Google Scholar 

  32. Shellis RP (1983) Structural organization of calcospherites in normal and rachitic human dentine. Arch Oral Biol 28:85–95

    Article  PubMed  Google Scholar 

  33. Abe K, Ooshima T, Lily TS, Yasufuku Y, Sobue S (1988) Structural deformities of deciduous teeth in patients with hypophosphatemic vitamin D-resistant rickets. Oral Surg Oral Med Oral Pathol 65:191–198

    Article  PubMed  Google Scholar 

  34. Schwartz S, Scriver CR, Reade TM, Shields ED (1988) Oral findings in patients with autosomal dominant hypophosphatemic bone disease and X-linked hypophosphatemia: further evidence that they are different diseases. Oral Surg Oral Med Oral Pathol 66:310–314

    Article  PubMed  Google Scholar 

  35. Daley TD, Jarvis A, Wysocki GP, Kogon SL (1990) X-ray microanalysis of teeth from healthy patients and patients with familial hypophosphatemia. Calcif Tissue Int 47:350–355

    Article  PubMed  Google Scholar 

  36. Shields ED, Scriver CR, Reade T, Fujiwara TM, Morgan K, Ciampi A, Schwartz S (1990) X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney. Am J Hum Genet 46:434–442

    PubMed Central  PubMed  Google Scholar 

  37. Hillmann G, Geurtsen W (1996) Pathohistology of undecalcified primary teeth in vitamin D-resistant rickets: review and report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 82:218–224

    Article  PubMed  Google Scholar 

  38. Goodman JR, Gelbier MJ, Bennett JH, Winter GB (1998) Dental problems associated with hypophosphataemic vitamin D resistant rickets. Int J Paediatr Dent 8:19–28

    Article  PubMed  Google Scholar 

  39. Murayama T, Iwatsubo R, Akiyama S, Amano A, Morisaki I (2000) Familial hypophosphatemic vitamin D-resistant rickets: dental findings and histologic study of teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:310–316

    Article  PubMed  Google Scholar 

  40. Zambrano M, Nikitakis NG, Sanchez-Quevedo MC, Sauk JJ, Sedano H, Rivera H (2003) Oral and dental manifestations of vitamin D-dependent rickets type I: report of a pediatric case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95:705–709

    Article  PubMed  Google Scholar 

  41. Chaussain-Miller C, Sinding C, Wolikow M, Lasfargues J-J, Godeau G, Garabédian M (2003) Dental abnormalities in patients with familial hypophosphatemic vitamin D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D. J Pediatr 142:324–331

    Article  PubMed  Google Scholar 

  42. Seow WK (2003) Diagnosis and management of unusual dental abscesses in children. Aust Dent J 48:156–168

    Article  PubMed  Google Scholar 

  43. Batra P, Tejani Z, Mars M (2006) X-linked hypophosphatemia: dental and histologic findings. J Can Dent Assoc 72:69–72

    PubMed  Google Scholar 

  44. Chaussain-Miller C, Sinding C, Septier D, Wolikow M, Goldberg M, Garabedian M (2007) Dentin structure in familial hypophosphatemic rickets: benefits of vitamin D and phosphate treatment. Oral Dis 13:482–489

    Article  PubMed  Google Scholar 

  45. Douyere D, Joseph C, Gaucher C, Chaussain C, Courson F (2009) Familial hypophosphatemic vitamin D-resistant rickets-prevention of spontaneous dental abscesses on primary teeth: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107:525–530

    Article  PubMed  Google Scholar 

  46. Rabbani A, Rahmani P, Ziaee V, Ghodoosi S (2012) Dental problems in hypophosphatemic rickets, a cross sectional study. Iran J Pediatr 22:531–534

    PubMed Central  PubMed  Google Scholar 

  47. Andersen MG, Beck-Nielsen SS, Haubek D, Hintze H, Gjørup H, Poulsen S (2012) Periapical and endodontic status of permanent teeth in patients with hypophosphatemic rickets. J Oral Rehabil 39:144–150

    Article  PubMed  Google Scholar 

  48. Rathore R, Nalawade TM, Pateel D, Mallikarjuna R (2013) Oral manifestations of vitamin D resistant rickets in orthopantomogram. BMJ Case Rep. doi:10.1136/bcr-2012-008318

    PubMed Central  PubMed  Google Scholar 

  49. Studart Soares EC, Gurgel Costa FW, Rodrigues Ribeiro T, NegreirosNunes Alves AP, SáRorizFonteles C (2013) Clinical approach in familial hypophosphatemic rickets: report of three generations. Spec Care Dentist 33:304–307

