There are no approved therapies for hypophosphatasia (HPP). Management today consists of palliating symptoms, maintaining calcium balance and applying physical, occupational, dental and orthopedic interventions as necessary.
Living with HPP
Due to the lack of approved treatments for HPP, management focuses on supportive therapy to minimize disease-associated symptoms, and family support is important.
Care for infants may include respiratory support, treatment of hypercalcemia/hypercalciuria, treatment of seizures with vitamin B6, and surgical treatment of craniosynostosis.
All patients living with HPP should seek routine dental care starting at one year of age and may benefit from non-steroidal anti-inflammatory drugs (NSAIDS) for osteoarthritis and bone pain, and bone rods for pseudofractures and stress fractures. Patients with infantile HPP should be monitored for increased intracranial pressure caused by craniosynostosis. Patients should also avoid bisphosphonates and excess vitamin D.
Learn more about managing HPP.
Orthopedic Care
All HPP patients with bone symptoms may benefit from consulting an orthopedist (a doctor who specializes in the musculoskeletal system).
| Orthopedic surgical involvement may be necessary. Bone deformities and fractures are complicated by the lack of mineralization and impaired skeletal growth in patients. Fractures and corrective osteotomies (bone cutting) can heal, but healing may be delayed and require prolonged casting or stabilization with orthopedic hardware. Craniosynostosis, the premature closure of skull sutures, may cause intracranial hypertension and may require neurosurgical intervention to avoid brain damage in infants.15 |
 Orthopedic hardware may be required for severe fractures |
Dental Care
All patients should consult with a dental specialist starting at one year of age. Children particularly benefit from skilled dental care, as early tooth loss can cause malnutrition and inhibit speech development. Dentures may ultimately be needed. Dentists should carefully monitor patients’ dental hygiene and use prophylactic programs to avoid deteriorating health and periodontal disease.
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Diet and Supplements
Hypercalcemia in infants may require restriction of dietary calcium or administration of calciuretics. However, this should be done carefully so as not to increase the skeletal demineralization that results from the disease itself.
17 Subcutaneous injections of salmon calcitonin also may help reduce hypercalcemia in HPP patients.
18 Vitamin D sterols and mineral supplements traditionally used for rickets or osteomalacia should not be used unless there is a deficiency.
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Physical Activity
Rickets and bone weakness associated with HPP can restrict or eliminate ambulation, impair functional endurance, and diminish ability to perform activities of daily living.
20, 21 Nonsteroidal anti-inflammatory drugs may improve pain-associated physical impairment
22 and can help improve walking distance.
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Investigational Treatment
The investigational use of more definitive HPP treatments has been limited. A subcutaneous enzyme replacement therapy has demonstrated potential in preclinical studies and is currently under investigation in clinical trials.
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15 Collmann H, Mornet E, Gattenlöhner S, Beck C, Girschick H. (2009) Neurosurgical aspects of childhood hypophosphatasia. Childs Nerv Syst. 25(2):217-23.
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16 Reibel A., Maniere M., Class F., Droz D., Alembik Y., Mornet E., Bloch-Zupan A. (2009) Orodental phenotype and genotype findings in all subtypes of hypophosphatasia. Orphanet J Rare Dis, 4:6.
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17 Whyte M.P., Magill H.L., Fallon M.D., and Herrod H.G. (1986) Infantile hypophosphatasia: normalization of circulating bone alkaline phosphatase activity followed by skeletal remineralization. Evidence for an intact structural gene for tissue nonspecific alkaline phosphatase. J Pediatr,108:82-88.
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18 Barcia J.P., Strife C.F., Langman C.B. (1997) Infantile hypophosphatasia: treatment options to control hypercalcemia, hypercalciuria, and chronic bone demineralization. J Pediatr,130: 825.
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19 Opshaug O., Maurseth K., Howlid H., Aksnes .L, Aarskog D. (1982) Vitamin D metabolism in hypophosphatasia. Acta Paediatr Scand, 71(3):517-21.
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20 Girschick H.J., Schneider P., Haubitz I., Hiort O., Collmann H., Beer M., Shin Y.S., Seyberth H.W. (2006) Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. Orphanet J Rare Dis, 28:1-24
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21 Girschick H.J., Mornet E., Beer M., Warmuth-Metz M., Schneider P. (2007) Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy. MC Pediatrics, 7:3.
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22 Girschick H.J., Schneider P., Haubitz I., Hiort O., Collmann H., Beer M., Shin J.S., Seyberth H.W.. (2006) Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. Orphanet J Rare Dis, 1:24.
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23 Girschick H.J., Seyberth H.W., Huppertz H.I. (1999) Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs. Bone, 25:603-7.
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24 Girschick H.J., Seyberth H.W., Huppertz H.I. (1999) Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs. Bone, 25:603-7.
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