Orthodontic force induces local bone resorption in mild-type hypophosphatasia mouse model

Objectives Hypophosphatasia (HPP) is a congenital disease caused by mutations in the tissue non-specific alkaline phosphatase gene. HPP is characterized by impaired hard tissue mineralization and premature tooth loss. Mild-type HPP includes childhood-, adult, and odonto-HPP. Mild-type HPP is difficult to diagnose because individuals with mild-type HPP do not have characteristic symptoms. The effects of applying mechanical stress, such as that caused by orthodontic force, on the teeth and jawbones of patients with mild-type HPP are unknown; therefore, in this study these effects were examined in mild-type HPP model mice. Methods A 10 gf nickel–titanium closed-coil spring was placed on the maxillary incisors and left first molar (M1) of mild-type HPP model mice ( Akp2 +/- ). The M1 moved mesially to the maxillary incisors 14 days before sampling. Results Tooth movement distance, serum alkaline phosphatase (ALP) and serum C -terminal telopeptide of Type I collagen (CTX-1) levels did not differ between Akp2 +/− and normal ( Akp2 +/+ ) mice. However, alveolar bone resorption on the compressed side was higher in Akp2 +/− mice than that in normal mice. The cancellous bone quality on the compressed was side was lower in Akp2 +/− than in Akp2 +/+ mice. Fibrous structures infiltrated the bone resorption sites, and the number of osteoclasts was markedly higher in Akp2 +/− mice. Conclusions The application of orthodontic force to mice with mild-type HPP did not affect the serum ALP and bone resorption marker CTX-1 levels, or tooth movement. However, compression induced alveolar bone resorption due to an increase in osteoclasts. These findings support the importance of differentially diagnosing mild-type HPP before initiating treatment.