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Маркеры и генетические предикторы остеопороза в рутинной клинической практике
Гребенникова Т.А., Трошина В.В., Белая Ж.Е. Маркеры и генетические предикторы остеопороза в рутинной клинической практике. Consilium Medicum. 2019; 21 (4): 97–102. DOI: 10.26442/20751753.2019.4.190323
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Grebennikova T.A., Troshina V.V., Belaia Zh.E. Markers and genetic predictors of osteoporosis in routine clinical practice. Consilium Medicum. 2019; 21 (4): 97–102. DOI: 10.26442/20751753.2019.4.190323
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Аннотация
Целью обзора является освещение основных показателей фосфорно-кальциевого обмена, маркеров остеопороза, генетических предикторов заболевания и их значимости в практике клинициста. Остеопороз является распространенной проблемой общественного здравоохранения, которая нередко недооценивается. Заболевание часто диагностируется ретроспективно после развития низкотравматичного перелома. До 25% низкотравматичных переломов обусловлены вторичным остеопорозом или другими причинами нарушений фосфорно-кальциевого обмена. Для дифференциальной диагностики остеопороза необходимо исследование основных показателей фосфорно-кальциевого обмена: фосфора и кальция. Маркеры костного ремоделирования: костно-специфическая щелочная фосфатаза, остеокальцин, N-концевой пропептид проколлагена 1-го типа, С-концевой телопептид коллагена 1-го типа, имеют значение для динамической оценки эффективности лечения остеопороза и должны использоваться более широко. Использование анализа полиморфизма генов COL1A1, CALCR, VDR для изучения предрасположенности к развитию остеопороза остается обсуждаемым вопросом и требует дальнейшего исследования. Для написания данного обзора нами проанализирована отечественная и зарубежная литература, преимущественно опубликованная в последние 5 лет и посвященная проблеме остеопороза. На основании изученных материалов сформировано глубокое понимание специфики использования показателей фосфорно-кальциевого обмена, маркеров остеопороза и встречающегося полиморфизма генов в рутинной клинической практике. Таким образом, характер изложенного материала носит практический характер для клинициста.
Ключевые слова: остеокальцин, щелочная фосфатаза, P1NP, COL1A1, CALCR, фосфор, кальций.
Ключевые слова: остеокальцин, щелочная фосфатаза, P1NP, COL1A1, CALCR, фосфор, кальций.
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The review aimed to provide information on main characteristics of calcium and phosphate metabolism, osteoporosis markers, genetic predictors of the disorder and their significance in clinical practice. Osteoporosis is a common problem of public healthcare that is often underestimated. The disorder is often diagnosed retrospectively after a fragility fracture. About 25% of fragility fractures are associated with secondary osteoporosis or with other causes of calcium and phosphorus metabolism disorders. Estimation of main indicators of calcium and phosphate metabolism: calcium and phosphorus is necessary for osteoporosis differential diagnosis. Markers of bone remodeling such as bone-specific alkaline phosphatase, osteocalcin, N-terminal propeptide of type 1 procollagen, and C-terminal telopeptide of type 1 collagen are important in dynamics assessment of osteoporosis treatment effectiveness and should be used more widely. The use of COL1A1, CALCR, VDR genes polymorphisms analysis for assessment of susceptibility to osteoporosis development is a question under consideration and requires further investigations. In order to write this review we analyzed Russian and foreign literature mostly published in the last 5 years and dedicated to the problem of osteoporosis. On the basis of literature study a deep understanding of specificities of the use of calcium and phosphate metabolism characteristics, osteoporosis markers and gene polymorphism in routine clinical practice was formed. Therefore, the presented material is quite practical for clinical physicians.
Key words: osteocalcin, alkaline phosphatase, P1NP, COL1A1, CALCR, phosphorus, calcium.
Key words: osteocalcin, alkaline phosphatase, P1NP, COL1A1, CALCR, phosphorus, calcium.
Полный текст
Список литературы
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[Mel'nichenko G.A., Belaia Zh.E., Rozhinskaia L.Ia. et al. Federal'nye klinicheskie rekomendatsii po diagnostike, lecheniiu i profilaktike osteoporoza. Problemy endokrinologii. 2017; 63 (6): 392–426 (in Russian).]
