Antiresorptive activity of denosumab in the treatment of osteoporosis in patients with rheumatoid arthritis
https://doi.org/10.14341/osteo9826
Abstract
Background: fracture risks assessment and determination of bone mineral density are modern methods, generally accepted and widely used. However, they have limitations and disadvantages for the dynamic evaluation of bone remodeling processes in RA-patients with low BMD. The investigation of bone resorption markers is an important issue.
Aims: to compare the antiresorptive activity of denosumab and alendronic acid in patients with rheumatoid arthritis and osteoporosis using β-CTX and osteocalcin (OC).
Materials and methods: forty-two patients were included in the study (16 patients were treated with denosumab, 13 patients – with alendronic acid, 13 patients - control group without any osteoporosis treatment). The quantitative determination of β-CTX and OC as well as dual-energy X-ray absorptionometry (DXA) were carried out for all patients at the first visit with consecutive investigation of bone resorption markers 3 months after. The predictive capacity was determined using the ratio of observed fractures/expected fractures by FRAX.
Results: The level of β-CTX 16% (median 861.6 pg/ml vs. 724.6 pg/ml, p = 0.049) and OC 39% (median 13.9 ng/ml vs 8.5 ng/ml, p = 0.047) decreased significantly in 3 month in RA patients treated with denosumab. The decrease of β-CTX (median 858.9 pg/ml vs. 821.8 pg/ml) and OC (median 14.8 ng/ml vs. 13.9 ng/ml) was observed in the group of patients treated with alendronic acid, but not reached statistical significance.
Conclusions: denosumab had showed better antiresorptive activity compared with bisphosphonates, which was registered 3 month after the start of the treatment.
About the Authors
Nadezhda Y. BanshchikovaResearch Institute of Clinical and Experimental Lymphology, a branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
MD
Yelena A. Letyagina
Research Institute of Clinical and Experimental Lymphology, a branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
MD, PhD
Vitaliy O. Omelchenko
Research Institute of Clinical and Experimental Lymphology, a branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
MD
Maksim A. Korolev
Research Institute of Clinical and Experimental Lymphology, a branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
MD, PhD
References
1. Дыдыкина И.С., Коваленко П.С., Смирнов А.В., и др. Опыт применения деносумаба в терапии остеопороза у больных ревматоидным артритом, получающих глюкокортикоиды // Современная ревматология. – 2018. – Т. 2. – №12. – С. 50–57. [Dydykina IS, Kovalenko PS, Smirnov AV, et al. Experience with denosumab therapy for osteoporosis in rheumatoid arthritis patients receiving glucocorticoids. Modern Rheumatology Journal. 2018;12(2):50-57. (In Russ).] doi: 10.14412/1996-7012-2018-2-50-57
2. Лесняк О.М., Марченкова Л.А., Макарова Е.В. Новая тенденция в лечении остеопороза бисфосфонатами – лекарственные каникулы: для кого, когда и как долго? // Лечебное дело. – 2016. – №4. – С. 16–21 [Lesnyak OM, Marchenkova LA, Makarova EV. Novaya tendentsiya v lechenii osteoporoza bisfosfonatami – lekarstvennyye kanikuly: dlya kogo, kogda i kak dolgo? Lechebnoye delo. 2016(4):16-21. (In Russ).]
3. Silverman SL, Schousboe JT, Gold DT. Oral bisphosphonate compliance and persistence: a matter of choice? Osteoporos. Int. 2011;22(1):21-26. doi: 10.1007/s00198-010-1274-6.
4. Lewiecki EM. New and emerging concepts in the use of denosumab for the treatment of osteoporosis. Ther. Adv. Musculoskelet. Dis. 2018;10(11):209-223. doi: 10.1177/1759720X18805759.
5. Miller PD, Pannacciulli N, Brown JP, et al. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J. Clin. Endocrinol. Metab. 2016;101(8):3163-3170. doi: 10.1210/jc.2016-1801.
