Рис. 3. Механизмы, приводящие к повышенному риску переломов при СД2.

Fracture risk is significantly increased in both type 1 and type 2 diabetes and individuals with diabetes experience worse fracture outcomes compared to normoglycemic individuals. Patients with T1DM have decreased bone mineral density (BMD), whereas patients with T2DM demonstrate increased BMD compared to healthy control. The latest studies show increased incidence of low-traumatic fractures in patients with T2DM instead of high bone mineral density (BMD). The risk of osteoporotic fractures in patients with T2DM can be explained by disease complications and increased risk of falls and consequent trauma. However, the most important cause of bone fragility in T2DM is the deterioration in bone microarchitecture, the mechanism of which is not completely understood. High BMD in patients with T2DM does not allow us to use dual-energy X-ray-absorptiometry as a “gold standard” test for diagnosticsof osteoporosis. Consequently,new risk factors and diagnostic algorithm as well as treatment strategy should be developed for patients with T2DM. In addition to this, some researchers considered that the group of T2DM is geterogenous and physicians might face patients with osteoporosis and mild diabetes that add very little to bone fragility; patients with osteoporosis and moderate or severe diabetes which also affects bone tissue –diabetoosteoporosis; and patients without osteoporosis but severe diabetes which cause bone tissue deterioration with the development of diabetic bone disease. New diagnostic tools and algorithm and new experimental research are needed for better understanding bone deterioration in patients with T2DM. This review summarizes our current knowledge on fracture rate, risk factors for fractures and causes of bone deterioration in subjects with T2DM

Hereditary syndromes with signs of premature aging

Aging is a multi-factor biological process that inevitably affects everyone. Degenerative processes, starting at the cellular and molecular levels, gradually influence the change in the functional capabilities of all organs and systems. Progeroid syndromes (from Greek. progērōs prematurely old), or premature aging syndromes, represent clinically and genetically heterogeneous group of rare hereditary diseases characterized by accelerated aging of the body. Progeria and segmental progeroid syndromes include more than a dozen diseases, but the most clear signs of premature aging are evident in Hutchinson-Guilford Progeria Syndrome and Werner Syndrome. This review summarizes the latest scientific data reflecting the etiology and clinical picture of progeria and segmental progeroid syndromes in humans. Molecular mechanisms of aging are considered, using the example of progeroid syndromes. Modern possibilities and potential ways of influencing the mechanisms of the development of age-related changes are discussed. Further study of genetic causes, as well as the development of treatment for progeria and segmental progeroid syndromes, may be a promising direction for correcting age-related changes and increasing life expectancy

Osteogenesis imperfecta as a cause of death

Osteogenesis imperfecta (OI) is a rare heterozygous connective tissue disordercaused by mutations in genes that affect collagen components (in most cases mutations in COL1A1 и COL1A2 genes). The current classification system includes 15 types of OI, one of which (type II) is characterized by 100% intrauterine or perinatal mortality. The structure of mortality in other OI types is poorly understood because of the heterogeneity of clinical symptoms and the severity of connective tissue damage. W present a clinical case of type III osteogenesis imperfecta, complicated by generalized osteoporosis with multiple fractures of vertebrae and tubular bones and progressive kyphoscoliosis. Late-initiated treatment led to progression of the disease and led to cardiopulmonary insufficiency and death of the patient. Our clinical case highlights the importance of timely diagnosis, treatment and regular observation in patients with OI

Evaluation of diagnostic potential of the collagen osteogenesis marker (P1NP) compared with osteocalcin in Cushing’s disease

