Hypophosphatasia (HPP) Treatment & Management

Updated: Aug 07, 2019
  • Author: Ricardo R Correa Marquez, MD, EsD, FACP, FACE, FAPCR, CMQ, ABDA, FACHT; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
  • Print
Treatment

Medical Care

Enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase, or asfotase alfa (Strensiq), was approved by the FDA in 2015 and is used as first-line therapy in infants, children, and some adults with HPP. The drug may be used in addition to supportive care to decrease the morbidity associated with the disease. [13]

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. [15, 16] One patient was reported with improved bone mineralization after starting enzyme replacement with recombinant asfotase alfa (ALP) from 1 day after birth. [17]

A long-term study of asfotase alfa demonstrated improved bone mineralization, respiratory function, and survival rate in 73 patients with perinatal and infantile HPP compared with 48 historical controls. Suggested indications for asfotase alfa treatment in adults include a history of childhood involvement (before age 18 years) and one or more of the following:

  • Musculoskeletal pain requiring prescription pain medications
  • Disabling polyarthropathy or chondrocalcinosis
  • Major low-trauma fracture attributable to HPP (spine, hip, humerus)
  • Delayed or incomplete fracture healing or fracture nonunion
  • Repeated orthopedic surgeries to treat complications of HPP
  • Disabling functional impairment that affects mobility, gait, and activities of daily living (ADL)
  • Low bone marrow density on dual X-ray absorptiometry (DXA)
  • Radiological evidence of nephrocalcinosis

Currently, there are no guidelines for selecting adult patients with HPP for treatment, evaluating results of treatment, or determining optimal duration of treatment. [13, 18, 19]

In a study of 10 adult patients with HPP, teriparatide was administered to increase osteoblast production of ALP. Effects of treatment on bone marrow density (BMD) varied, although the study reported improved pain, mobility, and fracture repair in some cases. [20] Another study involving six postmenopausal women with HPP showed that teriparatide treatment decreased pain, but no response was seen in one premenopausal woman. [21]

A study involving eight adult patients with HPP treated with monoclonal anti-sclerostin antibody found that treatment for 29 weeks increased bone formation markers and transiently decreased C-telopeptide levels. Lumbar spine BMD showed a mean increase of 3.9% at the end of the study. [22]

Antiresorptive agents such as bisphosphonates are contraindicated, as they may further lower ALP and are harmful in patients with HPP.                                                                                                                                    

Adult pseudofractures may require orthopedic care to heal properly. A dentist should closely monitor all individuals with hypophosphatasia.

Although HPP is a physical disease, several studies have found that mental health can also be affected. [1, 23]

Various other treatments have been attempted, including zinc, magnesium, cortisone, and plasma. The results have not been encouraging with these older therapies.

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. [24] 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. [25]

Next:

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, fractures, pseudofractures, and bone deformities may require rod placement. Patients may need neurosurgery for craniosynostosis.

Previous
Next:

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 should see a metabolic bone diseases specialist.

Previous
Next:

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. Patients should also avoid energy drinks.

Previous
Next:

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.

Previous