Histologic and ultrastructural studies on the mineralization process in hypophosphatasia

Abstract

Chondroosseous tissue from six infants with infantile hypophosphatasia and six control infants were studied by light, transmission, and scanning electron microscopy. Alkaline phosphatase histochemical reaction of the growth plate was studied in two infants and was greatly reduced when compared to two control infants. Hypertrophic chondrocytes were increased in number with persisting cartilage islets in the metaphysis. In five of the six cases studied, chondrocytes and intercartilagenous intercellular chondroid matrix appeared ultrastructurally normal. Matrix vesicle distribution was similar to that of control subjects, but they were associated with few mineral crystals. In two infants, the matrix vesicles were alkaline phosphatase nonreactive. In the calcifying zone of the growth plate and in the newly formed metaphyseal trabecular bone, cartilagenous calcospherites often were small and the orientation of crystals was nonradial when compared to that of control infants. The mineralization of diaphyseal bone appeared normal. It seems that matrix vesicles are present in hypophosphatasia and that the impaired mineralization of cartilage is due primarily to the deficiency of alkaline phosphatase. In spite of the lack of alkaline phosphatase, secondary mineralization of bone which is not mediated by matrix vesicles was normal.

Skeletal mineralization defects in adult hypophosphatasia—a clinical and histological analysis

“…Moreover, we were able to show that the calcium content within the mineralized phase was significantly lower in the cases of hypophosphatasia, an aspect of the phenotype, which has not been addressed before. Although we can only speculate whether these previously unrecognized skeletal abnormalities contribute to the increased fracture rate observed in hypophophatasia patients, we believe that our data are an important contribution to our understanding [16,21,[23][24][25][26].…”

“…From the 17 cases of adult hypophosphatasia analyzed in this study, 11 were diagnosed with osteomalacia, while five others were characterized by decreased bone remodeling. Taken together, these and other data have helped in the understanding of the skeletal manifestations of hypophosphatasia [22][23][24][25][26]. However, since there are no larger studies being performed after the standardization of bone histomorphometry by the American Society for Bone and Mineral Research [27], we decided to analyze iliac crest biopsies from eight individuals suffering from adult hypophosphatasia using non-decalcified histology, which were compared to biopsies from age-matched individuals without skeletal abnormalities or to biopsies from individuals with other types of osteomalacia.…”

Tissue-nonspecific alkaline phosphatase deficiency causes abnormal craniofacial bone development in the Alpl−/− mouse model of infantile hypophosphatasia

“…These results are not entirely surprising because TNAP is expressed in pre-hypertrophic and hypertrophic chondrocytes [6], and abnormal metaphyseal growth plates are seen in patients with HPP and in Alpl −/− mice [6,10,58,59]. It is worth noting here that hypertrophic zone expansion in long bones is characteristic of multiple forms of rickets [60-62].…”

Hypophosphatasia associated with Pseudotumor cerebri and respiratory insufficiency

“…Severe forms of the disease (perinatal and infantile) are transmitted as an autosomal recessive trait, while the mode of inheritance of clinically more mild childhood hypophosphatasia or adult hypophosphatasia remains uncertain, and both autosomal recessive and autosomal dominant transmission have been suggested. 2,3 Infantile hypophosphatasia, which is recognized before 1 year of age, has clinical manifestations such as severe bony hypomineralization, hypercalcemia, hypercalciuria, and nephrocalcinosis. The mortality rate is approximately 50%, and patients die usually due to respiratory infections.…”