Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe — recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency

Wstęp: Wyniki badań z ostatnich lat dokumentują wiele korzyści wynikających z działania witaminy D na organizm człowieka na wszystkichetapach jego życia. Większość badań epidemiologicznych sugeruje, że niedobór witaminy D jest powszechny wśród mieszkańców EuropyŚrodkowej. Naturalną konsekwencją tej sytuacji jest konieczność ciągłego uświadamiania społeczeństwu oraz środowisku medycznemu,jaką rolę odgrywa witamina D w rozwoju i funkcjonowaniu organizmu ludzkiego.Metody: Na podstawie przeglądu danych literaturowych Polski Zespół Wielodyscyplinarny opracował tezy dotyczące zasad suplementacjiwitaminą D, które przesłano do członków Komitetu Naukowego konferencji „Witamina D — minimum, maksimum, optimum”,19–20 Październik, 2012, Warszawa. W trakcie powyższej konferencji z udziałem 550 delegatów oraz Ekspertów różnych dziedzin medycynyomówiono i przedyskutowano propozycje wytycznych suplementacji witaminą D populacji Europy Środkowej.Wyniki: W efekcie przeprowadzonych dyskusji Zespół Ekspertów opracował wytyczne suplementacji witaminą D dla wszystkich grupwiekowych populacji Europy Środkowej. Określono również kryteria diagnostyczne charakteryzujące stan zaopatrzenia organizmu w witaminę D: deficyt witaminy D ustalono jako stężenie 25(OH)D < 20 ng/mL (< 50 nmol/L)], suboptymalne zaopatrzenie jako stężenie25(OH)D wynoszące 20–30 ng/mL (50–75 nmol/L), a stężenie 30–50 ng/mL (75–125 nmol/L) uznano za docelowe dla zapewnienia efektuplejotropowego witaminy D.Wnioski: Poprawa obecnego stanu zaopatrzenia witaminy D w grupach dzieci, młodzieży, osób aktywnych zawodowo i seniorówpowinna zostać włączona do priorytetów polityki zdrowotnej społeczeństw Europy Środkowej.Introduction: Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium–phosphate metabolismas well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activityappear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest thatVitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conferencefocused on overcoming Vitamin D deficiency.Methods: After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses onrecommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to ScientificCommittee members of the ‘Vitamin D — minimum, maximum, optimum’ conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting ‘Vitamin D — minimum, maximum, optimum’ was held on October 19–20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists’ votingwere reviewed and discussed during eight plenary sessions and two workshops.Results: Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges ofserum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20–30 ng/mL(50–75 nmol/L)], and target concentration for optimal Vitamin D effects [30–50 ng/mL (75–125 nmol/L)]. General practical guidelines regardingsupplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, childrenand adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed.Conclusions: Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementationguidance and population strategies for Vitamin D in Central Europe

Association of Vitamin D Receptor Gene Variation With Osteoporosis Risk in Belarusian and Lithuanian Postmenopausal Women

Vitamin D receptor (VDR) is one of the main mediators of vitamin D biological activity. VDR dysfunction might substantially contribute to development of postmenopausal osteoporosis (PMO). Numerous studies have revealed the effects of several VDR gene variants on osteoporosis risk, although significant variation in different ethnicities have been suggested. The main purpose of this work was to assess the frequency of distribution of VDR genetic variants with established effect and evaluate their haplotype association with the risk of PMO in a cohort of Belarusian and Lithuanian women. Case group included women with PMO (n = 149), the control group comprised women with normal bone mineral density (BMD) and without previous fragility fractures (n = 172). Both groups were matched for age, height, sex, and BMI—no statistically significant differences observed. VDR gene polymorphic variants (ApaI rs7975232, BsmI rs1544410, TaqI rs731236, and Cdx2 rs11568820) were determined using polymerase chain reaction and restriction fragment length polymorphism. The lumbar spine (L1-L4) and femoral neck BMD was measured using dual-energy X-ray absorptiometry. Association between each VDR variant and PMO risk was assessed using multiple logistic regression. The genotyping revealed statistically significant difference in the rs7975232 genotype frequencies between the patients and the controls (homozygous C/C genotype was overrepresented in patients, p = 0.008). Patients with osteoporosis were also three times more likely to carry the rs1544410 G/G genotype, when compared to controls. We found that rs7975232, rs1544410, and rs731236 variants were in a strong direct linkage disequilibrium (p < 0.0001), suggesting that risk alleles of these markers are preferably inherited jointly. For the bearers of C-G-C haplotype (consisting of rs7975232, rs1544410, and rs731236 unfavorable alleles), the risk of PMO was significantly higher (OR = 4.7, 95% CI 2.8–8.1, p < 0.0001) compared to controls. This haplotype was significantly over-represented in PMO group compared to all other haplotypes. Our findings highlight the importance of identified haplotypes of VDR gene variants. Complex screening of these genetic markers can be used to implement personalized clinical approach for prevention, treatment, and rehabilitation programs

FRAX-based intervention thresholds in eight Eurasian countries: Armenia, Belarus, Georgia, Kazakhstan, the Kyrgyz Republic, Moldova, the Russian Federation, and Uzbekistan