  50. Larmas M, Hietala EL, Simila S, Pajari U (1991) Oral manifestations of familial hypophosphatemic rickets after phosphate supplement therapy: a review of the literature and report of case. ASDC J Dent Child 58:328–334

    PubMed  Google Scholar 

  51. Seow WK, Needleman HL, Holm IA (1995) Effect of familial hypophosphatemic rickets on dental development: a controlled, longitudinal study. Pediatr Dent 17:346–350

    PubMed  Google Scholar 

  52. Salmon B, Bardet C, Khaddam M, Naji J, Coyac BR, Baroukh B, Letourneur F, Lesieur J, Decup F, Le Denmat D, Nicoletti A, Poliard A, Rowe PS, Huet E, Opsahl Vital S, Linglart A, McKee MD, Chaussain C (2013) MEPE-derived ASARM peptide inhibits odontogenic differentiation of dental pulp stem cells and impairs mineralization in tooth models of X-linked hypophosphatemia. PLoS One 8:e56749

    Article  PubMed Central  PubMed  Google Scholar 

  53. Seeto E, Seow WK (1991) Scanning electron microscopic analysis of dentin in vitamin D-resistant rickets–assessment of mineralization and correlation with clinical findings. Pediatr Dent 13:43–48

    PubMed  Google Scholar 

  54. Goldberg M, Septier D, Bourd K, Hall R, Jeanny JC, Jonet L, Colin S, Tager F, Chaussain-Miller C, Garabédian M, George A, Goldberg H, Menashi S (2002) The dentino-enamel junction revisited. Connect Tissue Res 43:482–489

    Article  PubMed  Google Scholar 

  55. Via WF Jr (1967) “Spontaneous” degeneration of the dental pulp associated with phosphate diabetes. Oral Surg Oral Med Oral Pathol 24:623–628

    Article  PubMed  Google Scholar 

  56. Pliskin ME, Brown AM, Baden EE, Kimball HG (1975) Vitamin D resistant rickets of a young adult patient. A review and case report. J Oral Med 30:77–80

    PubMed  Google Scholar 

  57. McWhorter AG, Seale NS (1991) Prevalence of dental abscess in a population of children with vitamin D-resistant rickets. Pediatr Dent 13:91–96

    PubMed  Google Scholar 

  58. Cehreli ZC, Turgut M, Olmez S, Dagdeviren A, Atilla P (2000) Short term human primary pulpal response after direct pulp capping with fourth-generation dentin adhesives. J Clin Pediatr Dent 25:65–71

    PubMed  Google Scholar 

  59. Fusayama T, Nakamura M, Kurosaki N, Iwaku M (1979) Non-pressure adhesion of a new adhesive restorative resin. J Dent Res 58:1364–1370

    Article  PubMed  Google Scholar 

  60. Liu S, Gupta A, Quarles LD (2007) Emerging role of fibroblast growth factor 23 in a bone–kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization. Curr Opin Nephrol Hypertens 16:329–335

  61. Seow WK, Romaniuk K, Sclavos S (1989) Micromorphologic features of dentin in vitamin D-resistant rickets: correlation with clinical grading of severity. Pediatr Dent 11:203–208

    PubMed  Google Scholar 

  62. Seow WK, Latham SC (1986) The spectrum of dental manifestations in vitamin D-resistant rickets: implications for management. Pediatr Dent 8:245–250

    PubMed  Google Scholar 

  63. Rakocz M, Keating J III, Johnson R (1982) Management of the primary dentition in vitamin D-resistant rickets. Oral Surg Oral Med Oral Pathol 54:166–171

    Article  PubMed  Google Scholar 

  64. Shroff DV, McWhorter AG, Seale NS (2002) Evaluation of aggressive pulp therapy in a population of vitamin D-resistant rickets patients: a follow-up of 4 cases. Pediatr Dent 24:347–349

    PubMed  Google Scholar 

  65. Mireku AS, Romberg E, Fuoad AF, Arola D (2010) Vertical fracture of root filled teeth restored with posts: the effects of patient age and dentine thickness. Int Endod J 43:218–225

    Article  PubMed Central  PubMed  Google Scholar 

  66. Foster BL, Ramnitz MS, Gafni RI, Burke AB, Boyce AM, Lee JS, Wright JT, Akintoye SO, Somerman MJ, Collins MT (2014) Rare bone diseases and their dental, oral, and craniofacial manifestations. J Dent Res 93:7S–19S

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Sabandal, M.M.I., Robotta, P., Bürklein, S. et al. Review of the dental implications of X-linked hypophosphataemic rickets (XLHR). Clin Oral Invest 19, 759–768 (2015). https://doi.org/10.1007/s00784-015-1425-4

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