Background: Secondary osteoporosis is a significant problem, especially in patients with endocrine pathology, which is not accompanied constantly by distinct clinical symptoms. Markers of bone origin are needed, which could be used in osteoporosis diagnosis to clarify its genesis, especially in young people who have secondary osteoporosis more often than older patients. In Cushings disease (CD), such a marker, in addition to osteocalcin, could be another bone formation marker, procollagen type 1 N-terminal propeptide (P1NP). Aims: To study the diagnostic potential of P1NP as an additional marker of endogenous hypercortisolism (Cushings disease) compared to osteocalcin. Materials and methods: The study involved patients with Cushings disease and healthy volunteers, matched by gender, age, and body mass index. The levels of osteocalcin and P1NP were assessed in both groups, the electrochemiluminescence method for P1NP (Cobas e411 (Roche, Switzerland)) and for osteocalcin (Cobas 6000 Module e601 (Roche, Switzerland)) was used. ROC analysis was performed with the calculation of sensitivity and specificity of the method to determine the cut-off point for P1NP in CD diagnosis. Results: 29 patients with Cushings disease and 27 healthy individuals from the control group were included in the study. There were no differences in age, sex and body mass index (p = 0.488, 0.426 and 0.531, respectively). Both studied bone formation markers (osteocalcin and P1NP) were reduced in patients with CD: 8.53 ng/ml (Q25%;Q75% 5.40; 12.41) versus 22.45 ng/ml (Q25%;Q75% 17.36; 26.31) (p 0.001) and 28.50 ng/ml (Q25%;Q75% 18.00; 44.00) versus 56.50 ng/ml (Q25%;Q75% 39.50; 65.50) (p 0.001), respectively. The area under the receiver operating characteristic curve (AUC) was 0.808 (95% CI 0.6930.924) for P1NP and 0.925 (95% CI 0.8570.992) for osteocalcin, that indicates the greater diagnostic value of osteocalcin for CD verification in healthy controls. Optimal cut-off points were obtained: 53.4 ng/ml (values below are more typical for patients with CD; sensitivity of the method is 96.55%, specificity 57.69%) for P1NP and 15.285 ng/ml (below for patients with CD; sensitivity was 92.59%, specificity 77.78 %) for osteocalcin. Conclusions: The diagnostic potential of osteocalcin to detect Cushings disease in the population is higher compared to P1NP. However, applying of P1NP can be useful because, unlike osteocalcin, it is a direct indicator of the formation of bone matrix collagen structures, that is important for assessing the degree of inhibition of collagen type 1 synthesis in CD and deterioration of bone tissue due to glucocorticoid-induced osteoporosis

Sclerostin antibodies as novel anabolic therapy for osteoporosis

Osteoporosis medications are dividedinto two groups: those inhibiting bone resorption and formation (bisphosphonates and denosumab), and those stimulating bone formation i.e. having an anabolic effect. The latter include teriparatide, parathyroid hormone 1-84 and abaloparatide, all of which stimulate bone resorption as well as bone formation, which limits their anabolic effect. The discovery of sclerostin the key inhibitor of bone formation has led to development of the concept that inhibition of this protein could stimulate bone formation. Romosozumab is a human monoclonal antibody to sclerostin that binds to sclerostin and enables Wnt-signaling pathway ligands and their co-receptors to interact with each other, which, in turn, leads to increased bone formation and bone mineral density. Unlike classical anabolic drugs in osteoporosis treatment, romosozumab stimulates bone formation and inhibits bone resorption. In clinical trials, romosozumab showed marked increase in lumbar spine and hip bone mineral density. Presented article contains information about pre-clinical and clinical studies of romosozumab

Treatment of severe idiopathic hypoparathyroidism: a case report

Hypoparathyroidism is a rare disorder characterized by parathyroid hormone (PTH) insufficiency, the development of hypocalcemia and alteration of bone tissue remodeling. The goal of treatment is to normalize the indicators of calcium-phosphorus metabolism and leveling of clinical manifestations. Standard treatment of hypoparathyroidism consists of oral calcium and active forms of vitamin D, in doses necessary to maintain calcium levels at the lower limit of the reference interval. Nevertheless, treatment of the disease exerts certain difficulties in clinical practice. At the same time, compensation of the hypoparathyroidism is necessary to prevent ectopic calcification. Daily subcutaneous delivery of PTH (184) and PTH (134) has emerged as a promising therapeutic tool. However, its use should be restricted to patients insufficiently controlled with the standard treatment with active vitamin D and calcium. We present a clinical case of idiopathic hypoparathyroidism with severe clinical presentation of hypocalcaemia and ectopic calcification. Idiopathic hypoparathyroidism is a consequence of autoimmune destruction of the parathyroid glands and is exhibited by excluding all known causes of hypoparathyroidism. PTH (134) treatment allowed reducing the dose of calcium and vitamin D and achieving compensation of the disease

Case report of Sagliker syndrome in a young patient with secondary hyperparathyroidism and chronic renal failure

