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Cited by 7Alkaline Phosphatase Research Studiesdental development and anomaliesBone and Dental Protein Studies

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The impact of enzyme replacement therapy on the oral health manifestations of hypophosphatasia among children: a scoping review

Smart, G., Jensen, E. D., Poirier, B. F., Sethi, S.·2023·European Archives of Paediatric Dentistry
DOI 10.1007/s40368-023-00796-0
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Abstract

Purpose A scoping review to describe the use of enzyme replacement therapy (ERT) in the form of asfotase alfa to decrease the severity of oral manifestations in children with hypophosphatasia (HPP). Methods Six databases were searched using keywords and index terms related to "hypophosphatasia," "children," and "enzyme replacement therapy." Duplicates were removed and two independent reviewers screened the titles and abstracts to identify articles for full-text review. Extracted data was summarised narratively. Results The systematic search identified 3548 articles, with 171 suitable for full-text review and a final 22 that met inclusion criteria. Enzyme replacement therapy generally resulted in a reduction in the presence and severity of oral manifestations of HPP. However, numerous studies failed to report specific details regarding the nature of oral health outcomes and there were reported cases of further loss of primary teeth. Conclusions The available evidence suggests that that ERT in the form of asfotase alfa for HPP in infants and young children leads to improved oral health outcomes. It is recommended that the outcomes are improved with earlier initiation of ERT. Further, well-designed clinical research is required to assess oral health improvements and decreased morbidity associated with the early loss of teeth.

