eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Hypophosphatasia: Treatment & Medication

Author: Horacio Plotkin, MD, FAAP, Adjunct Associate Professor of Pediatrics and Orthopedic Surgery, University of Nebraska School of Medicine
Coauthor(s): George A Anadiotis, DO, Consulting Staff, Division of Clinical and Biochemical Genetics, Department of Pediatric Rehabilitation and Development, Emmanuel Children's Hospital
Contributor Information and Disclosures

Updated: May 2, 2008

Treatment

Medical Care

Currently, no medical therapy is available. Various treatments have been attempted, including zinc, magnesium, cortisone, plasma, and enzyme replacement therapy. The results have been inconsistent.

Enzyme replacement from birth in TNALP knockout mice using bone-targeted, recombinant human TNALP prevented the disease.4

One report of an adult female patient treated with teriparatide documented fracture repair that accompanied correction of hypophosphatasemia and hyperphosphatemia and bone marker responses that indicated enhanced skeletal remodeling.5 Literature reports also suggest that donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment to form TNSALP-replete osteoblasts, which may improve mineralization.6

The effects of bone marrow transplant in hypophosphatasia are transient, and bone lesions may recur approximately 6 months after the transplant. Nonsteroidal anti-inflammatory drugs have been used in patients with childhood hypophosphatasia with some clinical improvement, although more experience is warranted before this therapy can be recommended. Enzyme replacement therapy with partially purified plasma enzyme was attempted, but with little clinical improvement. Some success has been achieved in delivering functional TNSALP enzyme to bone.

Supportive care is necessary to decrease the morbidity associated with hypophosphatasia. Regularly examine infants and children to check for evidence of increased intracranial pressure. Observe fractures closely. Adult pseudofractures may require orthopedic care to heal properly. A dentist should closely monitor all individuals with hypophosphatasia.

Surgical Care

Orthopedic surgical involvement may be necessary in patients with hypophosphatasia. Rachitic deformities and gait abnormalities require orthopedic evaluation. For them to heal completely, pseudofractures of the adult type may require rod placement. Patients may need neurosurgery for craniosynostosis.

Consultations

The skeletal involvement of hypophosphatasia requires consultation with an orthopedist. Patients with the infantile and childhood form should have regular follow-up appointments with their orthopedist. Evaluate adults for pseudofractures of the femur or stress fractures of the metatarsals. Refer all patients with any form of hypophosphatasia to a dental specialist. Construction of dentures may be necessary if the permanent teeth cannot be preserved. Patients may need to see a metabolic bone diseases specialist.

Diet

No special diet for hypophosphatasia is followed. Avoid vitamin and mineral supplements for rickets. The traditional defects of vitamin D metabolism are not present in hypophosphatasia, and excessive vitamin D can cause hypercalcemia and other side effects.

Activity

Gait difficulties may hamper activity in children. Although no distinct guidelines have been established, avoidance of contact sports and adequate protection of the teeth are advisable.

Medication

Drug therapy is currently not a component of the standard of care for this disease. See Treatment.

More on Hypophosphatasia

Overview: Hypophosphatasia
Differential Diagnoses & Workup: Hypophosphatasia
Treatment & Medication: Hypophosphatasia
Follow-up: Hypophosphatasia
References
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References

  1. Nishioka T, Tomatsu S, Gutierrez MA, et al. Enhancement of drug delivery to bone: characterization of human tissue-nonspecific alkaline phosphatase tagged with an acidic oligopeptide. Mol Genet Metab. Jul 2006;88(3):244-55. [Medline].

  2. Fraser D. Hypophosphatasia. Am J Med. May 1957;22(5):730-46. [Medline].

  3. Girschick HJ, Mornet E, Beer M, Warmuth-Metz M, Schneider P. Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy. BMC Pediatr. Jan 2007;7:[Medline].

  4. Millán JL, Narisawa S, Lemire I, Loisel TP, Boileau G, Leonard P, et al. Enzyme Replacement Therapy for Murine Hypophosphatasia. J Bone Miner Res. Jan 08;23:[Medline].

  5. Whyte MP, Mumm S, Deal C. Adult hypophosphatasia treated with teriparatide. J Clin Endocrinol Metab. Apr 2007;92:1203-8. [Medline].

  6. Cahill RA, Wenkert D, Perlman SA, Steele A, Coburn SP, McAlister WH, et al. Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts. J Clin Endocrinol Metab. Aug 2007;92:2923-30. [Medline].

  7. van den Bos T, Handoko G, Niehof A, et al. Cementum and dentin in hypophosphatasia. J Dent Res. Nov 2005;84(11):1021-5. [Medline].

  8. Whyte MP. The metabolic & molecular bases of inherited disease. In: Hypophosphatasia. 8th ed. 2001:5313-29.

  9. Whyte MP. Primer on the metabolic bone diseases and disorders of mineral metabolism. In: Hypophosphatasia. 5th ed. 2003:423-5.

  10. Whyte MP, Kurtzberg J, McAlister WH, et al. Marrow cell transplantation for infantile hypophosphatasia. J Bone Miner Res. Apr 2003;18(4):624-36. [Medline].

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Further Reading

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Keywords

hypophosphatasia, perinatal hypophosphatasia, infantile hypophosphatasia, childhood hypophosphatasia, adult hypophosphatasia, phosphoethanolaminuria, odontohypophosphatasia, tissue-nonspecific isoenzyme of alkaline phosphatase, TNSALP , rickets, osteomalacia, rachitic deformities, stress fractures, polyhydramnios, Bowdler spurs, severe respiratory compromise,  fever of unknown origin, anemia, bradycardia, seizures, intracranial hemorrhage, failure to thrive, hypotonia, hypoplastic lungs, craniosynostosis, hypercalcemia, osteomyelitis, pneumonia

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Contributor Information and Disclosures

Author

Horacio Plotkin, MD, FAAP, Adjunct Associate Professor of Pediatrics and Orthopedic Surgery, University of Nebraska School of Medicine
Horacio Plotkin, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Genzyme Corporation Salary Management position

Coauthor(s)

George A Anadiotis, DO, Consulting Staff, Division of Clinical and Biochemical Genetics, Department of Pediatric Rehabilitation and Development, Emmanuel Children's Hospital
George A Anadiotis, DO is a member of the following medical societies: American Medical Association and American Society of Human Genetics
Disclosure: Nothing to disclose.

Medical Editor

James Bowman, MD, Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago
James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Pathologists, American Society of Human Genetics, Central Society for Clinical Research, and College of American Pathologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Leonard G Feld, MD, PhD, MMM, Chairman of Pediatrics, Carolinas Medical Center; Chief Medical Officer, Levine Children's Hospital, Carolinas Healthcare System
Leonard G Feld, MD, PhD, MMM is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Heart Association, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplant Surgeons, Eastern Society for Pediatric Research, International Society of Nephrology, Juvenile Diabetes Foundation International, National Kidney Foundation, Society for Experimental Biology and Medicine, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

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