Summary: age-specific intervention and assessment thresholds based on FRAX® were developed for eight Eurasian countries participating in the EVA study (Armenia, Belarus, Georgia, Moldova, Kazakhstan, the Kyrgyz Republic, the Russian Federation, and Uzbekistan). The intervention thresholds (major osteoporotic fracture) ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for people at age 50 years, and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. These thresholds enable a substantial advance in the ease of detection of individuals at high fracture risk.Introduction: the purpose of this study was to derive and compare FRAX-based intervention and BMD assessment thresholds for 8 Eurasian countries in the EVA study.Methods: the intervention threshold (IT) was set at a 10-year probability of a major osteoporotic fracture (MOF), calculated without BMD, equivalent to a woman with a prior fragility fracture but no other clinical risk factors, and a body mass index (BMI) of 25.0 kg/m2. The lower assessment threshold was set at a 10-year probability of a MOF in women with BMI of 25.0 kg/m2, without previous fracture or other clinical risk factors. The upper assessment threshold was set at 1.2 times the IT.Results: the age-specific intervention thresholds ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for men and women at the age of 50 years and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. The difference between countries was most evident at younger ages and become progressively less with advancing age.Conclusions: for the 8 Eurasian countries, the newly established FRAX-based intervention thresholds provide an opportunity to improve the clinical detection of both men and women with a high risk of fracture and improve treatment rates

Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis

Introduction Long-term treatment is used in patients with osteoporosis, and bisphosphonates (BPs) are the most commonly prescribed medications. However, in some patients this therapy is not effective, cause different side effects and complications. Unfortunately, at least one year is needed to identify and confirm an ineffectiveness of BPs therapy on bone mineral density (BMD). Among other factors, a response to BPs therapy may also be explained by genetic factors. The aim of this study was to analyze the influence of SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 gene variants on the response to treatment with aminobisphosphonates. Materials and methods Women with postmenopausal osteoporosis were included to this study if they used aminobisphosphonates for at least 12 months. Exclusion criteria were: persistence on BPs therapy less than 80%, bone metabolic diseases, diseases deemed to affect bone metabolism, malignant tumors, using of any medications influencing BMD. The study protocol was approved by the local ethics committee. The BMD at the lumbar spine and femoral neck were measured using dual x-ray absorptiometry (GE Lunar) before and at least 12 months after treatment with BPs. According to BMD change, patients were divided in two groups–responders and nonresponders to BPs terapy. Polymorphic variants in SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 genes were determined using PCR analysis with TaqMan probes (Thermo Scientific). Results In total, 201 women with BPs therapy were included in the study. No statistically significant differences were observed in age, age at menopause, weight, height, BMI and baseline BMD levels between responders (122 subjects) and non-responders (79 subjects). As single markers, the SOST rs1234612 T/T (OR = 2.3; P = 0.02), PTH rs7125774 T/T (OR = 2.8, P = 0.0009), FDPS rs2297480 G/G (OR = 29.3, P = 2.2×10 ), and GGPS1 rs10925503 C/C+C/T (OR = 2.9; P = 0.003) gene variants were over-represented in nonresponders group. No significant association between FGF2 rs6854081 and LRP5 rs3736228 gene variants and response to BPs treatment was observed. The carriers of T-T-G-C allelic combination (constructed from rs1234612, rs7125774, rs2297480, and rs10925503) were predisposed to negative response to BPs treatment (OR = 4.9, 95% CI 1.7–14.6, P = 0.005). The C-C-T-C combination was significantly over-represented in responders (OR = 0.1, 95% CI 0.1–0.5, P = 0.006). Conclusions Our findings highlight the importance of identified single gene variants and their allelic combinations for pharmacogenetics of BPs therapy of osteoporosis. Complex screening of these genetic markers could be used as a new strategy for personalized antiresorptive therapy

FRAX-based intervention thresholds in eight Eurasian countries : Armenia, Belarus, Georgia, Kazakhstan, the Kygyz Republic, Moldova, the Russian Federation, and Uzbekistan

Summary Age-specific intervention and assessment thresholds based on FRAX® were developed for eight Eurasian countries participating in the EVA study (Armenia, Belarus, Georgia, Moldova, Kazakhstan, the Kyrgyz Republic, the Russian Federation, and Uzbekistan). The intervention thresholds (major osteoporotic fracture) ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for people at age 50 years, and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. These thresholds enable a substantial advance in the ease of detection of individuals at high fracture risk. Introduction The purpose of this study was to derive and compare FRAX-based intervention and BMD assessment thresholds for 8 Eurasian countries in the EVA study. Methods The intervention threshold (IT) was set at a 10-year probability of a major osteoporotic fracture (MOF), calculated without BMD, equivalent to a woman with a prior fragility fracture but no other clinical risk factors, and a body mass index (BMI) of 25.0 kg/m2. The lower assessment threshold was set at a 10-year probability of a MOF in women with BMI of 25.0 kg/m2, without previous fracture or other clinical risk factors. The upper assessment threshold was set at 1.2 times the IT. Results The age-specific intervention thresholds ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for men and women at the age of 50 years and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. The difference between countries was most evident at younger ages and become progressively less with advancing age. Conclusions For the 8 Eurasian countries, the newly established FRAX-based intervention thresholds provide an opportunity to improve the clinical detection of both men and women with a high risk of fracture and improve treatment rates