2. Zagzag J, Hu MI, Fisher SB, Perrier ND. Hypercalcemia and cancer: Differential diagnosis and treatment. CA Cancer J Clin 2018; 68 (5): 377–86. DOI: 10.3322/caac.21489
3. Попова И.Ю., Гребенникова Т.А., Тюльпаков А.Н. и др. Редкие заболевания костной ткани: клиническое наблюдение семьи с несовершенным остеогенезом и фосфопенической формой остемаляции. Остеопороз и остеопатии. 2018; 21 (1): 28–33.
[Popova I.Iu., Grebennikova T.A., Tiul'pakov A.N. et al. Redkie zabolevaniia kostnoi tkani: klinicheskoe nabliudenie sem'i s nesovershennym osteogenezom i fosfopenicheskoi formoi ostemaliatsii. Osteoporoz i osteopatii. 2018; 21 (1): 28–33 (in Russian).]
4. Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer 2011; 18 (3): R53–77. DOI: 10.1530/ERC-11-0006
5. Hlaing TT, Compston JE. Biochemical markers of bone turnover – uses and limitations. Ann Clin Biochem 2014; 51 (Pt 2): 189–202. DOI: 10.1177/0004563213515190
6. Whyte MP. Hypophosphatasia – aetiology, nosology, pathogenesis, diagnosis and treatment. Nature Reviews Endocrinology 2016; 12 (4): 233–46. DOI: 10.1038/nrendo.2016.14
7. Wheater G, Elshahaly M, Tuck S et al. The clinical utility of bone marker measurements in osteoporosis. J Translat Med 2013; 11: 201.
8. Ларина В.Н., Михайлусова В.П., Распопова Т.Н. Применение биохимических маркеров костного обмена в повседневной деятельности врача. Лечебное дело. 2015; 2: 10–4.
[Larina V.N., Mikhailusova V.P., Raspopova T.N. Primenenie biokhimicheskikh markerov kostnogo obmena v povsednevnoi deiatel'nosti vracha. Lechebnoe delo. 2015; 2: 10–4 (in Russian).]
9. Rathore B, Manisha S, Vishnu K, Aparna M. Osteocalcin: an emerging biomarker for bone turnover. Int J Res Med Sci 2016; 4 (9): 3670–4. doi.org/10.18203/2320-6012.ijrms20162899
10. Панкратова Ю.В., Пигарова Е.А., Дзеранова Л.К. Витамин К-зависимые белки: остеокальцин, матриксный Gla-белок и их внекостные эффекты. Ожирение и метаболизм. 2013; 2: 11–4.
[Pankratova Iu.V., Pigarova E.A., Dzeranova L.K. Vitamin K-zavisimye belki: osteokal'tsin, matriksnyi Gla-belok i ikh vnekostnye effekty. Ozhirenie i metabolizm. 2013; 2: 11–4 (in Russian).]
11. Ivaska KK. Urinary Osteocalcin as a Marker of Bone Metabolism. Clin Chem 2005; 51 (3): 618–8. DOI: 10.1373/clinchem.2004.043901
12. Jagtap VR, Ganu JV, Nagane NS. BMD and Serum Intact Osteocalcin in Postmenopausal Osteoporosis Women. Ind J Clin Biochem 2010; 26 (1): 70–3. DOI: 10.1007/s12291-010-0074-2
13. Белая Ж.Е., Рожинская Л.Я., Мельниченко Г.А. и др. Возможности маркера костного обмена – остеокальцина – для диагностики эндогенного гиперкортицизма и вторичного остеопороза. Остеопороз и остеопатии. 2011; 2: 7–10.
[Belaia Zh.E., Rozhinskaia L.Ia., Mel'nichenko G.A. i dr. Vozmozhnosti markera kostnogo obmena – osteokal'tsina – dlia diagnostiki endogennogo giperkortitsizma i vtorichnogo osteoporoza. Osteoporoz i osteopatii. 2011; 2: 7–10 (in Russian).]