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References 52 · Cited by 7

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  1. Anbarserri NM, Ismail KM, Anbarserri H, Alanazi D, AlSaffan AD, Baseer MA, Shaheen R. Impact of severity of tooth loss on oral-health-related quality of life among dental patients. J Fam Med Prim Care. 2020;9(1):187. · DOI
  2. Arksey H, O’Malley L. Scoping studies: towards a methodological framework. Int J Soc Res Methodol. 2005;8(1):19–32. · DOI · Paper page
  3. Bowden SA, Foster BL. Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy. Drug Des Dev Ther. 2018;12:3147. · DOI
  4. Faser D. Hypophosphatasie. Am J Med. 1957;22:730–46. · DOI
  5. Feeney C, Stanford N, Lee S, Barry S. Hypophosphatasia and the importance of the general dental practitioner–a case series and discussion of upcoming treatments. Br Dent J. 2018;224(12):937–43. · DOI
  6. Foster B, Kuss P, Yadav M, Kolli T, Narisawa S, Lukashova L, Cory E, Sah R, Somerman M, Millán J. Conditional Alpl ablation phenocopies dental defects of hypophosphatasia. J Dent Res. 2017;96(1):81–91. · DOI
  7. Gerritsen AE, Allen PF, Witter DJ, Bronkhorst EM, Creugers NH. Tooth loss and oral health-related quality of life: a systematic review and meta-analysis. Health Qual Life Outcomes. 2010;8(1):1–11. · DOI
  8. Hofmann C, Girschick H, Mentrup B, Graser S, Seefried L, Liese J, Jakob F. Clinical aspects of hypophosphatasia: an update. Clin Rev Bone Miner Metab. 2013;11(2):60–70. · DOI
  9. Hofmann CE, Harmatz P, Vockley J, Högler W, Nakayama H, Bishop N, Martos-Moreno GA, Moseley S, Fujita KP, Liese J. Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study. J Clin Endocrinol Metab. 2019;104(7):2735–47. · DOI
  10. Khan A, Josse R, Kannu P, Villeneuve J, Paul T, Van Uum S, Greenberg C. Hypophosphatasia: Canadian update on diagnosis and management. Osteoporos Int. 2019;30(9):1713–22. · DOI
  11. Kiselnikova L, Vislobokova E, Voinova V. Dental manifestations of hypophosphatasia in children and the effects of enzyme replacement therapy on dental status: a series of clinical cases. Clin Case Rep. 2020;8(5):911–8. · DOI
  12. Kishnani PS, Rockman-Greenberg C, Denker AE, Moseley S, Whyte MP. Biochemical and physical function outcomes after 5 years of treatment with asfotase alfa in adolescents and adults with hypophosphatasia: phase 2 study results. Bone Abstr. 2017. https://doi.org/10.1530/boneabs.6.OC25. · DOI
  13. Kosnik-Infinger L, Gendron C, Gordon CB, Pan BS, van Aalst JA, Vogel TW. Enzyme replacement therapy for congenital hypophosphatasia allows for surgical treatment of related complex craniosynostosis: a case series. Neurosurg Focus. 2015;38(5):E10. · DOI
  14. Levac D, Colquhoun H, O’Brien KK. Scoping studies: advancing the methodology. Implement Sci. 2010;5(1):69. · DOI · Paper page
  15. Liu M, Liu M, Liang X, Wu D, Li W, Su C, Cao B, Chen J, Gong C. Clinical and genetic characteristics of hypophosphatasia in Chinese children. Orphanet J Rare Dis. 2021;16(1):1–13. · DOI
  16. Mikelis F, Koletsi D. Scoping reviews in orthodontics: are they justified? Prog Orthod. 2022;23(1):48. · DOI
  17. Millán JL, Plotkin H. Hypophosphatasia-pathophysiology and treatment. Actual Osteol. 2012;8(3):164.
  18. Millán JL, Whyte MP. Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int. 2016;98(4):398–416. · DOI
  19. Mori M, DeArmey SL, Weber TJ, Kishnani PS. Case series: odontohypophosphatasia or missed diagnosis of childhood/adult-onset hypophosphatasia?–Call for a long-term follow-up of premature loss of primary teeth. Bone Rep. 2016;5:228–32. · DOI
  20. Mornet E. Molecular genetics of hypophosphatasia and phenotype-genotype correlations. In: Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP). Dordrecht: Springer; 2015. p. 25–43. · DOI
  21. Nadelman P, Magno MB, Pithon MM, de Castro ACR, Maia LC. Does the premature loss of primary anterior teeth cause morphological, functional and psychosocial consequences? Braz Oral Res. 2021. https://doi.org/10.1590/1807-3107bor-2021.vol35.0092. · DOI
  22. Okawa R, Nakano K, Matsumoto M, Kawabata K, Ooshima T. Oral manifestations of patients with hypophosphatasia. Pediatr Dent J. 2012;22(2):155–62. · DOI
  23. Okawa R, Kokomoto K, Yamamura-Miyazaki N, Michigami T, Nakano K. Oral findings in patient with lethal hypophosphatasia treated with enzyme replacement therapy. Pediatr Dent J. 2017;27(3):153–6. · DOI
  24. Okawa R, Miura J, Kokomoto K, Nakano K. Evaluation of avulsed primary incisor in 3-year-old girl with hypophosphatasia who received enzyme replacement therapy. Pediatr Dent J. 2018;28(3):136–40. · DOI
  25. Okawa R, Kokomoto K, Kitaoka T, Kubota T, Watanabe A, Taketani T, Michigami T, Ozono K, Nakano K. Japanese nationwide survey of hypophosphatasia reveals prominent differences in genetic and dental findings between odonto and non-odonto types. PLoS ONE. 2019;14(10): e0222931. · DOI
  26. Okawa R, Matayoshi S, Kariya R, Ogaya Y, Nomura R, Nakano K. Effects of enzyme replacement therapy for primary teeth in a patient with infantile hypophosphatasia. J Clin Pediatr Dent. 2020;44(5):348–51. · DOI
  27. Okawa R, Kokomoto K, Nakano K. Dental effects of enzyme replacement therapy in case of childhood-type hypophosphatasia. BMC Oral Health. 2021;21(1):1–8. · DOI
  28. Padidela R. Asfotase alfa treatment in perinatal and infantile hypophosphatasia: safe and sustained efficacy. Lancet Diabetes Endocrinol. 2019;7(2):76–8. · DOI
  29. Pimstone B, Eisenberg E, Silverman S. Hypophosphatasia: genetic and dental studies. Ann Intern Med. 1966;65(4):722–9. · DOI
  30. Reibel A, Manière MC, Clauss F, Droz D, Alembik Y, Mornet E, Bloch-Zupan A. Orodental phenotype and genotype findings in all subtypes of hypophosphatasia. Orphanet J Rare Dis. 2009;4(1):1–10. · DOI
  31. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev: PER. 2013;10:380–8.
  32. Rodrigues T, Georgetti AP, Martins L, Pereira Neto JS, Foster BL, Nociti FH Jr. Clinical correlate: case study of identical twins with cementum and periodontal defects resulting from odontohypophosphatasia. In: Mineralized tissues in oral and craniofacial science: biological principles and clinical correlates. Ames: Wiley-Blackwell; 2012. p. 183–90. · DOI
  33. Schroth RJ, Long C, Lee VH, Alai-Towfigh H, Rockman-Greenberg C. Dental outcomes for children receiving asfotase alfa for hypophosphatasia. Bone. 2021;152: 116089. · DOI · Paper page
  34. Strandbech OS, Lund A, Ostergaard E. Excellent response to asfotase alfa treatment in an adolescent patient with hypophosphatasia. JIMD Reports. 2021;59(1):10–5. · DOI
  35. Takagi M, Kato S, Muto T, Sano Y, Akiyama T, Takagi J, Okumura A, Iwayama H. Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report. Clin Pediatr Endocrinol. 2020;29(3):115–8. · DOI
  36. Wang Z, Zhang K, Zheng G, Qiao W, Su Y. Current concepts in odontohypophosphatasia form of hypophosphatasia and report of two cases. BMC Oral Health. 2016;16(1):1–8. · DOI
  37. Whyte MP. Hypophosphatasia: enzyme replacement therapy brings new opportunities and new challenges. J Bone Miner Res. 2017;32(4):667–75. · DOI
  38. Whyte MP, Teitelbaum SL, Murphy WA, Bergfeld MA, Avioli LV. Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature. Medicine. 1979;58(5):329–47. · DOI
  39. Whyte MP, Valdes R Jr, Ryan LM, McAlister WH. Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease. J Pediatr. 1982;101(3):379–86. · DOI
  40. Whyte MP, Mahuren J, Fedde K, Cole F, McCabe E, Coburn S. Perinatal hypophosphatasia: tissue levels of vitamin B6 are unremarkable despite markedly increased circulating concentrations of pyridoxal-5’-phosphate. Evidence for an ectoenzyme role for tissue-nonspecific alkaline phosphatase. J Clin Invest. 1988;81(4):1234–9. · DOI
  41. Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;366(10):904–13. · DOI
  42. Whyte MP, Leelawattana R, Reinus WR, Yang C, Mumm S, Novack DV. Acute severe hypercalcemia after traumatic fractures and immobilization in hypophosphatasia complicated by chronic renal failure. J Clin Endocrinol Metab. 2013;98(12):4606–12. · DOI
  43. Whyte MP, Simmons JH, Moseley S, Fujita KP, Bishop N, Salman NJ, Taylor J, Phillips D, McGinn M, McAlister WH. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. Lancet Diabetes Endocrinol. 2019;7(2):93–105. · DOI
  44. Zauza D, Dotto L, Moher D, Tricco AC, Agostini B, Sarkis-Onofre R. There is room for improvement in the use of scoping reviews in dentistry. J Dent. 2022;122:104161. · DOI · Paper page

