porozendoОстеопороз и остеопатииOsteoporosis and Bone Diseases2072-26802311-0716Endocrinology Research Centre10.14341/osteo2013212-17porozendo-8853Research ArticleСтатьиArticlesГЕННО-ИНЖЕНЕРНЫЕ БИОЛОГИЧЕСКИЕ ПРЕПАРАТЫ В ТЕРАПИИ ОСТЕОПОРОЗА У БОЛЬНЫХРЕВМАТОИДНЫМ АРТРИТОМGENNO-INZhENERNYE BIOLOGIChESKIE PREPARATY V TERAPII OSTEOPOROZA U BOL'NYKhREVMATOIDNYM ARTRITOMДЫДЫКИНАИ СDYDYKINAI S

Кандидат медицинских наук, старший научный сотрудник лаборатории по изучению безопасности антиревматических препаратов

dydykina_is@mail.ruДЫДЫКИНАП СDYDYKINAP S

Аспирантка отдела метаболических заболеваний костей и суставов с Центром профилактики остеопороза (МЗ РФ)

-НАСОНОВЕ ЛNASONOVE L

Доктор медицинских наук, профессор, академик РАМН, директор

-ФГБУ «НИИР им. В.А.Насоновой» РАМН201315122013162№2 (2013)1217Copyright © ДЫДЫКИНА И.С., ДЫДЫКИНА П.С., НАСОНОВ Е.Л., 20132013ДЫДЫКИНА И.С., ДЫДЫКИНА П.С., НАСОНОВ Е.Л.DYDYKINA I.S., DYDYKINA P.S., NASONOV E.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.osteo-endojournals.ru/jour/article/view/8853

Представлены современные данные литературы о влиянии генно-инженерных биологических препаратов (ГИБП) на минеральную плотность кости, костный обмен и ремоделирование костной ткани. Благодаря высокой эффективности, эти препараты получили заслуженную популярность, несмотря на то, что применяются в ревматологии сравнительно недавно. Ведущую роль в патогенезе локальной и генерализованной резорбции кости, деструкции костной ткани при ревматоидном артрите играют медиаторы иммунного и воспалительного процессов (провоспалительные цитокины), к которым относят фактор некроза опухоли α, интерлейкины 1, 2,12,17, интерферон γ, а также простагландины, протеолитические ферменты (коллагеназа, другие протеазы) и др. описаны RANKL-зависимые и RANKL-независимые механизмы активации остеокластогенеза. В последние годы установлено, что ингибирование провоспалительных цитокинов не только уменьшает воспалительные изменения суставов, но и сдерживает развитие деструкции, препятствует развитию локального и генерализованного остеопороза. В настоящем обзоре обсуждаются результаты этих работ и поднимаются вопросы для будущих исследований.

The authors review the current literature data on the influence of the genetically engineered biological drugs on the bone mineral density, bone exchange and remodeling of bone are submitted. Due to high efficiency these drugs received the deserved popularity in spite of the fact that are applied in rheumatology rather recently. The leading role in pathogenesis of local and generalized bone resorption and destruction in rheumatoid arthritis is realized by mediators of immune and inflammatory processes (pro-inflammatory cytokinins): tumor necrosis factor a, interleukin 1, 2, 12, 17, interferon γ, and also prostaglandins, proteolytic enzymes (a collagenase, other proteases), etc. There are described RANKL — dependent and RANKL — independent mechanisms of activation the osteoclastogenesis. In recent years it is established that the inhibition of pro-inflammatory cytokinins not only reduces inflammatory changes of joints, but also constrains destruction development, interferes with development of bone erosions and generalized bone loss. In the present review results of these works are discussed and questions for future researches are brought up.

