T-cadherin is a regulator of blood vessel remodeling and angiogenesis, involved in adiponectin-mediated protective effects in the cardiovascular system and in skeletal muscles. GWAS study has previously demonstrated a SNP in the Cdh13 gene to be associated with hypertension. However, the role of T-cadherin in regulating blood pressure has not been experimentally elucidated. Herein, we generated Cdh13^∆Exon3 mice lacking exon 3 in the Cdh13 gene and described their phenotype. Cdh13^∆Exon3 mice exhibited normal gross morphology, life expectancy, and breeding capacity. Meanwhile, their body weight was considerably lower than of WT mice. When running on a treadmill, the time spent running and the distance covered by Cdh13^∆Exon3 mice was similar to that of WT. The resting blood pressure in Cdh13^∆Exon3 mice was slightly higher than in WT, however, upon intensive physical training their systolic blood pressure was significantly elevated. While adiponectin content in the myocardium of Cdh13^∆Exon3 and WT mice was within the same range, adiponectin plasma level was 4.37-fold higher in Cdh13^∆Exon3 mice. Moreover, intensive physical training augmented the AMPK phosphorylation in the skeletal muscles and myocardium of Cdh13^∆Exon3 mice as compared to WT. Our data highlight a critically important role of T-cadherin in regulation of blood pressure and stamina in mice, and may shed light on the pathogenesis of hypertension.

Primary hyperparathyroidism (PHPT) is an endocrine disease caused by autonomous hyperproduction of parathyroid hormone by the primary altered parathyroid glands. Long-term PHPT leads to several complications, the most common being the disorders of bone metabolism and decreased bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) is the «gold standard» for detecting BMD. Parathyroidectomy remains the only method of PHPT pathogenetic treatment, resulting in independent BMD growth. Bisphosphonates, denosumab, calcimimetics, and vitamin D preparations can reduce the risk of PHPT complications, including bone complications, if surgery is impossible.

BACKGROUND: The main treatment for primary hyperparathyroidism (PHPT) is parathyroidectomy (PTE), conservative therapy, including bisphosphonates, can be used for preoperative correction of hypercalcemia, as well as to improve bone tissue condition among individuals for whom surgery should be postponed or cannot be performed due to high perioperative risks. The question of the effect of bisphosphonates on bone tissue after surgery remains open.AIM: To study the effect of preoperative bisphosphonate therapy on BMD parameters assessed in DXA and 3D-DXA in patients with PHPT one year after radical PTE.MATERIALS AND METHODS: The study was conducted on the basis of the Department of pathology of the parathyroid glands and disorders of mineral metabolism of "Endocrinology Research Center" state-funded research facility of the Ministry of Health of the Russian Federation. The study included 50 patients (2 men, 48 women), divided into two groups depending on the presence or absence of preoperative bisphosphonate (BF) therapy. The methods of DXA and 3D-DXA using 3D-Shaper Medical software were used to evaluate BMD and bone microarchitectonics. The statistical analysis was performed using the R language and the Statistica v.13 package.RESULTS: At the time of the disease’s manifestation, both groups were comparable in terms of the main indicators of calcium phosphorus metabolism, with the exception of the level of beta-crosslapse, which was higher in the group without preoperative BPh therapy (p<0,001). There were also no differences in the parameters of DXA and 3D-DXA. After surgery, both groups showed a comparable increase in BMD based on the results of DXA in the main parts of the skeleton and 3D-DXA in the femur. Changes at the level of the statistical trend were obtained for the 3D-DXA parameters, the final absolute values of which were slightly higher in the second group, including the thickness of the cortical layer in the femur as a whole and in the neck. When comparing the results of DXA before and after PTE in patients receiving BPh, statistically significant differences in absolute BMD values were obtained only in the lumbar spine (p<0,001).According to 3D-DXA data, statistically significant differences were found only in the volume of mineral density of the trabecular bone of the femur as a whole (p=0,001).When analyzing up to — in the second group, statistically significant differences in absolute BMD values were observed in the lumbar region (p<0,001), in the hip as a whole (p<0,001) and in its neck (p=0,001).According to 3D-DXA data, statistically significant differences were found in three of the eight analyzed indicators, the volume of mineral density of the trabecular bone of the femur as a whole and in the neck (p<0,001 for both), as well as the volume of mineral density of the cortical bone in the neck, (p=0,001).CONCLUSION: The 3D-DXA method allows us to evaluate not only BMD, but also its microarchitectonics, which is important for predicting the risk of fractures in patients with PHPT. Studies have shown that preoperative BPh therapy can negatively affect the recovery of BMD after PTE, especially in cortical bone tissue. Further studies are needed to confirm these data and clarify the effect of CF on the postoperative course of PHPT.

