Effects of Infantile Hypophosphatasia on Human Dental Tissue.

Hypophosphatasia (HPP) is an inherited, systemic disorder, caused by loss-of-function variants of the ALPL gene encoding the enzyme tissue non-specific alkaline phosphatase (TNSALP). HPP is characterized by low serum TNSALP concentrations associated with defective bone mineralization and increased fracture risk. Dental manifestations have been reported as the exclusive feature (odontohypophosphatasia) and in combination with skeletal complications. Enzyme replacement therapy (asfotase alfa) has been shown to improve respiratory insufficiency and skeletal complications in HPP patients, while its effects on dental status have been understudied to date. In this study, quantitative backscattered electron imaging (qBEI) and histological analysis were performed on teeth from two patients with infantile HPP before and during asfotase alfa treatment and compared to matched healthy control teeth. qBEI and histological methods revealed varying mineralization patterns in cementum and dentin with lower mineralization in HPP. Furthermore, a significantly higher repair cementum thickness was observed in HPP compared to control teeth. Comparison before and during treatment showed minor improvements in mineralization and histological parameters in the patient when normalized to matched control teeth. HPP induces heterogeneous effects on mineralization and morphology of the dental status. Short treatment with asfotase alfa slightly affects mineralization in cementum and dentin. Despite HPP being a rare disease, its mild form occurs at higher prevalence. This study is of high clinical relevance as it expands our knowledge of HPP and dental involvement. Furthermore, it contributes to the understanding of dental tissue treatment, which has hardly been studied so far.

Retrospective investigation of the 3D effects of the Carriere Motion 3D appliance using model and cephalometric superimposition.

OBJECTIVES: Carriere Motion 3D™ appliance (CMA) represents a method for molar distalization and correction of class II malocclusion. The aim was to investigate the 3D effects of the CMA by superimposing digital models and cephalometric X-rays. MATERIALS AND METHODS: We retrospectively examined 16 patients treated with CMA in combination with class II elastics. We compared digitized models and cephalometric X-rays of records taken before therapy and after the removal of CMA. The records were superimposed to assess the skeletal and dentoalveolar changes. The results of the cephalometric X-ray analysis were compared to an untreated age- and gender-matched sample. RESULTS: Class II occlusion was corrected after 11.85 ± 4.70 months by 3.45 ± 2.33 mm. The average distalization of the upper first molars was 0.96 ± 0.80 mm. The analysis of the cephalometric X-rays confirmed a distalization of the upper first molars with distal tipping and revealed a mesialization of the lower first molars of 1.91 ± 1.72 mm. Importantly, CMA resulted in a mild correction of the skeletal class II relationship (ANB: - 0.71 ± 0.77°; Wits: - 1.99 ± 1.74 mm) and a protrusion of the lower incisors (2.94 ± 2.52°). Compared to the untreated control group, there was significant distalization of the upper first molars and canines with mesialization and extrusion of the lower first molars. CONCLUSION AND CLINICAL RELEVANCE: CMA is an efficient method for treating class II malocclusions. However, the class II correction is only partially caused by a distalization of the upper molars.

Early enzyme replacement therapy prevents dental and craniofacial abnormalities in a mouse model of mucopolysaccharidosis type VI.

Mucopolysaccharidosis VI (MPS VI) is a hereditary lysosomal storage disease caused by the absence of the enzyme arylsulfatase B (ARSB). Craniofacial defects are common in MPS VI patients and manifest as abnormalities of the facial bones, teeth, and temporomandibular joints. Although enzyme replacement therapy (ERT) is the treatment of choice for MPS VI, the effects on the craniofacial and dental structures are still poorly understood. In this study, we used an Arsb-deficient mouse model (Arsb m/m ) that mimics MPS VI to investigate the effects of ERT on dental and craniofacial structures and compared these results with clinical and radiological observations from three MPS VI patients. Using micro-computed tomography, we found that the craniofacial phenotype of the Arsb m/m mice was characterized by bone exostoses at the insertion points of the masseter muscles and an overall increased volume of the jaw bone. An early start of ERT (at 4 weeks of age for 20 weeks) resulted in a moderate improvement of these jaw anomalies, while a late start of ERT (at 12 weeks of age for 12 weeks) showed no effect on the craniofacial skeleton. While teeth typically developed in Arsb m/m mice, we observed a pronounced loss of tooth-bearing alveolar bone. This alveolar bone loss, which has not been described before in MPS VI, was also observed in one of the MPS VI patients. Interestingly, only an early start of ERT led to a complete normalization of the alveolar bone in Arsb m/m mice. The temporomandibular joints in Arsb m/m mice were deformed and had a porous articular surface. Histological analysis revealed a loss of physiological cartilage layering, which was also reflected in an altered proteoglycan content in the cartilage of Arsb m/m mice. These abnormalities could only be partially corrected by an early start of ERT. In conclusion, our results show that an early start of ERT in Arsb m/m mice achieves the best therapeutic effects for tooth, bone, and temporomandibular joint development. As the MPS VI mouse model in this study resembles the clinical findings in MPS VI patients, our results suggest enzyme replacement therapy should be started as early as possible.

Mandibular condyle morphology among patients with mucopolysaccharidosis: An observational study of panoramic radiographs.

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of rare metabolic diseases characterized by a wide spectrum of symptoms including progressive condylar resorption. AIM: The aim of this study was to quantify the severity of condylar involvement in MPS I individuals in comparison with a group of non-MPS individuals and to describe how condylar changes may vary among the different types of MPS. DESIGN: Fifty panoramic radiographs of MPS patients (13.4 ± 6.2 years) with MPS I (n = 14), MPS II (n = 2), MPS IV (n = 8) and MPS VI (n = 2) were compared with forty panoramic radiographs of non-MPS individuals. The severity of condylar resorption was evaluated using a qualitative score (grades 0-3) and using the ratio of condylar height to ramus height (CH: RH). RESULTS: All MPS I and VI individuals showed pronounced bilateral degenerative condylar resorption. In contrast, individuals with MPS II and IV exhibited heterogeneous findings. The quantification of condylar height to ramus height revealed that CH: RH was significantly decreased in MPS I as compared to that of non-MPS individuals (P < .001). In contrast, the CH: RH ratios of MPS II and IV showed great variability. CONCLUSION: Mucopolysaccharidoses subtypes differ with regard to the severity of condylar resorption.