ревматоидный артритгенно-инженерные биологические препаратыпатогенез локальной и генерализованной резорбциифакторы риска вторичного остеопорозаминеральная плотность костипереломыrheumatoid arthritisgenetically engineered biological drugspathogenesis of local and generalized bone resorptionrisk factors of secondary osteoporosisbone mineral densitybone exchangeReferencesСигидин Я.А., Лукина Г.В. Ревматоидный артрит. М.: АНКО, 2001, 327с.Сигидин Я.А., Лукина Г.В. Ревматоидный артрит. М.: АНКО, 2001, 327с.Kanis J.A., Johanson H., Oden A., Johnell О., De Laet C., Melton III L.J., et al. A meta — analysis of prior corticosteroid use and fracture risk. J Bone Miner Res. 2000; 19: 893-899.Kanis J.A., Johanson H., Oden A., Johnell О., De Laet C., Melton III L.J., et al. A meta — analysis of prior corticosteroid use and fracture risk. J Bone Miner Res. 2000; 19: 893-899.Клинические рекомендации. Остеопороз. Диагностика, профилактика и лечение. Под ред. Л.И. Беневоленской, О.М. Лесняк.-М.: ГЕОТАР-Медиа, 2009;176с.Клинические рекомендации. Остеопороз. Диагностика, профилактика и лечение. Под ред. Л.И. Беневоленской, О.М. Лесняк.-М.: ГЕОТАР-Медиа, 2009;176с.Клинические рекомендации. Ревматология.2-е издание, исправленное, дополненное. Под ред. Акад. РАМН Е.Л.Насонова -М.: ГЕОТАР-Медиа, 2010;738с.Клинические рекомендации. Ревматология.2-е издание, исправленное, дополненное. Под ред. Акад. РАМН Е.Л.Насонова -М.: ГЕОТАР-Медиа, 2010;738с.Oezner P., Franke S., Muller A., et al. Relationship between soluble markers of immune activation and bone turnover in post-menopausal women with rheumatoid arthritis. J.Rheumatol.1999;38: 841—847.Oezner P., Franke S., Muller A., et al. Relationship between soluble markers of immune activation and bone turnover in post-menopausal women with rheumatoid arthritis. J.Rheumatol.1999;38: 841—847.Насонов Е.Л., Самсонов М.Ю. Новые направления исследования воспаления при ревматических заболеваниях. В кн. Избранные лекции по клинической ревматологии. Под ред. В.А. Насоновой и Н.В. Бунчука.-М.: «Медицина», 2001. — 270с.Насонов Е.Л., Самсонов М.Ю. Новые направления исследования воспаления при ревматических заболеваниях. В кн. Избранные лекции по клинической ревматологии. Под ред. В.А. Насоновой и Н.В. Бунчука.-М.: «Медицина», 2001. — 270с.Насонов Е.Л. Остеопороз при ревматических заболеваниях. В кн. Руководство по остеопорозу. Под ред. Л.И. Беноволенской.-М.: БИНОМ. Лаборатория знаний, 2003. — 524с.Насонов Е.Л. Остеопороз при ревматических заболеваниях. В кн. Руководство по остеопорозу. Под ред. Л.И. Беноволенской.-М.: БИНОМ. Лаборатория знаний, 2003. — 524с.Jimi E., Nakamura I., Duong L.T., et al. Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence osteoblasts/stromal cells. Exp. Cell Res., 1999; 247: 84—93.Jimi E., Nakamura I., Duong L.T., et al. Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence osteoblasts/stromal cells. Exp. Cell Res., 1999; 247: 84—93.Kobayashi K., Takahashi N., Jimi E., et al. Tumor necrosis factor-a stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J. Exp. Med., 2000; 191: 275—286.Kobayashi K., Takahashi N., Jimi E., et al. Tumor necrosis factor-a stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J. Exp. Med., 2000; 191: 275—286.Suda T., Takahashi N., Udagawa N., et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr. Rev., 1999; 20: 345—357.Suda T., Takahashi N., Udagawa N., et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr. Rev., 1999; 20: 345—357.C. J. Edwards & E. Williams. The