Hypophosphatasia (HPP) is an inherited disease caused by genetic mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). This results in defects in bone and tooth mineralization. We recently demonstrated that TNALP-deficient (Akp2−/−) mice, which mimic the phenotype of the severe infantile form of HPP, can be treated by intravenous injection of a recombinant adeno-associated virus (rAAV) expressing bone-targeted TNALP with deca-aspartates at the C-terminus (TNALP-D10) driven by the tissue-nonspecific CAG promoter. To develop a safer and more clinically applicable transduction strategy for HPP gene therapy, we constructed a self-complementary type 8 AAV (scAAV8) vector that expresses TNALP-D10 via the muscle creatine kinase (MCK) promoter (scAAV8-MCK-TNALP-D10) and examined the efficacy of muscle-directed gene therapy. When scAAV8-MCK-TNALP-D10 was injected into the bilateral quadriceps of neonatal Akp2−/− mice, the treated mice grew well and survived for more than 3 months, with a healthy appearance and normal locomotion. Improved bone architecture, but limited elongation of the long bone, was demonstrated on X-ray images. Micro-CT analysis showed hypomineralization and abnormal architecture of the trabecular bone in the epiphysis. These results suggest that rAAV-mediated, muscle-specific expression of TNALP-D10 represents a safe and practical option to treat the severe infantile form of HPP.

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Major bleeding associated with sagittal split ramus osteotomy (SSRO) involves vessels such as the inferior alveolar, facial, and maxillary arteries and veins, and the retromandibular vein (RMV). The present study aimed to clarify and classify the three-dimensional variations in RMV position and course direction in relation to the mandible. Specimens comprised a total of 15 scientific cadavers, and the relationship between RMV and the mandible lateral and posterior views was observed. We identified 3 patterns on the lateral view, the mean distance between the RMV and the posterior border of the ramus was 3.9 mm at the height of the lingula. A total of five course patterns were identified on the posterior view. In no course pattern, the RMV inferior to the lingula was lateral to its position superior to the lingual. The present findings suggest that it may be possible to predict correlations with intraoperative bleeding risk. Further study is planned using contrast computed tomography in patients with jaw deformity for skeletal classification.

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Recent research on osteoporosis has led to a number of advances in our understanding of its pathophysiology and treatment. However, much is still unknown, and a consensus is yet to be reached on how osteoporosis affects the jaw. With this in mind, the present study sought to identify changes over time in the mandibular cancellous bone of senile osteoporotic mice by assessing the trabecular structure in their mandible and tibia. The senescence-accelerated mouse strain P6 (SAMP6) (n = 5) was used as the experimental model, whereas the senescence-accelerated mouse strain R1 (SAMR1) served as control (n = 5). All mice were aged 16 weeks. Bone morphometry was performed by taking a series of micro-computed tomography (micro-CT) scans of the same animal at different time points. As a result, the morphometric parameters of bone volume fraction (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) in the tibias of the SAMP6 mice were significantly lower than those of the SAMR1 mice. Conversely, there were no consistent differences in these parameters in the jaw bones of SAMP6 or SAMR1 mice. These findings may suggest that relevant load-bearing teeth protect the alveolar bone structure from the degenerative effects of osteoporosis.