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 or rod is the best surgical treatment for complete fractures, symptomatic pseudofractures, and progressive asymptomatic pseudofractures in adult hypophosphatasia patients. 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 disease. Physical Impairments and pain: Rickets and bone weakness associated with hypophosphatasia can restrict or eliminate ambulation, impair functional endurance, and diminish ability to perform activities of daily living. Nonsteroidal anti-inflammatory drugs may improve pain-associated physical impairment and can help improve walking distance]
Bisphosphonate (a 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 age. 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 persisted. Enzyme replacement therapy with normal, or ALP-rich serum from patients with Paget’s bone disease, was not beneficial. Phase 2 clinical trials of bone targeted enzyme-replacement therapy for the treatment of hypophosphatasia in infants and juveniles have been completed, and a phase 2 study in adults is ongoing.
Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.In the case of less serious side effects, a patients infusion rate can be adjusted downwards until the side effects become tolerable, while in the case of more serious side effects, emergency medical attention should be sought.Immunoglobulin therapy also interferes with the ability of the body to produce a normal immune response to an attenuated live virus vaccine for up to a year, can result in falsely elevated blood glucose levels, and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection. Routes of administration
1950s – intramuscular
After immunoglobulin therapys discovery and description in Pediatrics in 1952, weekly intramuscular injections of immunoglobulin (IMIg) were the norm until intravenous formulations (IVIg) began to be introduced in the 1980s. During the mid and late 1950s, one-time IMIg injections were a common public health response to outbreaks of polio before the widespread availability of vaccines. Intramuscular injections were extremely poorly tolerated due to their extreme pain and poor efficacy – rarely could intramuscular injections alone raise plasma immunoglobulin levels enough to make a clinically meaningful difference. 1980s – intravenous
Intravenous formulations began to be approved in the 1980s, which represented a significant improvement over intramuscular injections, as they allowed for a sufficient amount of immunoglobulin to be injected to reach clinical efficacy, although they still had a fairly high rate of adverse effects (though the addition of stabilizing agents reduced this further).