role of interleukin-6 in rheumatoid arthritis-associated osteoporosis. Osteoporos Int 2010; 21:1287—1293.C. J. Edwards & E. Williams. The role of interleukin-6 in rheumatoid arthritis-associated osteoporosis. Osteoporos Int 2010; 21:1287—1293.Roland Axmann, Christina Bo'hm, Gerhard Kro'nke, Jochen Zwerina, Josef Smolen, Georg Schett. Inhibition of Interleukin-6 Receptor Directly Blocks Osteoclast Formation In Vitro and In Vivo Arthrits & Rheumatism Vol. 60, No. 9, September 2009; 2747—2756.Roland Axmann, Christina Bo'hm, Gerhard Kro'nke, Jochen Zwerina, Josef Smolen, Georg Schett. Inhibition of Interleukin-6 Receptor Directly Blocks Osteoclast Formation In Vitro and In Vivo Arthrits & Rheumatism Vol. 60, No. 9, September 2009; 2747—2756.Gravallese EM, Manning C, Tsay A, et al. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum. 2000; 43: 250—258.Gravallese EM, Manning C, Tsay A, et al. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum. 2000; 43: 250—258.Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature, 1999; 397: 315—323.Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature, 1999; 397: 315—323.Pettit AR, Ji H, von Stechow D, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol. 2001; 159: 1689—1699.Pettit AR, Ji H, von Stechow D, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol. 2001; 159: 1689—1699.Roux S, Orcel P. Bone loss. Factors that regulate osteoclast differentiation: an update. Arthritis Res., 2000; 2: 451—456.Roux S, Orcel P. Bone loss. Factors that regulate osteoclast differentiation: an update. Arthritis Res., 2000; 2: 451—456.Takayanagi H, Ogasawara K, Hida S, et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 2000; 408: 600—605.Takayanagi H, Ogasawara K, Hida S, et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 2000; 408: 600—605.Juji T, Hertz M, Aoki K, Horie D, et al. A novel therapeutic vaccine approach, targeting RANKL, prevents bone destruction in bone-related disorders. J. Bone Miner Metab. 2002; 20: 266—268.Juji T, Hertz M, Aoki K, Horie D, et al. A novel therapeutic vaccine approach, targeting RANKL, prevents bone destruction in bone-related disorders. J. Bone Miner Metab. 2002; 20: 266—268.Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994 Jul 2;344(8914):23—7.Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994 Jul 2;344(8914):23—7.Changhai Ding, Venkat Parameswaran, Ray Udayan, John Burgess, and Graeme Jones. Circulating Levels of Inflammatory Markers Predict Change in Bone Mineral Density and Resorption in Older Adults: A Longitudinal Study. J Clin Endocrinol Metab. 2008; 93: 1952—1958.Changhai Ding, Venkat Parameswaran, Ray Udayan, John Burgess, and Graeme Jones. Circulating Levels of Inflammatory Markers Predict Change in Bone Mineral Density and Resorption in Older Adults: A Longitudinal Study. J Clin Endocrinol Metab. 2008; 93: 1952—1958.Laan RF., Buijs WC., Verbeek AL., Draad MP., Corstens FH., van de Putte LB., van Riel PL. Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis. 1993 Jan;52(1):21—6.Laan RF., Buijs WC., Verbeek AL., Draad MP., Corstens FH., van de Putte LB., van Riel PL. Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis. 1993 Jan;52(1):21—6.Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994 Jul 2;344(8914):23—7.Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994 Jul 2;344(8914):23—7.Iwamoto J, Takeda T, Ichimura S Urinary cross-linked N-telopeptides of type I collagen levels in patients with rheumatoid arthritis. Calcif Tissue Int. 2003; 72:491—497.Iwamoto J, Takeda T, Ichimura S Urinary cross-linked N-telopeptides of type I collagen levels in patients with rheumatoid arthritis. Calcif Tissue Int. 2003; 72:491—497.Garnero P, Jouvenne P, Buchs N, Delmas PD, Miossec P. Uncoupling of bone metabolism in rheumatoid arthritis patients with or without joint destruction: assessment with serum type I collagen breakdown products. Bone 1999;24:381—385.Garnero P, Jouvenne P, Buchs N, Delmas PD, Miossec P. Uncoupling of bone metabolism in rheumatoid arthritis patients with or without joint destruction: assessment with serum type I collagen breakdown products. Bone 1999;24:381—385.van Tuyl LH, Voskuyl AE, Boers M, Geusens P, Landewe RB, Dijkmans BA, Lems WF. Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis. Ann Rheum Dis 2010; 69(9):1623—1628.van Tuyl LH, Voskuyl AE, Boers M, Geusens P, Landewe RB, Dijkmans BA, Lems WF. Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis. Ann Rheum Dis 2010; 69(9):1623—1628.Власова И.С., Гукасян Д.А., Смирнов А.В., Насонов Е.Л. Особенности генерализованного остеопороза у больных ревматоидным артритом. Остеопороз и остеопатии 1999; 3: 14—7.Власова И.С., Гукасян Д.А., Смирнов А.В., Насонов Е.Л. Особенности генерализованного остеопороза у больных ревматоидным артритом. Остеопороз и остеопатии 1999; 3: 14—7.Oelzner P, Schwabe A, Lehmann G, Eidner T, Franke S, Wolf G, Hein G. Significance of risk factors for osteoporosis is dependent on gender and menopause in rheumatoid arthritis. Rheumatol Int. 2008 Sep;28(11):1143-50. Epub 2008 Apr 30.Oelzner P, Schwabe A, Lehmann G, Eidner T, Franke S, Wolf G, Hein G. Significance of risk factors for osteoporosis is dependent on gender and menopause in rheumatoid arthritis. Rheumatol Int. 2008 Sep;28(11):1143-50. Epub 2008 Apr 30.Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register.Arthritis Rheum. 2000 Mar;43(3):522—30.Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register.Arthritis Rheum. 2000 Mar;43(3):522—30.rstavik RE, Haugeberg G, Mowinckel P, H0iseth A, Uhlig T, Falch JA, Halse JI, McCloskey E, Kvien TK. Vertebral deformities in rheumatoid arthritis: a comparison with population-based controls. Arch Intern Med. 2004 Feb 23;164(4):420—5.rstavik RE, Haugeberg G, Mowinckel P, H0iseth A, Uhlig T, Falch JA, Halse JI, McCloskey E, Kvien TK. Vertebral deformities in rheumatoid arthritis: a comparison with population-based controls. Arch Intern Med. 2004 Feb 23;164(4):420—5.Смирнов А.В., Насонова В.А. Минеральная плотность костной ткани по данным денситометрического исследования у больных ревматоидным артритом. Тезисы. Всероссийская конференция с международным участием «Медико-социальные проблемы костномышечных заболеваний в ХХ1 веке» Москва,2000; 93.Смирнов А.В., Насонова В.А. Минеральная плотность костной ткани по данным денситометрического исследования у больных ревматоидным артритом. Тезисы. Всероссийская конференция с международным участием «Медико-социальные проблемы костномышечных заболеваний в ХХ1 веке» Москва,2000; 93.Als O.S., Gotfredson A., Christiansen C. The effects of glucocorticoids on bone mass in rheumatoid arthritis patients: influence of menopausal state. Arthritis Rheum 1985; 28: 369—75.Als O.S., Gotfredson A., Christiansen C. The effects of glucocorticoids on bone mass in rheumatoid arthritis patients: influence of menopausal state. Arthritis Rheum 1985; 28: 369—75.Martin J.C., Munro R., Campbell M.K. et al. Effects of disease and corticosteroids on appendicular bone mass in postmenopausal women with rheumatoid arthritis: comparison with axial measurements. Br J Rheumatol 1997; 36: 43—9.Martin J.C., Munro R., Campbell M.K. et al. Effects of disease and corticosteroids on appendicular bone mass in postmenopausal women with rheumatoid arthritis: comparison with axial measurements. Br J Rheumatol 1997; 36: 43—9.Peel N.F., Moore D.J., Barrington N.A. et al. Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 1995; 54: 801—6.Peel N.F., Moore D.J., Barrington N.A. et al. Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 1995; 54: 801—6.Sambrook PN., Eisman J.A., Yeates M.G. et al. Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids. Ann Rheum Dis 1986; 45: 950—3.Sambrook PN., Eisman J.A., Yeates M.G. et al. Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids. Ann Rheum Dis 1986; 45: 950—3.Sambrook PN., Eisman J.A., Champion G.D. et al. Determinants of axial bone loss in rheumatoid arthritis. Arthritis Rheum 1987; 30: 721—8.Sambrook PN., Eisman J.A., Champion G.D. et al. Determinants of axial bone loss in rheumatoid arthritis. Arthritis Rheum 1987; 30: 721—8.Федина Т.П., Братыгина Е.А., Старкова А.С., Петрова Е.В., Дыдыкина П.С., Арбиева В.К., Мукагова М.В., Смирнов А.В., Алексеева Л.И., Дыдыкина И.С., Насонов Е.Л. Денситометрическая оценка костной ткани больных ревматоидным артритом. Тезисы I1 Всероссийского конгресса ревматологов России. г.Ярославль 26-29 апреля 2011; (314), с.81.Федина Т.П., Братыгина Е.А., Старкова А.С., Петрова Е.В., Дыдыкина П.С., Арбиева В.К., Мукагова М.В., Смирнов А.В., Алексеева Л.И., Дыдыкина И.С., Насонов Е.Л. Денситометрическая оценка костной ткани больных ревматоидным артритом. Тезисы I1 Всероссийского конгресса ревматологов России. г.Ярославль 26-29 апреля 2011; (314), с.81.Насонов Е.Л., Скрипникова И.А., Насонова В.А. Проблема остеопороза в ревматологии.- М.: «СТИН», 1997;329 с.Насонов Е.Л., Скрипникова И.А., Насонова В.А. Проблема остеопороза в ревматологии.- М.: «СТИН», 1997;329 с.Oezner P., Franke S., Muller A., et al. Relationship between soluble markers of immune activation and bone turnover in postmenopausal women with rheumatoid arthritis. J.Rheumatol.1999; 38: 841—847.Oezner P., Franke S., Muller A., et al. Relationship between soluble markers of immune activation and bone turnover in postmenopausal women with rheumatoid arthritis. J.Rheumatol.1999; 38: 841—847.Glenn Haugeberg, Till Uhlig, Jan A. Falch, Jonah I. Halse, and Tore K. Kvien Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis. Results from 394 Patients in the Oslo County Rheumatoid Arthritis Register. Arthritis & Rheumatism Vol.43, No.3, March 2000, 522—530.Glenn Haugeberg, Till Uhlig, Jan A. Falch, Jonah I. Halse, and Tore K. Kvien Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis. Results from 394 Patients in the Oslo County Rheumatoid Arthritis Register. Arthritis & Rheumatism Vol.43, No.3, March 2000, 522—530.Tourinho TF, Stein A, Castro JA, Brenol JC. Rheumatoid arthritis: evidence for bone loss in premenopausal women. J Rheumatol. 2005 Jun;32(6):1020-5.Tourinho TF, Stein A, Castro JA, Brenol JC. Rheumatoid arthritis: evidence for bone loss in premenopausal women. J Rheumatol. 