14. Ayesha A, Vanitha GMN. Serum osteocalcin levels in metabolic syndrome. Int J Clin Biochem Res 2016; 3 (4): 453–60. DOI: 10.18231/2394-6377.2016.0024
15. Bilotta FL, Arcidiacono B, Messineo S et al. Insulin and osteocalcin: further evidence for a mutual cross-talk. Endocrine 2017; 59 (3): 622–32. DOI: 10.1007/s12020-017-1396-0
16. Reyes García R, Rozas Moreno P, Muñoz-Torres M. Osteocalcin and atherosclerosis: A complex relationship. Diabetes Res Clin Practice 2011; 92 (3); 405–6. DOI: 10.1016/j.diabres.2010.08.019
17. Moser SC, van der Eerden BCJ. Osteocalcin – A Versatile Bone-Derived Hormone. Front Endocrinol 2019; 9: 794. DOI: 10.3389/fendo.2018.00794
18. Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev 2005; 26: 97–122.
19. Koivula M-K, Ruotsalainen V, Bjorkman M et al. Difference between total and intact assays for N-terminal propeptide of type I procollagen reflects degradation of pN-collagen rather than denaturation of intact propeptide. Ann Clin Biochem 2010; 47: 67–71.
20. Brown JP, Albert C, Nassar BA et al. Bone turnover markers in the management of osteoporosis. Clin Biochem 2009; 42: 929–42.
21. Машейко И.В. Биохимические маркеры в оценке процессов ремоделирования костной ткани при остеопении и остеопорозе. Журн. Гродненского государственного медицинского университета. 2017; 2: 149–53.
[Masheiko I.V. Biokhimicheskie markery v otsenke protsessov remodelirovaniia kostnoi tkani pri osteopenii i osteoporoze. Zhurn. Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2017; 2: 149–53 (in Russian).]
22. Iftikhar A, Tousif S. Ahmed, Asim T. Review of Bone Turn over Biomarkers for Early Diagnose of Osteoporosis. JAMMR 2018; 26 (8): 1–8.
23. Greenblatt M, Tsai J, Wein M. Bone turnover markers in the diagnosis and monitoring of metabolic bone disease. Clin Chem 2016; 63: 464–74.
24. Vasikaran S, Cooper C, Eastell R et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine Position on bone marker standards in osteoporosis. Clin Chem Lab Med 2011; 49: 1271–4.
25. Arslan M, Cogendez E, Eken M et al. Serum beta crosslaps as a predictor for osteoporosis in postmenopausal women. Istanbul Tıp Fakultesi Dergisi Cilt 2015; 78 (2): 36–40. DOI: 10.18017/iuitfd.m.13056441.2015.78/2.36-40
26. Riera-Espinoza GS, Cordero Y, Mendoza S et al. Early P1NP Suppression during Treatment of Low Bone Mass Postmenopausal Women with Risedronate 150 mg once-a Month. Ortho Rheum Open Access J 2017; 8 (2): 555732. DOI: 10.19080/OROAJ.2017.08.555732
27. Dal Prá KJ, Lemos CAA, Okamoto R et al. Efficacy of the C-terminal telopeptide test in predicting the development of bisphosphonate-related osteonecrosis of the jaw: a systematic review. Int J Oral Maxillofacial Surg 2017; 46 (2): 151–6. DOI: 10.1016/j.ijom.2016.10.009
28. Wichers M, Schmidt E, Bidlingmaier F, Klingmuller D. Diurnal rhythm of crosslaps in human serum. Clin Chem 1999; 45:1858–60.
29. Delanaye P, Souberbielle J, Lafage-Proust M et al. Can we use circulating biomarkers to monitor bone turnover in CKD haemodialysis patients? Hypotheses and facts. Nephrol Dial Transplant 2013; 29: 997–1004.
30. Bardai G, Moffatt P, Glorieux FH, Rauch F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporosis Int 2016; 27 (12): 3607–13. DOI: 10.1007/s00198-016-3709-1
31. Малыгина А.А., Гребенникова Т.А., Тюльпаков А.Н., Белая Ж.Е. Несовершенный остеогенез как причина летального исхода. Остеопороз и остеопатии. 2018; 21 (1): 23–7.
[Malygina A.A., Grebennikova T.A., Tiul'pakov A.N., Belaia Zh.E. Nesovershennyi osteogenez kak prichina letal'nogo iskhoda. Osteoporoz i osteopatii. 2018; 21 (1): 23–7 (in Russian).]