Metadata

Authors
Smart, G., Jensen, E. D., Poirier, B. F., & Sethi, S.
Affiliations
  • Women's and Children's Hospital (AU)
  • The University of Adelaide (AU)
Corresponding author
Smart, G.
ORCID
Venue
European Archives of Paediatric Dentistry
Publisher
Springer Science and Business Media LLC
Published
2023-04-10
Volume
24
Issue
4
Pages
429-440
ISSN
  • 1818-6300 (ISSN-L)
  • 1996-9805
DOI
10.1007/s40368-023-00796-0
OpenAlex
W4363646465
Cited by
7
References
52
Citations by year
2026: 2 · 2025: 3 · 2024: 2
FWCI
0.25
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • European Archives of Paediatric Dentistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
  • Health Sciences › Dentistry › General Dentistry › dental development and anomalies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
Keywords
hypophosphatasia, asfotase alfa, enzyme replacement therapy, oral manifestations, children, primary tooth loss, early treatment initiation, oral health outcomes
MeSH terms
Child, Child, Preschool, Humans, Hypophosphatasia, Infant, Oral Health, Enzyme Replacement Therapy

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Smart, G., Jensen, E. D., Poirier, B. F., & Sethi, S. (2023). The impact of enzyme replacement therapy on the oral health manifestations of hypophosphatasia among children: a scoping review. European Archives of Paediatric Dentistry. https://doi.org/10.1007/s40368-023-00796-0