Sagliker syndrome is a rare complication of renal osteodystrophy, characterized by severe skeletal and cranium deformities, neurologic and soft tissue abnormalities in patients with chronic renal failure (CRF) and untreated secondary hyperparathyroidism. This article reports a 29-year-old female patient with end-stage CRF after 9 years of hemodialysis. She had severe secondary hyperparathyroidism, hyperplasia of three parathyroid glands and cranium and skeletal bone structure deformation. The first changes appeared after 4 years of therapy with peritoneal dialysis. They included uglifying face appearances, short stature, severe maxillary changes, chest deformity. During the examination we revealed severe tomographical and X-ray changes: maxillary and mandibular hyperplasia, temporomandibular articulation changes, affected cheekbones, sphenoid bone and bones of the cranial vault, fingertip changes, vertebral body compression. Although surgical parathyroidectomy was effective at biochemical abnormalities, severe bone deformities were not regressed. This case highlights the importance of clinicians attention for early monitoring and appropriate treatment of secondary hyperparathyroidism in patients with end-stage CRF

Dynamics of NT-proBNP and ST2 levels as markers of heart failure in patients with endogenous Cushing syndrome (hypercortisolism)

Aim. To evaluate frequency of heart failure syndrome in patients with endogenous hypercortisolism and to establish relationship between effective treatment for hypercortisolism and regression of heart failure with particular emphasis on the observation of NT-proBNP and ST2 levels. Materials and methods. 56 patients with endogenous hypercortisolism (45 female, mean age 47 years [36; 55] hospitalized with endogenous hypercortisolism to National Medical Research Center for Endocrinology were enrolled in the study. All patients underwent comprehensive clinical investigation including expert echocardiography with speckle tracking and evaluation of NT-proBNP and ST2 cardiac biomarkers at baseline and 6 months after surgical treatment. Results. According to clinical data and elevated biomarkers of cardiac stress 28 out of 56 patients (50%) at baseline met the criteria for heart failure. 20 patients were included in the final analysis. Follow-up investigation with focus on changes in NT-proBNP and ST2 levels demonstrated that surgical correction of endogenous hypercortisolism resulted in resolution of heart failure syndrome in 11 patients (55%). Conclusion. These preliminary data suggest that signs and symptoms of heart failure are observed in patients with endogenous hypercortisolism in about half the cases. Surgical correction results in resolution of heart failure in approximately two thirds of the cases. Prospective evaluation NT-proBNP and ST2 levels may provide important diagnostic and prognostic information in patients with endogenous hypercortisolism

Rare genetic diseases of the bone tissue: the case of a family with osteogenesis imperfecta and X-linked hypophosphataemia

Osteogenesis imperfecta (OI) and X-linked hypophosphataemia (XLH) are rare genetic diseases, which lead to childhood-onset bone fragility, low-trauma fractures and limb deformities. OI occurs as a result of impaired type 1 collagen synthesis at different stages, depending on the type of a genetic mutation, which leads to bone strength impairment. In most cases OI is a disorder with an autosomal dominant inheritance. However, there are also cases of autosomal recessive inheritance. To date, 16 types of OI are distinguished, with type 2 being the most severe due to 100% mortality rate in neonatal and perinatal periods. XLH is characterized by altered bone mineralization due to impaired phosphorus absorption and reabsorption, as a result of mutations in the PHEX gene. The bone tissue softens, and this process is accompanied by deformities in long tubular bones. In this article we describe the family, in which both diseases are presented, despite their rarity. The case is investigated from points of view: the clinicians and the patients perspective

First description of a type v osteogenesis imperfecta clinical case with severe skeletal deformities caused by a mutation p.119C> T in IFITM5 gene in Russia

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder. Main clinical manifestations include recurring pathological fractures and progressive skeletal deformation. Five types of OI are distinguished based on clinical symptoms. In most cases, the disease is caused by mutations in the COL1A1 and COL1A2 genes, leading to a defect of type 1 collagen synthesis, which is the main component of the bone matrix. Up to 5% of patients with OI have a mutation in IFITM5 gene, which leads to the development of OI type V. Approximately 150 cases of the OI type V are described in the literature, and mutation c.-14C T in IFITM5 gene is found in most of the cases. Only 5 patients have a c.119C T: p.S40L.mutation. Pathogenesis of OI type V is not fully understood. It is assumed that mutations in the IFITM5 gene cause impaired osteoblastogenesis, decreased bone mineral density and multiple low-traumatic fractures. There is probably a phenotype-genotypic correlation in cases with different mutations of the IFITM5. However, it is currently difficult to assess the relationship in view of the variability of the characters and the low prevalence of the OI type V. We present the first description in Russia of the clinical case of an adult patient with OI type V due to a rare mutation p.119C T: p.S40L in the IFITM5 gene