Hypophosphatasia Treatment & Management
- Author: Horacio B Plotkin, MD, FAAP; Chief Editor: Luis O Rohena, MD more...
The FDA approved asfotase alfa (Strensiq) in 2015 as the first therapy for hypophosphatasia caused by a rare hereditary mutation in alkaline phosphatase gene. The drug may be used in addition to supportive care to decrease the morbidity associated with the disease. 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. Various treatments have been attempted, including zinc, magnesium, cortisone bisphosphonates, and plasma. The results have not been encouraging with these older therapies.
Approval of asfotase alfa was based on four prospective, open-label studies involving 99 patients who developed hypophosphatasia in utero, as an infant, or as a juvenile. They received the drug for up to 6.5 years. Patients with either perinatal or infant onset of the disease who were treated with asfotase alfa showed improvement in overall survival, as well as ventilator-free survival. Ninety-seven percent of patients receiving the drug were alive at age 1 year compared with 42% of control patients selected from a natural history study group. The ventilator-free survival rates for both groups followed much the same pattern. Patients with juvenile-onset hypophosphatasia also experienced improved growth and bone health compared with patients in a natural history database.[7, 8]
One patient was reported with improved bone mineralization after starting enzyme replacement with recombinant asfotase alfa (ALP) from 1 day after birth.
Enzyme replacement from birth in TNALP knockout mice using bone-targeted, recombinant human TNALP prevented the disease. Targeted enzyme replacement therapy is currently being tested in humans.[7, 11, 12, 13]
Response to teriparatide treatment was seen in terms of decreased pain in 6 postmenopausal women, and no response was seen in 1 premenopausal woman.
Evidence also suggests 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. The effects of bone marrow transplant in hypophosphatasia appear to be transient, as bone lesions may recur approximately 6 months after the transplantation. 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.
Vitamin B-6 may be indicated to treat neonatal seizures.
Orthopedic surgical involvement may be necessary in patients with hypophosphatasia. Rachitic deformities and gait abnormalities require orthopedic evaluation. For them to heal completely, fractures, pseudofractures, and bone deformities may require rod placement. Patients may need neurosurgery for craniosynostosis.
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 should see a metabolic bone diseases specialist.
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.
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.
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