nach oben

Erschienen in:

22.07.2023 | Original Article

Denosumab improves bone mineral density and microarchitecture in rheumatoid arthritis: randomized controlled trial by HR-pQCT

verfasst von: Ko Chiba, Naoki Iwamoto, Kounosuke Watanabe, Kazuteru Shiraishi, Kengo Saito, Naoki Okubo, Atsushi Kawakami, Makoto Osaki

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 6/2023

Einloggen, um Zugang zu erhalten

Abstract

Introduction

This pre-specified exploratory analysis investigated the effect of denosumab on bone mineral density (BMD) and bone microarchitecture in patients with rheumatoid arthritis (RA) treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).

Materials and methods

In this open-label, parallel-group study, patients were randomly assigned (1:1) to continuous treatment with csDMARDs plus denosumab or continuous treatment with csDMARD therapy alone for 12 months. BMD and bone microarchitecture were measured by dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT).

Results

Of 46 patients enrolled in the primary study, 43 were included in the full analysis set. The mean age was 65.3 years, 88.4% were female, and 60.5% had osteoporosis. Areal BMD of the lumbar spine increased from baseline to 6 and 12 months in both groups, but the increase was higher in the csDMARDs plus denosumab group. Areal BMD of the total hip and femoral neck increased from baseline to 6 and 12 months only in the csDMARDs plus denosumab group. Cortical volumetric BMD and cortical thickness of the distal tibia increased in the csDMARDs plus denosumab group at 6 and 12 months but decreased in the csDMARD therapy alone group. Trabecular bone parameters of the distal tibia improved only in the csDMARDs plus denosumab group at 12 months.

Conclusion

Denosumab may be recommended for patients with RA treated with csDMARDs to increase BMD and improve bone microarchitecture.

Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK (2000) Reduced bone mineral density in male rheumatoid arthritis patients: Frequencies and associations with demographic and disease variables in ninety-four patients in the Oslo County Rheumatoid Arthritis Register. Arthritis Rheum 43:2776–2784CrossRefPubMed

Hauser B, Riches PL, Wilson JF, Horne AE, Ralston SH (2014) Prevalence and clinical prediction of osteoporosis in a contemporary cohort of patients with rheumatoid arthritis. Rheumatology (Oxford) 53:1759–1766CrossRefPubMed

Wright NC, Lisse JR, Walitt BT, Eaton CB, Chen Z, Women’s Health Initiative Investigators (2011) Arthritis increases the risk for fractures—results from the Women’s Health Initiative. J Rheumatol 38:1680–1688CrossRefPubMedPubMedCentral

Kim D, Cho SK, Choi CB, Jun JB, Kim TH, Lee HS, Lee J, Lee SS, Yoo DH, Yoo WH, Sung YK, Bae SC (2016) Incidence and risk factors of fractures in patients with rheumatoid arthritis: an Asian prospective cohort study. Rheumatol Int 36:1205–1214CrossRefPubMed

Wang Y, Hao YJ, Deng XR, Li GT, Geng Y, Zhao J, Zhou W, Zhang ZL (2015) Risk factors for bone mineral density changes in patients with rheumatoid arthritis and fracture risk assessment (in Chinese). Beijing Da Xue Xue Bao Yi Xue Ban 47:781–786PubMed

Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397CrossRefPubMedPubMedCentral

Furuya T, Hosoi T, Saito S, Inoue E, Taniguchi A, Momohara S, Yamanaka H (2011) Fracture risk assessment and osteoporosis treatment disparities in 3,970 Japanese patients with rheumatoid arthritis. Clin Rheumatol 30:1105–1111CrossRefPubMed

Fujimaki H, Nakazawa A, Hirano M, Takeuchi T, Kadowaki A, Kusayama Y, Ide M, Kanai K, Kim Y, Matsubara J, Kumagai K, Inaba Y (2021) Status of fracture risk assessment and osteoporosis treatment in Japanese patients with rheumatoid arthritis. Mod Rheumatol 31:987–991CrossRefPubMed

Ochi K, Inoue E, Furuya T, Ikari K, Toyama Y, Taniguchi A, Yamanaka H, Momohara S (2015) Ten-year incidences of self-reported non-vertebral fractures in Japanese patients with rheumatoid arthritis: discrepancy between disease activity control and the incidence of non-vertebral fracture. Osteoporos Int 26:961–968CrossRefPubMed

10.

NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795CrossRef

11.

Klose-Jensen R, Tse JJ, Keller KK, Barnabe C, Burghardt AJ, Finzel S, Tam LS, Hauge EM, Stok KS, Manske SL (2020) High-resolution peripheral quantitative computed tomography for bone evaluation in inflammatory rheumatic disease. Front Med (Lausanne) 7:337CrossRefPubMed

12.

Boutroy S, Bouxsein ML, Munoz F, Delmas PD (2005) In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 90:6508–6515CrossRefPubMed

13.

Burghardt AJ, Lee CH, Kuo D, Majumdar S, Imboden JB, Link TM, Li X (2013) Quantitative in vivo HR-pQCT imaging of 3D wrist and metacarpophalangeal joint space width in rheumatoid arthritis. Ann Biomed Eng 41:2553–2564CrossRefPubMed

14.

Sundh D, Mellstrom D, Nilsson M, Karlsson M, Ohlsson C, Lorentzon M (2015) Increased cortical porosity in older men with fracture. J Bone Miner Res 30:1692–1700CrossRefPubMed

15.

Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD (2007) Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res 22:425–433CrossRefPubMed

16.

Kostenuik PJ, Nguyen HQ, McCabe J, Warmington KS, Kurahara C et al (2009) Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res 24:182–195CrossRefPubMed

17.

Park JH, Lee NK, Lee SY (2017) Current understanding of RANK signaling in osteoclast differentiation and maturation. Mol Cells 40:706–713PubMedPubMedCentral

18.

Zaheer S, LeBoff M, Lewiecki EM (2015) Denosumab for the treatment of osteoporosis. Expert Opin Drug Metab Toxicol 11:461–470CrossRefPubMedPubMedCentral

19.

Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R, Denosumab Rheumatoid Arthritis Study Group (2008) 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 58:1299–1309CrossRefPubMed

20.

Takeuchi T, Tanaka Y, Ishiguro N, Yamanaka H, Yoneda T, Ohira T, Okubo N, Genant HK, van der Heijde D (2016) Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial. Ann Rheum Dis 75:983–990CrossRefPubMed

21.

Takeuchi T, Tanaka Y, Soen S, Yamanaka H, Yoneda T, Tanaka S, Nitta T, Okubo N, Genant HK, van der Heijde D (2019) Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial. Ann Rheum Dis 78:899–907CrossRefPubMed

22.

Daiichi Sankyo Co., Ltd. (2017) Press release: Daiichi Sankyo obtains approval for additional indication for PRALIA^® subcutaneous injection 60 mg syringe. https://www.daiichisankyo.com/media/press_release/detail/index_3343.html. Accessed 23 Sep 2022

23.

Orimo H, Japan Osteoporosis Society(2015) Japanese 2015 guidelines for the prevention and treatment of osteoporosis (in Japanese). http://www.josteo.com/ja/guideline/doc/15_1.pdf. Accessed 23 Sep 2022

24.

Zebaze RM, Libanati C, Austin M, Ghasem-Zadeh A, Hanley DA, Zanchetta JR, Thomas T, Boutroy S, Bogado CE, Bilezikian JP, Seeman E (2014) Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone 59:173–179CrossRefPubMed

25.

Iwamoto N, Chiba K, Sato S, Shiraishi K, Watanabe K, Oki N, Okada A, Koga T, Kawashiri SY, Tamai M, Hosogaya N, Furuyama M, Kobayashi M, Saito K, Okubo N, Uetani M, Osaki M, Kawakami A (2022) Inhibition of bone erosion, determined by high-resolution peripheral quantitative computed tomography (HR-pQCT), in rheumatoid arthritis patients receiving a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab vs csDMARD therapy alone: an open-label, randomized, parallel-group study. Arthritis Res Ther 24:264CrossRefPubMedPubMedCentral

26.

