Administration of Bisphosphonate Preparations to Mice with Mild-type Hypophosphatasia Reduces the Quality of Spontaneous Locomotor Activity

Hypophosphatasia (HPP) is a congenital bone disease caused by tissue-nonspecific mutations in the alkaline phosphatase gene. It is classified into six types: severe perinatal, benign prenatal, infantile, pediatric, adult, and odonto. HPP with femoral hypoplasia on fetal ultrasonography, seizures, or early loss of primary teeth can be easily diagnosed. In contrast, pediatric, adult, and odonto types of HPP over 4 years of age are less likely to be diagnosed because they do not have typical symptoms. Consequently, it may be misdiagnosed as common osteoporosis, and treatments incompatible with HPP may be implemented. The purpose of this study was to analyze the effects of bisphosphonate preparations administration on the femur of Akp2^+/- mice, a mild-type HPP mice model. Zoledronic acid (Zol) was subcutaneously administered to 4-week-old Akp2^+/- mice at 1 mg/kg (volume: 200 μL) once a week for a total of 5 times. Afterward, spontaneous locomotor activity analysis was performed, and serum and femur bones were collected at 9 weeks of age. Additionally, micro-computed tomography (CT) analysis, histological analysis, and analysis of the expression levels of various marker proteins and genes were performed. Age-matched Akp2^+/+ mice served as controls. The results demonstrated that the administration of Zol to Akp2^+/- mice, compared to Akp2^+/+ mice, insufficiently promotive bone formation, torn femoral head cartilage, and decreased spontaneous locomotor activity. Therefore, it is important to accurately diagnose patients with mild-type HPP.