Hypophosphatasia (HPP) is one of the congenital bone systems diseases in which mutations in the tissue-nonspecific alkaline phosphatase gene. It is classified into six types, perinatal severe, prenatal benign, infantile, childhood, adult, and odonto type HPP. HPP with femoral hypoplasia on fetal echography and premature tooth loss is easy to diagnose. In contrast, childhood over 4 years of age, adult, and odonto type HPP are not diagnostic of HPP, because they do not have typical symptoms. As a result, HPP cannot be diagnosed, so it is considered to be general osteoporosis or periodontal disease. The purpose of this study was to analyze the effects of administration of BP preparations on the femur of Akp2^+/- mice, which are mild HPP model mice.
Zoledronic acid (Zol) was subcutaneously administered at 1 mg/kg (vol: 200 μL) every other week for a total of 5 times to 4-week-old Akp2^+/- mice. One week later, the femurs were sampled and HE staining was performed for micro-CT analysis and histological analysis. As a control, Akp2^+/+ mice of the same age were used.
In the femoral head, degeneration of cartilage, invasion and destruction of fibers were confirmed only in Akp2^+/- mice after administration of Zol. Activity analysis result, only the Zol-administered Akp2^+/- mice showed lower values than the other mice in all items.
Our results suggest that administration of Zol formulations to patients with mild HPP may increase the risk of exacerbation of symptoms compared to healthy subjects. Consequently, it is important to accurately diagnose mild HPP patients.