2005 Jun;32(6):1020-5.Oelzner P, Schwabe A, Lehmann G, Eidner T, Franke S, Wolf G, Hein G. Significance of risk factors for osteoporosis is dependent on gender and menopause in rheumatoid arthritis. Rheumatol Int. 2008 Sep;28(11):1143—50. Epub 2008 Apr 30.Oelzner P, Schwabe A, Lehmann G, Eidner T, Franke S, Wolf G, Hein G. Significance of risk factors for osteoporosis is dependent on gender and menopause in rheumatoid arthritis. Rheumatol Int. 2008 Sep;28(11):1143—50. Epub 2008 Apr 30.Di Munno O, Mazzantini M, Sinigaglia L et al.: Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter crosssectional study. J Rheumatol 2004; 31: 1305—9.Di Munno O, Mazzantini M, Sinigaglia L et al.: Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter crosssectional study. J Rheumatol 2004; 31: 1305—9.Deodhar AA, Woolf AD. Bone mass measurement and bone metabolism in rheumatoid arthritis: a review. Br J Rheumatol. 1996 Apr;35(4):309—22. Review.Deodhar AA, Woolf AD. Bone mass measurement and bone metabolism in rheumatoid arthritis: a review. Br J Rheumatol. 1996 Apr;35(4):309—22. Review.Lodder MC, De Jong Z, Kostense PJ et al.: Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density Ann Rheum Dis 2004; 63: 1576—80.Lodder MC, De Jong Z, Kostense PJ et al.: Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density Ann Rheum Dis 2004; 63: 1576—80.Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000 Mar;43(3):522—30.Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000 Mar;43(3):522—30.Kröger H, Tuppurainen M, Honkanen R, Alhava E, Saarikoski S.Bone mineral density and risk factors for osteoporosis-- a population-based study of 1600 perimenopausal women. Calcif Tissue Int. 1994 Jul;55(1):1—7.Kröger H, Tuppurainen M, Honkanen R, Alhava E, Saarikoski S.Bone mineral density and risk factors for osteoporosis-- a population-based study of 1600 perimenopausal women. Calcif Tissue Int. 1994 Jul;55(1):1—7.Rudiger АА, Weiss RJ, Wick MC, Ackermann PW, Montgomery SM. Increased fracture risk in patients with rheumatic disorders and other inflammatory diseases -- a case-control study with 53,108 patients with fracture. J Rheumatol. 2010 Nov;37(11):2247-50. Epub 2010 Oct 1.Rudiger АА, Weiss RJ, Wick MC, Ackermann PW, Montgomery SM. Increased fracture risk in patients with rheumatic disorders and other inflammatory diseases -- a case-control study with 53,108 patients with fracture. J Rheumatol. 2010 Nov;37(11):2247-50. Epub 2010 Oct 1.Van Staa TP, Geusens P, Bijlsma JWJ, Leufkens HGM, Cooper C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:3104—3112.Van Staa TP, Geusens P, Bijlsma JWJ, Leufkens HGM, Cooper C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:3104—3112.Kim SY, Schneeweiss S, Liu J, Daniel GW, Ghang CL, Garneau K, Solomon DH. Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Research & Therapy 2010;12:R154.Kim SY, Schneeweiss S, Liu J, Daniel GW, Ghang CL, Garneau K, Solomon DH. Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Research & Therapy 2010;12:R154.Madsen OR. Ugeskr Laeger. Significance of physical activity for bone mass and fracture risk in patients with rheumatoid arthritis. 2002 Sep 23;164(39):4528—31. Review. Danish.Madsen OR. Ugeskr Laeger. Significance of physical activity for bone mass and fracture risk in patients with rheumatoid arthritis. 2002 Sep 23;164(39):4528—31. Review. Danish.Solomon DH, Finkelstein JS, Shadick N, LeBoff MS, Winalski C et al. The Relationship Between Focal Erosions and Generalized Osteoporosis in Postmenopausal Women with Rheumatoid Arthritis: The Osteoporosis in Rheumatoid Arthritis (OPiRA) Cohort Study. Arthritis Rheum, 2009;60:1624—1631.Solomon DH, Finkelstein JS, Shadick N, LeBoff MS, Winalski C et al. The Relationship Between Focal Erosions and Generalized Osteoporosis in Postmenopausal Women with Rheumatoid Arthritis: The Osteoporosis in Rheumatoid Arthritis (OPiRA) Cohort Study. Arthritis Rheum, 2009;60:1624—1631.Kaz Kaz H, Johnson D, Kerry S, Chinappen U, Tweed K, Patel S. Fall-related risk factors and osteoporosis in women with rheumatoid arthritis. Rheumatology 2004; 43: 1267—1271.Kaz Kaz H, Johnson D, Kerry S, Chinappen U, Tweed K, Patel S. Fall-related risk factors and osteoporosis in women with rheumatoid arthritis. Rheumatology 2004; 43: 1267—1271.Matthis C, Weber U, O'Neill TW, Raspe H. Health impact associated with vertebral deformities: results from the European Vertebral Osteoporosis Study (EVOS). Osteoporos Int. 1998;8(4):364—72.).Matthis C, Weber U, O'Neill TW, Raspe H. Health impact associated with vertebral deformities: results from the European Vertebral Osteoporosis Study (EVOS). Osteoporos Int. 1998;8(4):364—72.).Black DM, Arden NK, Palermo L, Pearson J, Cummings SR. Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group. J Bone Miner Res. 1999 May;14(5):821—8.Black DM, Arden NK, Palermo L, Pearson J, Cummings SR. Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group. J Bone Miner Res. 1999 May;14(5):821—8.Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R. Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis. 1995 Oct;54(10):801—6.Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R. Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis. 1995 Oct;54(10):801—6.Huusko TM, Korpela M, Karppi P, Avikainen V, Kautiainen H, Sulkava R. Threefold increased risk of hip fractures with rheumatoid arthritis in Central Finland. Ann. 0Rheum Dis 2001, May; 60(5):521—2.Huusko TM, Korpela M, Karppi P, Avikainen V, Kautiainen H, Sulkava R. Threefold increased risk of hip fractures with rheumatoid arthritis in Central Finland. Ann. 0Rheum Dis 2001, May; 60(5):521—2.Белых Е.В., Меньшикова Л.В. Вторичный остеопороз у больных ревматоидным артритом. Научно-практическая ревматология 2000; №4:32.Белых Е.В., Меньшикова Л.В. Вторичный остеопороз у больных ревматоидным артритом. Научно-практическая ревматология 2000; №4:32.Дыдыкина И.С., Беневоленская Л.И., Гавва Т.Н., Маслова К.А Ревматоидный артрит и переломы. IV Съезд ревматологов России: Тезисы. — Научно-практическая ревматология. 2005; 3: 38, № 144.Дыдыкина И.С., Беневоленская Л.И., Гавва Т.Н., Маслова К.А Ревматоидный артрит и переломы. IV Съезд ревматологов России: Тезисы. — Научно-практическая ревматология. 2005; 3: 38, № 144.N. Saidenberg-Kermanac’ha, A. Corradob, D. Lemeitera, M.C. deVernejoulb, M.C. Boissiera, M.E. Cohen. TNF-a antibodies and osteoprotegerin decrease systemic bone loss associated with inflammation through distinct mechanisms in collagen-induced arthritis. Solalb Received *, 8 April 2004; revised 1 July 2004; accepted 7 July 2004 Bone 35 (2004) 1200—1207.N. Saidenberg-Kermanac’ha, A. Corradob, D. Lemeitera, M.C. deVernejoulb, M.C. Boissiera, M.E. Cohen. TNF-a antibodies and osteoprotegerin decrease systemic bone loss associated with inflammation through distinct mechanisms in collagen-induced arthritis. Solalb Received *, 8 April 2004; revised 1 July 2004; accepted 7 July 2004 Bone 35 (2004) 1200—1207.Cheryl Barnabe, MD, David A. Hanley. Effect of Tumor Necrosis Factor Alpha Inhibition on Bone Density and Turnover Markers in Patients with Rheumatoid Arthritis and Spondyloarthropathy. 2008 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 39:116—122.Cheryl Barnabe, MD, David A. Hanley. Effect of Tumor Necrosis Factor Alpha Inhibition on Bone Density and Turnover Markers in Patients with Rheumatoid Arthritis and Spondyloarthropathy. 2008 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 39:116—122.Bruno Seriolo, Sabrina Paolino, Alberto Sulli, Valentino Fer-retti, and Maurizio Cutolo. Bone Metabolism Changes During Anti-TNF-Therapy in Patients with Active Rheumatoid Arthritis Division of Rheumatology, Department of Internal Medicine and Medical Specialities, University of Genova, Italy Ann. N.Y. Acad. Sci. 1069: 420-427 (2006). C 2006 New York Academy of Sciences.Bruno Seriolo, Sabrina Paolino, Alberto Sulli, Valentino Fer-retti, and Maurizio Cutolo. Bone Metabolism Changes During Anti-TNF-Therapy in Patients with Active Rheumatoid Arthritis Division of Rheumatology, Department of Internal Medicine and Medical Specialities, University of Genova, Italy Ann. N.Y. Acad. Sci. 1069: 420-427 (2006). C 2006 New York Academy of Sciences.Norihiro Nishimoto, Jun Hashimoto, Nobuyuki Miyasaka, Kazuhiko Yamamoto, Shinichi Kawai, Tsutomu Takeuchi, Norikazu Murata, Désirée van der Heijde and Tadamitsu Kishimoto. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 2007;66;1162—1167.Norihiro Nishimoto, Jun Hashimoto, Nobuyuki Miyasaka, Kazuhiko Yamamoto, Shinichi Kawai, Tsutomu Takeuchi, Norikazu Murata, Désirée van der Heijde and Tadamitsu Kishimoto. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 2007;66;1162—1167.E. Terpos, K. Fragiadaki, M. Konsta, C. Bratengeier, A. Papatheodorou, PP. Sfikakis Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis. Clinical and Experimental Rheumatology 2011; 29: 921—925.E. Terpos, K. Fragiadaki, M. Konsta, C. Bratengeier, A. Papatheodorou, PP. Sfikakis Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis. Clinical and Experimental Rheumatology 2011; 29: 921—925.Maria J H Boumans, Rogier M Thurlings, Lorraine Yeo, Dagmar Scheel-Toellner, Koen Vos, Danielle M Gerlag, Paul P Tak. Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis Ann Rheum Dis 2012;71:108—113.Maria J H Boumans, Rogier M Thurlings, Lorraine Yeo, Dagmar Scheel-Toellner, Koen Vos, Danielle M Gerlag, Paul P Tak. Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis Ann Rheum Dis 2012;71:108—113.Stanley B. Cohen, Robin K. Dore, Nancy E. Lane, Peter A. Ory, Charles G. Peterfy, John T. Sharp et al. Denosumab Treatment Effects on Structural Damage, Bone Mineral Density, and Bone Turnover in Rheumatoid Arthritis. A 12-month, Multicenter, Randomized, DoubleBlind, Placebo-Controlled, Phase II Clinical Trial. Arthritis&Rheumatism Vol.58, No.5, May 2008, pp 1299—1309.Stanley B. Cohen, Robin K. Dore, Nancy E. Lane, Peter A. Ory, Charles G. Peterfy, John T. Sharp et al. Denosumab Treatment Effects on Structural Damage, Bone Mineral Density, and Bone Turnover in Rheumatoid Arthritis. A 12-month, Multicenter, Randomized, DoubleBlind, Placebo-Controlled, Phase II Clinical Trial. Arthritis&Rheumatism Vol.58, No.5, May 2008, pp 1299—1309.Robin K Dore, Stanley B Cohen, Nancy E Lane, William Palmer, William Shergy et al. Effects of denosumab on bone mineral density and bone turnover in patients with RA receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis 2010; 69: 872—875.Robin K Dore, Stanley B Cohen, Nancy E Lane, William Palmer, William Shergy et al. Effects of denosumab on bone mineral density and bone turnover in patients with RA receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis 2010; 69: 872—875.

The authors declare that there are no conflicts of interest present.