Login Register Cart 0
Generic placeholder image

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Relation of the Serum Levels of DKK-1 and Osteoprotegerin with Bone Mass in Tightly Controlled Rheumatoid Arthritis

Author(s): Carmen Gómez-Vaquero*, Irene Martín, Andrea Zacarías, Pedro Alía, Estíbaliz Loza, Loreto Carmona and Javier Narváez

Volume 17, Issue 1, 2021

Published on: 21 December, 2020

Page: [101 - 108] Pages: 8

DOI: 10.2174/1573397116666201221112509

Price: $65

Abstract

Objective: To analyze the association between serum levels of osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and the annual percent change (Δ%) in bone mineral density (BMD) in patients with tightly controlled rheumatoid arthritis (RA).

Methods: Observational mixed-study. RA patients followed-up with a tight-control strategy were included. Bone densitometries were performed at baseline (T0) and follow-up (T1) and serum levels of OPG and DKK-1 were measured by ELISA also in T0 and T1; additional clinical variables included disease activity measures, and treatment for RA and osteoporosis. Descriptive bivariate and multivariate analyses, stratified by gender, were performed.

Results: We included 97 RA patients (70% female, with a mean age of 53 years, and 76% with low activity by DAS28); 95% were treated with DMARDs and 37% with anti-osteoporotic drugs. Mean time between T0 and T1 was 2.7 years. Most patients had their BMD improved. The mean Δ%BMD was +0.42% for lumbar spine, +0.15% for femoral neck and +0.91% for total femur. In men, baseline OPG was significantly associated with higher BMD loss (β coefficient -0.64) at the femoral neck. In women, DKK-1 was associated with higher BMD loss at the femoral neck (β coefficient -0.09), and total femur (β coefficient -0.11); however, DKK-1 was associated with lower BMD loss at the lumbar spine (β coefficient 0.06).

Conclusion: In tightly controlled RA patients, we have found no evidence of bone loss. The role of DKK1 and OPG seems small and might be related to sex and location.

Keywords: Rheumatoid arthritis, osteoporosis, bone density, osteoprotegerin, DKK-1, β coefficient.

« Previous Next »
[1]
Deal C. Bone loss in rheumatoid arthritis: Systemic, periarticular, and focal. Curr Rheumatol Rep 2012; 14(3): 231-7.
[http://dx.doi.org/10.1007/s11926-012-0253-7] [PMID: 22527950]
[2]
Vis M, Güler-Yüksel M, Lems WF. Can bone loss in rheumatoid arthritis be prevented? Osteoporos Int 2013; 24(10): 2541-53.
[http://dx.doi.org/10.1007/s00198-013-2334-5] [PMID: 23775419]
[3]
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; 43(3): 522-30.
[http://dx.doi.org/10.1002/1529-0131(200003)43:3<522::AID-ANR7>3.0.CO;2-Y] [PMID: 10728744]
[4]
Nolla JM, Fiter J, Gómez Vaquero C, Mateo L, Valverde J, Roig Escofet D. Study of bone mineral density in postmenopausal women with rheumatoid arthritis treated with low dose glucocorticoids. Med Clin (Barc) 2000; 114(12): 452-3.
[http://dx.doi.org/10.1016/S0025-7753(00)71329-7] [PMID: 10846698]
[5]
van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 2006; 54(10): 3104-12.
[http://dx.doi.org/10.1002/art.22117] [PMID: 17009229]
[6]
Sinigaglia L, Nervetti A, Mela Q, et al. Italian study group on bone mass in rheumatoid arthritis. A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. J Rheumatol 2000; 27(11): 2582-9.
[PMID: 11093437]
[7]
Roux C. Osteoporosis in inflammatory joint diseases. Osteoporos Int 2011; 22(2): 421-33.
[http://dx.doi.org/10.1007/s00198-010-1319-x] [PMID: 20552328]
[8]
Arboleya L, Castañeda S. Osteoimmunology: The study of the relationship between the immune system and bone tissue. Reumatol Clin 2013; 9(5): 303-15.
[http://dx.doi.org/10.1016/j.reuma.2013.02.008] [PMID: 23727459]
[9]
Geusens PP, Landewé RB, Garnero P, et al. The ratio of circulating osteoprotegerin to RANKL in early rheumatoid arthritis predicts later joint destruction. Arthritis Rheum 2006; 54(6): 1772-7.
[http://dx.doi.org/10.1002/art.21896] [PMID: 16736519]
[10]
Xu S, Wang Y, Lu J, Xu J. Osteoprotegerin and RANKL in the pathogenesis of rheumatoid arthritis-induced osteoporosis. Rheumatol Int 2012; 32(11): 3397-403.
[http://dx.doi.org/10.1007/s00296-011-2175-5] [PMID: 22057136]
[11]
Schett G, Saag KG, Bijlsma JW. From bone biology to clinical outcome: state of the art and future perspectives. Ann Rheum Dis 2010; 69(8): 1415-9.
[http://dx.doi.org/10.1136/ard.2010.135061] [PMID: 20650876]
[12]
Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13(2): 156-63.
[http://dx.doi.org/10.1038/nm1538] [PMID: 17237793]
[13]
Rossini M, Viapiana O, Adami S, et al. In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathyroid hormone, bone erosions and bone mineral density. Clin Exp Rheumatol 2015; 33(1): 77-83.
[PMID: 25438096]
[14]
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62(9): 2569-81.
[http://dx.doi.org/10.1002/art.27584] [PMID: 20872595]
[15]
Sen D, Brasington R. Tight disease control in early RA. Rheum Dis Clin North Am 2012; 38(2): 327-43.
[http://dx.doi.org/10.1016/j.rdc.2012.04.004] [PMID: 22819087]
[16]
Biomedica Immunoassays – Bone Metabolism. Available from: http://www.bmgrp.com/products/bone-metabolism/osteoprotegerin-elisa
[17]
Diaz Curiel M, Carrasco de la Peña JL, Honorato Perez J, Perez Cano R, Rapado A, Ruiz Martinez I. Study of bone mineral density in lumbar spine and femoral neck in a Spanish population. Multicentre Research Project on Osteoporosis. Osteoporos Int 1997; 7(1): 59-64.
[http://dx.doi.org/10.1007/BF01623462] [PMID: 9102065]
[18]
Shepherd JA, Schousboe JT, Broy SB, Engelke K, Leslie WD. Executive summary of the 2015 iscd position development conference on advanced measures from dxa and QCT: Fracture prediction beyond BMD. J Clin Densitom 2015; 18(3): 274-86.
[http://dx.doi.org/10.1016/j.jocd.2015.06.013] [PMID: 26277847]
[19]
Liu YY, Long L, Wang SY, et al. Circulating Dickkopf-1 and osteoprotegerin in patients with early and longstanding rheumatoid arthritis. Chin Med J (Engl) 2010; 123(11): 1407-12.
[PMID: 20819596]
[20]
Goldring SR, Gravallese EM. Mechanisms of bone loss in inflammatory arthritis: Diagnosis and therapeutic implications. Arthritis Res 2000; 2(1): 33-7.
[http://dx.doi.org/10.1186/ar67] [PMID: 11094416]
[21]
Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73(3): 492-509.
[http://dx.doi.org/10.1136/annrheumdis-2013-204573] [PMID: 24161836]
[22]
Pinzone JJ, Hall BM, Thudi NK, et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood 2009; 113(3): 517-25.
[http://dx.doi.org/10.1182/blood-2008-03-145169] [PMID: 18687985]
[23]
Aguilar Del Rey FJ, García Portales R, Haro Liger M, Rodríguez Andreu J, Casals Sánchez JL, Pérez González R. Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases. Med Clin (Barc) 2016; 147(2): 56-62.
[http://dx.doi.org/10.1016/j.medcli.2016.03.029] [PMID: 27209224]
[24]
Singh A, Gupta MK, Mishra SP. Study of correlation of level of expression of Wnt signaling pathway inhibitors sclerostin and dickkopf-1 with disease activity and severity in rheumatoid arthritis patients. Drug Discov Ther 2019; 13(1): 22-7.
[http://dx.doi.org/10.5582/ddt.2019.01011] [PMID: 30880318]
[25]
Briot K, