Atypical femur fractures: a distinctive tract of adult hypophosphatasia.

Abstract

Hypophosphatasia (HPP) is a congenital, rare and heterogeneous bone disorder, characterized by a deficit of calcified tissue mineralization, leading to skeletal deformities and osteomalacia in adults, rickets in infants and children, and fragility fractures and premature loss of dentition in children and adults. The disease is caused by a reduced or absent expression and activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, derived from inactivating mutations of the alkaline phosphatase (ALPL) gene. Six different clinical variants have been reported, defined by the onset age and characterized by different degrees of severity. The adult form of HPP presents a wide range of clinical manifestations, many of which are non-specific, mild, and often overlapping with other metabolic bone diseases. Consequently, many cases of adult HPP are, commonly, undiagnosed or misdiagnosed, and, subsequently, wrongly or non-treated with severe consequences for patients and a very negative impact on their quality of life and life expectancy, as well as with costs due to the administration of wrong therapies and treatments of their side effects. The occurrence of a fragility atypical femur fracture in the adulthood can be suspected as a clinical indication of an undiagnosed adult mild form of HPP; and the presence of at least one of this kind of fracture can help in the diagnosis of adult HPP, together with conventional HPP biochemical signs.