Iwamoto N, Sato S, Sumiyoshi R, Chiba K, Miyamoto N, Arinaga K, Kobayashi M, Yamamoto H, Osaki M, Kawakami A (2019) Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT. Trials 20:494CrossRefPubMedPubMedCentral

27.

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69:1580–1588CrossRefPubMed

28.

Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMed

29.

Whittier DE, Boyd SK, Burghardt AJ, Paccou J, Ghasem-Zadeh A, Chapurlat R, Engelke K, Bouxsein ML (2020) Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int 31:1607–1627CrossRefPubMedPubMedCentral

30.

Pialat J, Burghardt AJ, Sode M, Link TM, Majumdar S (2012) Visual grading of motion induced image degradation in high resolution peripheral computed tomography: impact of image quality on measures of bone density and micro-architecture. Bone 50:111–118CrossRefPubMed

31.

Saigusa Y, Eguchi S, Komori O (2022) Generalized quasi-linear mixed-effects model. Stat Methods Med Res 31:1280–1291CrossRefPubMed

32.

Yagita M, Morita T, Kumanogoh A (2021) Therapeutic efficacy of denosumab for rheumatoid arthritis: a systematic review and meta-analysis. Rheumatol Adv Pract 5:rkab099CrossRefPubMedPubMedCentral

33.

Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK, Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J (2010) Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 25:1886–1894CrossRefPubMedPubMedCentral

34.

Hu YJ, Chines A, Shi Y, Seeman E, Guo XE (2022) The effect of denosumab and alendronate on trabecular plate and rod microstructure at the distal tibia and radius: a post-hoc HR-pQCT study. Bone 154:116187CrossRefPubMed

35.

Ramchand SK, David NL, Lee H, Bruce M, Bouxsein ML, Leder BZ, Tsai JN (2021) Effects of combination denosumab and high-dose teriparatide administration on bone microarchitecture and estimated strength: the DATA-HD HR-pQCT study. J Bone Miner Res 36:41–51CrossRefPubMed

36.

Tsai JN, Nishiyama KK, Lin D, Yuan A, Lee H, Bouxsein ML, Leder BZ (2017) Effects of denosumab and teriparatide transitions on bone microarchitecture and estimated strength: the DATA-switch HR-pQCT study. J Bone Miner Res 32:2001–2009CrossRefPubMed

37.

Yokota K, Chiba K, Okazaki N, Kondo C, Doi M, Yamada S, Era M, Nishino Y, Yonekura A, Tomita M, Osaki M (2020) Deterioration of bone microstructure by aging and menopause in Japanese healthy women: analysis by HR-pQCT. J Bone Miner Metab 38:826–838CrossRefPubMed

38.

Soen S, Fukunaga M, Sugimoto T, Sone T, Fujiwara S, Endo N, Gorai I, Shiraki M, Hagino H, Hosoi T, Ohta H, Yoneda T, Tomomitsu T, Japanese Society for Bone and Mineral Research and Japan Osteoporosis Society Joint Review Committee for the Revision of the Diagnostic Criteria for Primary Osteoporosis (2013) Diagnostic criteria for primary osteoporosis: year 2012 revision. J Bone Miner Metab 31:247–257CrossRefPubMed

Titel: Denosumab improves bone mineral density and microarchitecture in rheumatoid arthritis: randomized controlled trial by HR-pQCT
verfasst von: Ko Chiba
Naoki Iwamoto
Kounosuke Watanabe
Kazuteru Shiraishi
Kengo Saito
Naoki Okubo
Atsushi Kawakami
Makoto Osaki
Publikationsdatum: 22.07.2023
Verlag: Springer Nature Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 6/2023
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-023-01452-9

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Denosumab improves bone mineral density and microarchitecture in rheumatoid arthritis: randomized controlled trial by HR-pQCT