32. Mann V, Ralston S. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 2003; 32 (6): 711–7. DOI: 10.1016/s8756-3282(03)00087-5
33. Mann V, Hobson EE, Li B et al. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107 (7): 899–907. DOI: 10.1172/JCI10347
34. Москаленко М.В., Асеев М.В., Котова С.М., Баранов В.С. Анализ ассоциации аллелей генов COLLAL, VDR и CALCR с развитием остеопороза. Экологическая генетика человека. 2004; 2 (1): 38–43.
[Moskalenko M.V., Aseev M.V., Kotova S.M., Baranov V.S. Analiz assotsiatsii allelei genov COLLAL, VDR i CALCR s razvitiem osteoporoza. Ekologicheskaia genetika cheloveka. 2004; 2 (1): 38–43 (in Russian).]
35. Huebner AK, Keller J, Catala-Lehnen P et al. The role of calcitonin and a-calcitonin gene-related peptide in bone formation. Arch Biochem Biophys 2008; 473 (2): 210–7. DOI: 10.1016/j.abb.2008.02.013
36. Wimalawansa S. Physiology of Calcitonin and Its Therapeutic Uses. Reference Module Biomed Sci 2018; 1: 178–91. DOI: 10.1016/B978-0-12-801238-3.95758-1
37. Russell FA, King R, Smillie S-J et al. Calcitonin Gene-Related Peptide: Physiology and Pathophysiology. Physiological Rev 2014; 94 (4): 1099–142. DOI: 10.1152/physrev.00034.2013
38. Chaiya I, Rattanakul C. An impulsive mathematical model of bone formation and resorption: effects of parathyroid hormone, calcitonin and impulsive estrogen supplement. Adv Difference Equations 2017; 2017 (1): 153. DOI: 10.1186/s13662-017-1206-2
39. Шилина Н.М., Сорокина Е.Ю., Иванушкина Т.А. и др. Изучение полиморфизма rs11801197 гена рецептора кальцитонина (CALCR) у женщин и детей Москвы с различным уровнем костной прочности. Вопр. питания. 2017; 86 (1): 28–34.
[Shilina N.M., Sorokina E.Iu., Ivanushkina T.A. et al. Izuchenie polimorfizma rs11801197 gena retseptora kal'tsitonina (CALCR) u zhenshchin i detei Moskvy s razlichnym urovnem kostnoi prochnosti. Vopr. pitaniia. 2017; 86 (1): 28–34 (in Russian).]
40. Zimmermann A, Popp RA, Rossmann H et al. Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1. Ther Clinical Risk Management 2018; 14: 2069–80. DOI: 10.2147/tcrm.s177480
41. Masi L, Becherini L, Gennari L et al. Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women. Biochem Biophys Res Commun 1998; 245 (2): 622–6.
42. Taboulet J, Frenkian M, Frendo JL et al. Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Hum Mol Genet 1998; 7 (13): 2129–33.
43. Мальцев А.В. Исследование генетических факторов развития постменопаузального остеопороза в Волго-Уральском регионе. Автореф. дис. … канд. биол. наук. Уфа, 2014.
[Mal'tsev A.V. Issledovanie geneticheskikh faktorov razvitiia postmenopauzal'nogo osteoporoza v Volgo-Ural'skom regione. Avtoref. dis. … kand. biol. nauk. Ufa, 2014 (in Russian).]
44. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266–81.
