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

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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

  • 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.

    Article  Google Scholar 

  • Arksey H, O’Malley L. Scoping studies: towards a methodological framework. Int J Soc Res Methodol. 2005;8(1):19–32.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • European Union Clinical Trials Register. A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Concurrent Control Study of the Safety, Efficacy, and Pharmacokinetics of ENB-0040 (Human Recombinant Tissue-Nonspecific Alkaline Phosphatase Fusion Protein) in Adolescents and Adults with Hypophosphatasia (HPP). EU Clinical Trials Register. 2018.

  • Faser D. Hypophosphatasie. Am J Med. 1957;22:730–46.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Foster ED, Deardorff A. Open Science Framework (OSF). J Med Libr Assoc: JMLA. 2017;105(2):203–6.

    Article  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Levac D, Colquhoun H, O’Brien KK. Scoping studies: advancing the methodology. Implement Sci. 2010;5(1):69.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Mikelis F, Koletsi D. Scoping reviews in orthodontics: are they justified? Prog Orthod. 2022;23(1):48.

    Article  PubMed  PubMed Central  Google Scholar 

  • Millán JL, Plotkin H. Hypophosphatasia-pathophysiology and treatment. Actual Osteol. 2012;8(3):164.

    PubMed  PubMed Central  Google Scholar 

  • Millán JL, Whyte MP. Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int. 2016;98(4):398–416.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mornet E. Molecular genetics of hypophosphatasia and phenotype-genotype correlations. In: Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP). Dordrecht: Springer; 2015. p. 25–43.

    Chapter  Google Scholar 

  • Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol. 2018a;18(1):143.

    Article  PubMed  PubMed Central  Google Scholar 

  • Munn Z, Stern C, Aromataris E, Lockwood C, Jordan Z. What kind of systematic review should I conduct? A proposed typology and guidance for systematic reviewers in the medical and health sciences. BMC Med Res Methodol. 2018b;18(1):5.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Okawa R, Nakano K, Matsumoto M, Kawabata K, Ooshima T. Oral manifestations of patients with hypophosphatasia. Pediatr Dent J. 2012;22(2):155–62.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Padidela R. Asfotase alfa treatment in perinatal and infantile hypophosphatasia: safe and sustained efficacy. Lancet Diabetes Endocrinol. 2019;7(2):76–8.

    Article  PubMed  Google Scholar 

  • Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10(1):1–11.

    Article  Google Scholar 

  • Peters MDJ, Godfrey C, McInerney P, Munn Z, Tricco AC and Khalil H. Chapter 11: Scoping Reviews (2020 version). JBI Manual for Evidence Synthesis. Aromataris E and M. Z. Adelaide, JBI, 2020.

  • Pimstone B, Eisenberg E, Silverman S. Hypophosphatasia: genetic and dental studies. Ann Intern Med. 1966;65(4):722–9.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev: PER. 2013;10:380–8.

    PubMed  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • United States National Library of Medicine ClinicalTrials.gov. Study of Asfotase Alfa in Children With Hypophosphatasia (HPP). U.S. National Library of Medicine ClinicalTrials.gov. 2019.

  • 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.

    Article  Google Scholar 

  • Whyte MP. Hypophosphatasia: enzyme replacement therapy brings new opportunities and new challenges. J Bone Miner Res. 2017;32(4):667–75.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatric Dentistry, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA, 5006, Australia

    G. Smart & E. D. Jensen

  2. Adelaide Dental School, The University of Adelaide, Adelaide, SA, Australia

    E. D. Jensen, B. F. Poirier & S. Sethi

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Smart, G., Jensen, E.D., Poirier, B.F. et al. The impact of enzyme replacement therapy on the oral health manifestations of hypophosphatasia among children: a scoping review. Eur Arch Paediatr Dent 24, 429–440 (2023). https://doi.org/10.1007/s40368-023-00796-0

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