Introduction. Decreased bone mineral density (BMD) and low-energy fractures (LEF) are frequent and threatening complications of primary hyperparathyroidism (PHPT). After radical surgical treatment of PHPT, BMD recovery takes a long time, so the risk of LEF development is still elevated. Data on predictors of postoperative fractures in this cohort of patients remain very limited.Aim. To determine risk factors for the development of low-energy fractures in patients with PHPT within two years after radical surgical treatment.Materials and methods. The study group included 247 patients who underwent surgical treatment in Endocrinology Research Centre. In 2 years after surgery all patients were interviewed for the development of postoperative LEFs. The obtained data were used for comparative subgroup analysis, ROC-analysis and binary logistic regression construction.Results. Patients with postoperative LEFs were different from patients without LEFs in only one parameter – radius BMD (p = 0.0005, 0.455 [0.374; 0.501] g/cm2 vs 0.569 [0.452; 0.644] g/cm2, respectively). For this parameter, ROC analysis resulted in an AUC = 0.757 (95% CI: 0.674 to 0.841), indicating its average predictive ability. Quantitative parameters with significant difference and difference at the level of statistical trend were used in the construction of binary logistic regression. The constructed model allows predicting new LEFs with an accuracy of 94%.Conclusions. The occurrence of LEFs in patients with PHPT after radical PTE remains an actual problem; therefore, it is necessary to develop methods for their prediction and prevention. The presented mathematical model can be used as a medical decision support system for screening patients in order to exclude low-risk groups for the occurrence of LEFs in the postoperative period.

Primary hyperparathyroidism (PHPT) is a common endocrine disease with excessive secretion of parathyroid hormone and impaired mineral metabolism, resulting in decreased bone mineral density (BMD) and increased fracture risk. Radiography, dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), high-resolution peripheral QCT (HRPQCT) and radiofrequency echographic multispectrometry (REMS) have traditionally been used to assess bone density. However, these methods have certain limitations, therefore the search for new diagnostic approaches is necessary. In recent years, 3D femoral bone modelling (3D-DXA) has been actively developed, which allows three-dimensional analysis of bone density and structure based on DXA data. This method demonstrates high accuracy and correlation with CT, providing a more detailed assessment of changes in the cortical and trabecular components. The use of 3D-DXA opens new perspectives in the diagnosis and monitoring of bone complications in PHPT, which may contribute to more effective fracture risk prediction and personalised choice of therapeutic tactics.

Hyperparathyroidism is a syndrome characterized by an excessive secretion of parathyroid hormone. Etiologically, hyperparathyroidism is subdivided into primary hyperparathyroidism, which develops as a result of parathyroid adenoma, carcinoma or hyperplasia, and secondary hyperparathyroidism, which happens as a compensatory response to a hypocalcemia caused by condition outside the parathyroid glands. Turner syndrome may also be accompanied by mineral metabolism disorders of various etiology. An association of hyperparathyroidism and Turner syndrome is interesting because of multifactorial impact on bone mineral density, but only few cases of such coexistence have been previously described in the literature. This article describes two patients with Turner syndrome and hyperparathyroidism of different etiology. Hyperparathyroidism, normocalcemia, vitamin D deficiency, osteoporosis, parathyroid tumors were found in both cases. In one case a number of assays was performed to confirm the patient’s normocalcemic primary hyperparathyroidism, and surgery was performed to achieve remission. In the second case, treatment of vitamin D deficiency resulted in normalization of serum concentration of parathormone, after which the patient was prescribed antiresorptive therapy. The pathogenetic association between Turner syndrome and hyperparathyroidism requires further investigation. Comprehensive approach to the diagnosis and treatment of mineral metabolism disorders are essential for patients with coexistence of these two diseases.