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The devastating consequences of hypophosphatasia (HPP) are progressive and can worsen in adulthood.1-4

Manifestations of hypophosphatasia in adults can include

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  • Skeletal
  • Muscular/Rheumatologic
  • Physical function
  • Dental
  • Renal
Loss of physical function impacting activities of daily living15
Unusual gait15
Impaired mobility (including the need for assistive devices such as wheelchair, walker, crutches, or cane)1,15
Alkaline phosphatase (ALP) is necessary for ongoing skeletal health because of the body’s constant bone mass turnover.1,5,21,22

Skeletal manifestations of hypophosphatasia can result in a high burden of disease in adults.1

55 years of age23,a
56 years24 of age18,a
Bilateral acute subtrochanteric femoral fractures
Recurrent, poorly healing metatarsal stress fracture
32 years of age25,a
55 years of age26,a
Pseudofracture of the distal fibula
Multiple vertebral crush fractures
Adults with hypophosphatasia experience a large number of fractures (mean [standard deviation, SD] of 12.9 [19.0] fractures [range, 1-100]).15,b

Pain and impaired mobility severely limit activities of daily living in adults with hypophosphatasia.15

Severe, chronic pain and significant disability can have a dramatic impact on quality of life in adults with hypophosphatasia.2,3,27,28

Adults with hypophosphatasia live with significant physical function and mobility impairments.3,15

A majority of adults with hypophosphatasia reported difficulty with activities of daily living.15,d

Difficulties with activities of daily living can severely impact quality of life.3

Adults with hypophosphatasia can be significantly disabled.3

View case studies to learn about disease progression in adults with hypophosphatasia.

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aRadiographs are from different patients with hypophosphatasia.

bCombined data from HIPS/HOST, an Internet questionnaire and telephone survey that queried demographics, hypophosphatasia-related illness history, disease progression, and health-related quality of life. One hundred twenty-five adults participated.15

cData from HIPS, an Internet questionnaire that queried demographics, HPP-related illness history, disease progression, and health-related quality of life. Eighty-nine adults participated.15

dHOST was a telephone survey that queried demographics, HPP-related illness history, disease progression, and health-related quality of life. Thirty-six adults participated.15

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References:
  1. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388.
  2. Whyte MP, Leung E, Wilcox W, et al; for Study 011-10 Investigators. Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms. Poster presented at: 2014 Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting; May 3-6, 2014; Vancouver, BC.
  3. Weber TJ, Sawyer EK, Moseley S, Odrljin T, Kishnani PS. Burden of disease in adult patients with hypophosphatasia: results from patient-reported outcome surveys. Poster presented at: Endocrine Society Annual Meeting; March 5-8, 2015; San Diego, CA.
  4. Weber TJ, Sawyer EK, Moseley S, Odrljin T, Kishnani PS. Fracture and surgical burden in pediatric and adult patients with hypophosphatasia: results from patient-reported outcome surveys [IOF abstract P146]. Osteoporos Int. 2015;26(suppl 1):C89.
  5. Beck C, Morbach H, Stenzel M, Collmann H, Schneider P, Girschick HJ. Hypophosphatasia—recent advances in diagnosis and treatment. Open Bone J. 2009;1:8-15.
  6. Coe JD, Murphy WA, Whyte MP. Management of femoral fractures and pseudofractures in adult hypophosphatasia. J Bone Joint Surg Am. 1986;68(7):981-990.
  7. Gagnon C, Sims NA, Mumm S, et al. Lack of sustained response to teriparatide in a patient with adult hypophosphatasia. J Clin Endocrinol Metab. 2010;95(3):1007-1012.
  8. Schalin-Jäntti C, Mornet E, Lamminen A, Välimäki MJ. Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia. J Clin Endocrinol Metab. 2010;95(12):5174-5179.
  9. Silva I, Castelão W, Mateus M, Branco JC. Childhood hypophosphatasia with myopathy: clinical report with recent update. Acta Rheumatol Port. 2012;37(1):92-96.
  10. Whyte MP. Hypophosphatasia. In: Thakker RV, Whyte MP, Eisman JA, Igarashi T, eds. Genetics of Bone Biology and Skeletal Disease. London, UK: Academic Press; 2013:337-360.
  11. Whyte MP, Murphy WA, Fallon MD. Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred. Am J Med. 1982;72(4):631-641.
  12. Weinstein RS, Whyte MP. Heterogeneity of adult hypophosphatasia. Report of severe and mild cases. Arch Intern Med. 1981;141(6):727-731.
  13. Beck C, Morbach H, Wirth C, Beer M, Girschick HJ. Whole-body MRI in the childhood form of hypophosphatasia. Rheumatol Int. 2011;31(10):1315-1320.
  14. Braunstein NA. Multiple fractures, pain, and severe disability in a patient with adult-onset hypophosphatasia. Bone Rep. 2016;4:1-4.
  15. Data on file, Alexion Pharmaceuticals.
  16. Chuck AJ, Pattrick MG, Hamilton E, Wilson R, Doherty M. Crystal deposition in hypophosphatasia: a reappraisal. Ann Rheum Dis. 1989;48(7):571-576.
  17. Whyte MP. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci. 2010;1192:190-200.
  18. Whyte MP. Hypophosphatasia: nature’s window on alkaline phosphatase function in humans. In: Bilezikian JP, Raisz LG, Martin TJ, ed. Principles of Bone Biology. Vol 2. 3rd ed. San Diego, CA: Academic Press; 2008:1573-1598.
  19. Suvarna GS, Nadiger RK, Guttal SS, Shetty O. Prosthetic rehabilitation of hypophosphatasia with precision attachment retained unconventional partial denture: a case report. J Clin Diagn Res. 2014;8(12):ZD08-ZD10.
  20. Eade AWT, Swannell AJ, Williamson N. Pyrophosphate arthropathy in hypophosphatasia. Ann Rheum Dis. 1981;40(2):164-170.
  21. Kini U, Nandeesh BN. Physiology of bone formation, remodeling, and metabolism. In: Fogelman I, Gnanasegaran G, van der Wall H, eds. Radionuclide and Hybrid Bone Imaging. Berlin, Germany: Springer-Verlag Berlin Heidelberg; 2012:29-57.
  22. Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008;3(suppl 3):S131-S139.
  23. Sutton RAL, Mumm S, Coburn SP, Ericson KL, Whyte MP. "Atypical femoral fractures" during bisphosphonate exposure in adult hypophosphatasia. J Bone Miner Res. 2012;27(5):987-994.
  24. Whyte MP, Mumm S, Deal C. Adult hypophosphatasia treated with teriparatide. J Clin Endocrinol Metab. 2007;92(4):1203-1208.
  25. Barvencik F, Beil FT, Gebauer M, et al. Skeletal mineralization defects in adult hypophosphatasia--a clinical and histological analysis. Osteoporos Int. 2011;22(10):2667-2675.
  26. Cundy T, Michigami T, Tachikawa K, et al. Reversible deterioration in hypophosphatasia caused by renal failure with bisphosphonate treatment. J Bone Miner Res. 2015;30(9):1726-1737.
  27. Whyte MP, Madson KL, Munns CF, et al. A retrospective, multi-national, non-interventional, natural history study of the childhood form of hypophosphatasia [abstract LB-OR01]. Endocrine Society's 97th Annual Meeting and Expo website. https://endo.confex.com/endo/2015endo/webprogram/Paper22822.html. Accessed October 26, 2017.
  28. Donaldson LJ, Reckless IP, Scholes S, Mindell JS, Shelton NJ. The epidemiology of fractures in England. J Epidemiol Community Health. 2008;62(2):174-180.