45. Qin G, Dong Z, Zeng P. Association of vitamin D receptor BsmI gene polymorphism with risk of osteoporosis: a meta-analysis of 41 studies. Mol Biol Rep 2013; 40: 497–506. https://doi.org/10.1007/s11033-012-2086-x
46. Chantarangsu S, Sura T, Mongkornkarn S et al. Vitamin D Receptor Gene Polymorphism and Smoking in the Risk of Chronic Periodontitis. J Periodontology 2016; 87: 1343–51. https://doi.org/10.1902/jop.2016.160222
47. Zhang L, Yin X, Wang J et al. Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis. Sci Rep 2018; 8 (1): 981. DOI: 10.1038/s41598-017-18670-7
48. Jin H, Evangelou E, Ioannidis JPA, Ralston SH. Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies. Osteoporosis Int 2010; 22 (3): 911–21. DOI: 10.1007/s00198-010-1364-5
49. Bustamante M, Nogués X, Enjuanes A et al. COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporosis Int 2006; 18 (2): 235–43. DOI: 10.1007/s00198-006-0225-8
50. Sowers M, Willing M, Burns T et al. Genetic Markers, Bone Mineral Density, and Serum Osteocalcin Levels. J Bone Min Res 1999; 14 (8): 1411–9. DOI: 10.1359/jbmr.1999.14.8.1411
________________________________________________
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17. Moser SC, van der Eerden BCJ. Osteocalcin – A Versatile Bone-Derived Hormone. Front Endocrinol 2019; 9: 794. DOI: 10.3389/fendo.2018.00794
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19. Koivula M-K, Ruotsalainen V, Bjorkman M et al. Difference between total and intact assays for N-terminal propeptide of type I procollagen reflects degradation of pN-collagen rather than denaturation of intact propeptide. Ann Clin Biochem 2010; 47: 67–71.
20. Brown JP, Albert C, Nassar BA et al. Bone turnover markers in the management of osteoporosis. Clin Biochem 2009; 42: 929–42.
21. Masheiko I.V. Biokhimicheskie markery v otsenke protsessov remodelirovaniia kostnoi tkani pri osteopenii i osteoporoze. Zhurn. Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2017; 2: 149–53 (in Russian).
22. Iftikhar A, Tousif S. Ahmed, Asim T. Review of Bone Turn over Biomarkers for Early Diagnose of Osteoporosis. JAMMR 2018; 26 (8): 1–8.
23. Greenblatt M, Tsai J, Wein M. Bone turnover markers in the diagnosis and monitoring of metabolic bone disease. Clin Chem 2016; 63: 464–74.
24. Vasikaran S, Cooper C, Eastell R et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine Position on bone marker standards in osteoporosis. Clin Chem Lab Med 2011; 49: 1271–4.
25. Arslan M, Cogendez E, Eken M et al. Serum beta crosslaps as a predictor for osteoporosis in postmenopausal women. Istanbul Tıp Fakultesi Dergisi Cilt 2015; 78 (2): 36–40. DOI: 10.18017/iuitfd.m.13056441.2015.78/2.36-40
26. Riera-Espinoza GS, Cordero Y, Mendoza S et al. Early P1NP Suppression during Treatment of Low Bone Mass Postmenopausal Women with Risedronate 150 mg once-a Month. Ortho Rheum Open Access J 2017; 8 (2): 555732. DOI: 10.19080/OROAJ.2017.08.555732
27. Dal Prá KJ, Lemos CAA, Okamoto R et al. Efficacy of the C-terminal telopeptide test in predicting the development of bisphosphonate-related osteonecrosis of the jaw: a systematic review. Int J Oral Maxillofacial Surg 2017; 46 (2): 151–6. DOI: 10.1016/j.ijom.2016.10.009
28. Wichers M, Schmidt E, Bidlingmaier F, Klingmuller D. Diurnal rhythm of crosslaps in human serum. Clin Chem 1999; 45:1858–60.
29. Delanaye P, Souberbielle J, Lafage-Proust M et al. Can we use circulating biomarkers to monitor bone turnover in CKD haemodialysis patients? Hypotheses and facts. Nephrol Dial Transplant 2013; 29: 997–1004.
30. Bardai G, Moffatt P, Glorieux FH, Rauch F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporosis Int 2016; 27 (12): 3607–13. DOI: 10.1007/s00198-016-3709-1
31. Malygina A.A., Grebennikova T.A., Tiul'pakov A.N., Belaia Zh.E. Nesovershennyi osteogenez kak prichina letal'nogo iskhoda. Osteoporoz i osteopatii. 2018; 21 (1): 23–7 (in Russian).
32. Mann V, Ralston S. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 2003; 32 (6): 711–7. DOI: 10.1016/s8756-3282(03)00087-5
33. Mann V, Hobson EE, Li B et al. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107 (7): 899–907. DOI: 10.1172/JCI10347
34. Moskalenko M.V., Aseev M.V., Kotova S.M., Baranov V.S. Analiz assotsiatsii allelei genov COLLAL, VDR i CALCR s razvitiem osteoporoza. Ekologicheskaia genetika cheloveka. 2004; 2 (1): 38–43 (in Russian).
35. Huebner AK, Keller J, Catala-Lehnen P et al. The role of calcitonin and a-calcitonin gene-related peptide in bone formation. Arch Biochem Biophys 2008; 473 (2): 210–7. DOI: 10.1016/j.abb.2008.02.013
36. Wimalawansa S. Physiology of Calcitonin and Its Therapeutic Uses. Reference Module Biomed Sci 2018; 1: 178–91. DOI: 10.1016/B978-0-12-801238-3.95758-1
37. Russell FA, King R, Smillie S-J et al. Calcitonin Gene-Related Peptide: Physiology and Pathophysiology. Physiological Rev 2014; 94 (4): 1099–142. DOI: 10.1152/physrev.00034.2013
38. Chaiya I, Rattanakul C. An impulsive mathematical model of bone formation and resorption: effects of parathyroid hormone, calcitonin and impulsive estrogen supplement. Adv Difference Equations 2017; 2017 (1): 153. DOI: 10.1186/s13662-017-1206-2
39. Shilina N.M., Sorokina E.Iu., Ivanushkina T.A. et al. Izuchenie polimorfizma rs11801197 gena retseptora kal'tsitonina (CALCR) u zhenshchin i detei Moskvy s razlichnym urovnem kostnoi prochnosti. Vopr. pitaniia. 2017; 86 (1): 28–34 (in Russian).
40. Zimmermann A, Popp RA, Rossmann H et al. Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1. Ther Clinical Risk Management 2018; 14: 2069–80. DOI: 10.2147/tcrm.s177480
41. Masi L, Becherini L, Gennari L et al. Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women. Biochem Biophys Res Commun 1998; 245 (2): 622–6.
42. Taboulet J, Frenkian M, Frendo JL et al. Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Hum Mol Genet 1998; 7 (13): 2129–33.
43. Mal'tsev A.V. Issledovanie geneticheskikh faktorov razvitiia postmenopauzal'nogo osteoporoza v Volgo-Ural'skom regione. Avtoref. dis. … kand. biol. nauk. Ufa, 2014 (in Russian).
44. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266–81.
45. Qin G, Dong Z, Zeng P. Association of vitamin D receptor BsmI gene polymorphism with risk of osteoporosis: a meta-analysis of 41 studies. Mol Biol Rep 2013; 40: 497–506. https://doi.org/10.1007/s11033-012-2086-x
46. Chantarangsu S, Sura T, Mongkornkarn S et al. Vitamin D Receptor Gene Polymorphism and Smoking in the Risk of Chronic Periodontitis. J Periodontology 2016; 87: 1343–51. https://doi.org/10.1902/jop.2016.160222
47. Zhang L, Yin X, Wang J et al. Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis. Sci Rep 2018; 8 (1): 981. DOI: 10.1038/s41598-017-18670-7
48. Jin H, Evangelou E, Ioannidis JPA, Ralston SH. Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies. Osteoporosis Int 2010; 22 (3): 911–21. DOI: 10.1007/s00198-010-1364-5
49. Bustamante M, Nogués X, Enjuanes A et al. COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporosis Int 2006; 18 (2): 235–43. DOI: 10.1007/s00198-006-0225-8
50. Sowers M, Willing M, Burns T et al. Genetic Markers, Bone Mineral Density, and Serum Osteocalcin Levels. J Bone Min Res 1999; 14 (8): 1411–9. DOI: 10.1359/jbmr.1999.14.8.1411
Авторы
Т.А.Гребенникова*, В.В.Трошина, Ж.Е.Белая
ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
*grebennikova@hotmail.com
ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
*grebennikova@hotmail.com
________________________________________________
Tatiana A. Grebennikova*, Viktoriia V. Troshina, Zhanna E. Belaia
Endocrinology Research Centre, Moscow, Russia
*grebennikova@hotmail.com
Endocrinology Research Centre, Moscow, Russia
*grebennikova@hotmail.com
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