6. Мокрышева Н.Г., Рожинская Л.Я. Современный взгляд на эффективность терапии постменопаузального остеопороза. Инновационные препараты таргетной терапии // Остеопороз и остеопатии. – 2013. – Т. 16. – №1. – C. 29-33. [Mokrysheva NG, Rozhinskaya LY. Modern view on the effectiveness of therapy for postmenopausal osteoporosis. Innovative drugs of targeted action. Osteoporosis and Bone Diseases. 2013;16(1):29-33. (In Russ).] doi: 10.14341/osteo2013129-33.
7. Дыдыкина П.С., Петрова Е.В., Дыдыкина И.С., и др. Влияние деносумаба на клинико-рентгенологические изменения при ревматоидном артрите. Предварительные результаты // Научно-практическая ревматология. – 2015. – Т. 53. – №2. – С. 134-138. [Dydykina PS, Petrova ЕV, Dydykina IS, et al. Effect of denosumab on clinical and radiological changes in rheumatoid arthritis: preliminary results. Rheumatology Science and Practice. 2015;53(2):134-138. (In Russ).] doi: 10.14412/1995-4484-2015-134-138.
8. Лесняк О.М. Новая парадигма в диагностике и лечении остеопороза: прогнозирование 10-летнего абсолютного риска перелома (калькулятор FRAXTM) // Остеопороз и остеопатии. – 2012. – Т. 15. – №1. – С. 23-28. [Lesnyak OM. The new paradigm in diagnosis and treatment of osteoporosis: prediction of a 10-year absolute risk of fracture (calculator FRAXTM). Osteoporosis and Bone Diseases. 2012;15(1):23-28. (In Russ).] doi: 10.14341/osteo2012123-28.
9. Kanis JA, McCloskey EV, Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos. Int. 2013;24(1):23-57. doi: 10.1007/s00198-012-2074-y.
10. Vasikaran S, Eastell R, Bruyere O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos. Int. 2011;22(2):391-420. doi: 10.1007/s00198-010-1501-1.
11. Morris HA, Eastell R, Jorgensen NR, et al. Clinical usefulness of bone turnover marker concentrations in osteoporosis. Clin. Chim. Acta. 2017;467:34-41. doi: 10.1016/j.cca.2016.06.036.
12. Дрыгина Л.Б., Трофимова Л.И., Саблин О.А., Никифорова И.Д. Современные методы диагностики, профилактики и лечения остеопороза. Методическое пособие. – Санкт-Петербург: ВЦЭРМ им. А.М. Никифорова МЧС России, 2011. [Drygina LB, Trofimova LI, Sablin OA, Nikiforova ID. Sovremennyye metody diagnostiki, profilaktiki i lecheniya osteoporoza. Metodicheskoye posobiye. – Saint Petersburg: VTS·ERM im. A.M. Nikiforova MCHS Rossii; 2011. (In Russ).]
13. Garnero P, Delmas PD. Contribution of bone mineral density and bone turnover markers to the estimation of risk of osteoporotic fracture in postmenopausal women. J. Musculoskelet. Neuronal Interact. 2004;4(1):50-63.
14. Majima T, Komatsu Y, Shimatsu A, et al. Efficacy of combined treatment with raloxifene and alfacalcidol on bone density and biochemical markers of bone turnover in postmenopausal osteoporosis. Endocr. J. 2008;55(1):127-134. doi: 10.1507/endocrj.K07E-027.
15. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N. Engl. J. Med. 2007;356(18):1809-1822. doi: 10.1056/NEJMoa067312.
16. McClung M, Recker R, Miller P, et al. Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone. 2007;41(1):122-128. doi: 10.1016/j.bone.2007.03.011.
17. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N. Engl. J. Med. 2004;350(5):459-468. doi: 10.1056/NEJMoa022436.
18. Saag K, Lindsay R, Kriegman A, et al. A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone. 2007;40(5):1238-1243. doi: 10.1016/j.bone.2007.01.016.
19. Eastell R, Christiansen C, Grauer A, et al. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J. Bone Miner. Res. 2011;26(3):530-537. doi: 10.1002/jbmr.251.
20. Jacques RM, Boonen S, Cosman F, et al. Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-Pivotal Fracture Trial (PFT). J. Bone Miner. Res. 2012;27(8):1627-1634. doi: 10.1002/jbmr.1644.
21. Hannon RA, Eastell R. Biochemical markers of bone turnover and fracture prediction. The journal of the British Menopause Society. 2003;9(1):10-15.
22. Lofman O, Magnusson P, Toss G, Larsson L. Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study. Clin. Chim. Acta. 2005;356(1-2):67-75. doi: 10.1016/j.cccn.2004.12.014.
23. Park SG, Jeong SU, Lee JH, et al. The Changes of CTX, DPD, Osteocalcin, and Bone Mineral Density During the Postmenopausal Period. Annals of rehabilitation medicine. 2018;42(3):441-448. doi: 10.5535/arm.2018.42.3.441.
24. Johansson H, Oden A, Kanis JA, et al. A meta-analysis of reference markers of bone turnover for prediction of fracture. Calcif. Tissue Int. 2014;94(5):560-567. doi: 10.1007/s00223-014-9842-y.
25. Chubb SA, Byrnes E, Manning L, et al. Reference intervals for bone turnover markers and their association with incident hip fractures in older men: the Health in Men study. J. Clin. Endocrinol. Metab. 2015;100(1):90-99. doi: 10.1210/jc.2014-2646.
26. Cejka D, Jager-Lansky A, Kieweg H, et al. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol. Dial. Transplant. 2012;27(1):226-230. doi: 10.1093/ndt/gfr270.
27. Mohamed Y, Haifa H, Datel O, et al. [The role of biochemical markers of bone turnover in the diagnosis of osteoporosis and predicting fracture risk]. Tunis. Med. 2014;92(5):304-310.
28. Reid IR, Brown JP, Burckhardt P, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N. Engl. J. Med. 2002;346(9):653-661. doi: 10.1056/NEJMoa011807.
29. Lu C, Chen Y, Zhang B, et al. Response to teriparatide in Chinese patients with established osteoporosis: osteocalcin and lumbar spine bone-mineral density changes from teriparatide Phase III study. Clin. Interv. Aging. 2017;12:1717-1723. doi: 10.2147/CIA.S140900.
30. Leder BZ, Tsai JN, Uihlein AV, et al. Two years of Denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): a randomized controlled trial. J. Clin. Endocrinol. Metab. 2014;99(5):1694-1700. doi: 10.1210/jc.2013-4440.
31. Paggiosi MA, Peel N, McCloskey E, et al. Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study. Osteoporos. Int. 2014;25(12):2729-2741. doi: 10.1007/s00198-014-2817-z.
32. Naylor KE, Jacques RM, Paggiosi M, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos. Int. 2016;27(1):21-31. doi: 10.1007/s00198-015-3145-7.
33. Мельниченко Г.А., Белая Ж.Е., Рожинская Л.Я., и др. Федеральные клинические рекомендации по диагностике, лечению и профилактике остеопороза // Проблемы Эндокринологии. – 2017. – Т. 63. – №6. – C. 392-426. [Mel’nichenko GA, Belaya ZE, et al. Russian federal clinical guidelines on the diagnostics, treatment, and prevention of osteoporosis. Problems of Endocrinology. 2018;63(6):392-426. (In Russ).] doi: 10.14341/probl2017636392-426
34. Cohen SB, Dore RK, Lane NE, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008;58(5):1299-1309. doi: 10.1002/art.23417.
35. Dore RK, Cohen SB, Lane NE, et al. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann. Rheum. Dis. 2010;69(5):872-875. doi: 10.1136/ard.2009.112920.
Supplementary files
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1. Fig. 1. Dynamics of β-CTX level in patients with RA, receiving therapy with bisphosphonates and denosumab. | |
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2. Fig. 2. Dynamics of osteocalcin level in patients with RA, receiving therapy with bisphosphonates and denosumab. | |
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Type | Исследовательские инструменты | |
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For citations:
Banshchikova N.Y., Letyagina Ye.A., Omelchenko V.O., Korolev M.A. Antiresorptive activity of denosumab in the treatment of osteoporosis in patients with rheumatoid arthritis. Osteoporosis and Bone Diseases. 2018;21(2):4-11. (In Russ.) https://doi.org/10.14341/osteo9826

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