There are no approved therapies for HPP. Management today consists of palliating symptoms, maintaining calcium balance and applying physical, occupational, dental and orthopedic interventions as necessary.
Due to the lack of approved treatments for HPP, patients with the disease seek symptomatic relief from multiple medical specialists depending on their symptoms (Whyte 2002):
- 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 itself37. Subcutaneous injections of salmon calcitonin also may help reduce hypercalcemia in HPP patients38 . Vitamin D sterols and mineral supplements traditionally used for rickets or osteomalacia should not be used unless there is a deficiency, as blood levels of calcium ions (Ca2+), inorganic phosphate (Pi) and vitamin D metabolites usually are not reduced39.
- Craniosynostosis, the premature closure of skull sutures, may cause intracranial hypertension and may require neurosurgical intervention to avoid brain damage in infants40.
- Bony deformities and fractures are complicated by the lack of mineralization and impaired skeletal growth in these patients. Fractures and corrective osteotomies (bone cutting) can heal, but healing may be delayed and require prolonged casting or stabilization with orthopedic hardware. A load-sharing intramedullary nail on rod has been shown to be the best surgical treatment for complete fractures, symptomatic pseudofractures, and progressive asymptomatic pseudofractures in adult HPP patients41.
- Dental problems: 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 disease42.
- Physical Impairments and Pain: Rickets and bone weakness associated with HPP can restrict or eliminate ambulation, impair functional endurance, and diminish ability to perform activities of daily living43, 44. Nonsteroidal anti-inflammatory drugs may improve pain-associated physical impairment45 and can help improve walking distance46.
Investigational use of more holistic HPP treatments has been limited.
- Bisphosphonate (pyrophosphate synthetic analog) in one infant had no discernible effect on the skeleton, and the infant’s disease progressed until death at 14 months of age47.
- Bone marrow cell transplantation in two severely-affected infants produced radiographic and clinical improvement, although the mechanism of efficacy is not fully understood and significant morbidity persisted48, 49.
- Enzyme replacement therapy with normal or ALP-rich serum from patients with Paget’s bone disease was not beneficial50, 51.
- Parathyroid hormone (PTH) 1-34 seemed to benefit one HPP adult52,but osteosarcoma in rats has precluded its use in children.
- ENB-0040, a subcutaneous enzyme replacement therapy with affinity for bone, is currently under investigation in clinical trials53.
37 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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38 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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39 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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40 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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41 Coe J.D., Murphy W.A., Whyte M.P. (1986) Management of femoral fractures and pseudofractures in adult hypophosphatasia. J Bone Joint Surg Am, 68:981-990.
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42 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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43 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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44 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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45 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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46 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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47 Deeb AA, Bruce SN, Morris AA, Cheetham TD. (2000) Infantile hypophosphatasia: disappointing results of treatment. Acta Paediatr. 89(6):730-3
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48 Whyte MP, Kurtzberg J, McAlister WH, Mumm S, Podgornik MN, Coburn SP, Ryan LM, Miller CR, Gottesman GS, Smith AK, Douville J, Waters-Pick B, Armstrong RD, Martin PL. (2003) Marrow cell transplantation for infantile hypophosphatasia. J Bone Miner Res.18(4):624-36.
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49Cahill RA, Wenkert D, Perlman SA, Steele A, Coburn SP, McAlister WH, Mumm S, Whyte MP. (2007) Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts. J Clin Endocrinol Metab. 92(8):2923-30.
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50 Whyte MP, Valdes R Jr, Ryan LM, McAlister WH. (1982) Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease. J Pediatr. 101(3):379-86.
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51 Whyte MP, McAlister WH, Patton LS, Magill HL, Fallon MD, Lorentz WB Jr, Herrod HG. (1984) Enzyme replacement therapy for infantile hypophosphatasia attempted by intravenous infusion of alkaline phosphatase-rich Paget plasma: results in three additional patients. J Pediatr. 105(6):926-33.
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52 Whyte MP, Mumm S, Deal C. (2007) Adult hypophosphatasia treated with teriparatide. J Clin Endocrinol Metab. 92(4):1203-8.
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