Vol 21, No 1 (2018)

Original study
Progress of osteoporosis: stratification of fracture risk
Nikitinskaya O.A., Toroptsova N.V.

Background: There are two approaches to identify candidates for the prescription of osteoporosis treatment: identification of patients with low bone mineral density using DEXA of the axial skeleton and calculation of the 10-year probability of major osteoporotic fractures using FRAX®.

Aims: to assess the diagnostic accuracy of different FRAX® thresholds in the Russian population.

Materials and methods: the value of individual 10-year probability of osteoporotic fracture by FRAX® at the time of inclusion in the study was retrospectively estimated in 224 postmenopausal women, whom the major osteoporotic fractures were recorded over 10 years of prospective observation. The diagnostic accuracy of different thresholds were compared: "European" and Russian age-dependent thresholds, fixed 20% threshold, the average FRAX® of patients who had a major osteoporotic fracture during follow-up (16%), FRAX® value corresponding to the "cut-off point" (12,5%).

Results: The Russian FRAX model showed the acceptable diagnostic accuracy of the method (AUC=0.665±0.036; 95% CI 0.595; 0.736). The "European" threshold of therapeutic intervention demonstrated 72% sensitivity and 38% specificity, 20% threshold – 27% and 87%, the Russian threshold – 41% and 77%, 12.5% threshold – 68% and 58%, 16% threshold – 57% and 73%, respectively. The diagnostic precision of the specified thresholds was 54%, 58%, 60%, 63% and 65%, respectively.

Conclusions: the Russian age-dependent threshold remains the optimal way to decide whether to initiate anti-osteoporotic therapy based on an assessment of the 10-year probability of fracture by the Russian model for FRAX®.

Osteoporosis and Bone Diseases. 2018;21(1):4-9
Factors influencing bone mineral density in postpartum women
Novikova T.V., Kuznetsova L.V., Yakovleva N.Y., Zazerskaya I.E.

Background: Osteopenia is a common condition. Therefore, identification of groups for prevention of osteoporosis and restoration of bone mineral density (BMD) remains relevant.

Aim: to assess the factors contributing to development of osteopenia in puerperas.

Methods: prospective cross-sectional study. We examined 112 patients aged 20-35, 3-5 days after delivery. To assess possible factors for BMD decrease, we analyzed medical history, lifestyle, nutrition, anthropometric data, obstetric and gynecological history, and pregnancy course. We also assessed serum levels of 25-hydroxycalciferol (25-OH-D) and PTH. BMD was measured by dual energy x-ray osteodensitometry. We considered Z-score from -1 to -2.5SD as osteopenia, below -2.5 SD-as osteoporosis.

Results: based on Z-score values, two groups were formed: 1 (n=70) - puerperas with osteopenia, 2 (n=42) - puerperas with normal BMD. In the first group, osteopenia in the distal radius was observed in 48%, in the lumbar spine in 16% and in the proximal femur in 36%. Influence of the following possible factors in group 1 was established: BMI in 15-20 years ≤ 18 kg/m2 (p<0.013), BMI ≥ 25 kg/m2 (p<0.018), 25-OH-D less than 25 ng / ml (p < 0.0018), calcium intake less than 800 mg/day (p<0.041). Menstrual disorders (p<0.052) and preeclapsia (p < 0.042) affected lumbar spine BMD. In group 1, vitamin D deficiency was detected in 82% of women, 18% showed vitamin D insufficiency; in group 2, vitamin D deficiency was found in 16%, deficiency in 70%, in 14% vitamin D was normal. In women with a combination of factors such as BMI≤ 18 kg/m; calcium intake lower than 800 mg/day, menstrual cycle disorders, vitamin D deficiency - osteopenia in the distal radius occured 11 times more often (OR=11,47059; CI 95%=[4,0326; 32,627]).

Conclusion: most significant impact on BMD decrease in puerperas can be expected if patient has the following risk factors: BMI≤18 kg/m2; 25-OH- D<25 ng/ml ; nutrition with calcium intake <800 mg per day, preeclampsia. Combination of these factors may increase the risk of osteopenia in the distal radius.

Osteoporosis and Bone Diseases. 2018;21(1):10-16
Case report
Long-term treatment options for postmenopausal osteoporosis: results of recent clinical studies of Denosumab
Belaya Z.E., Bilezikian J.P., Ershova O.B., Lesnyak O.M., Marchenkova L.A., Rodionova S.S., Rozhinskaya L.Y., Toroptsova N.V., Yureneva S.V.

Modern medications for osteoporosis (bisphosphonates, denosumab, teriparatide) are well-tolerated drugs, which can significantly lower vertebral and non-vertebral fracture risk according to prospective and observational studies in up to 10-year period. Certain drugs (denosumab, teriparatide) are active only during the treatment period and do not prevent bone loss and fracture risk after discontinuation, while such protective effect is observed in bisphosphonates. Despite impressive success of continuous 10-year denosumab treatament of severe osteoporosis, some of the recently published data suggest that vertebral fracture incidence is increased after treatment discontinuation, along with multiple vertebral fracture incidence, especially in patients with previous fractures.  Issues of osteoporosis treatment duration, sequential use of osteoporosis drugs and criteria for treatment discontinuation are now in focus of attention. European Medicines Agency (EMA) and European Calcified Tissue Society (ECTS) considered these issues in 2017. ЕМА considered fractures after denosumab discontinuation as a natural disease course and did not recommend any changes in product instruction. The main conclusion of ECTS is that the possibility of multiple fractures development after denosumab discontinuation exists, however, there is still not enough firm evidence, as well as effective countermeasures. Clinicians and patients should be aware of potential risk. Both EMA and ECTS suggest considering denosumab treatment or discontinuation after 5-year treatment period or possibly replacing with bisphosphonates. Recent data suggest that prolonged osteoporosis treatment can be done in accordance with the concept of treatment until target goal (for example, achievement of femoral T-score -2.0SD and higher).  In our review, we focus on recent data concerning the issues stated above. This topic was also discussed on Russian Osteoporosis Association (ROA) expert meeting in Saint Petersburg on 24 may 2018, chaired by ROA president, professor Olga Lesnyak and Columbia University professor, J.P. Bilezikian. As a result, an Expert Council resolution was written and introduced in the article.

Osteoporosis and Bone Diseases. 2018;21(1):17-22
Osteogenesis imperfecta as a cause of death
Malygina A.A., Grebennikova T.A., Tiulpakov A.N., Belaya Z.E.

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.

Osteoporosis and Bone Diseases. 2018;21(1):23-27
Rare genetic diseases of the bone tissue: the case of a family with osteogenesis imperfecta and X-linked hypophosphataemia
Popova I.Y., Grebennikova T.A., Tiulpakov A.N., Kulikova K.S., Rozhinskaya L.Y., Belaya Z.E.

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 clinician’s and the patient’s perspective.

Osteoporosis and Bone Diseases. 2018;21(1):28-33

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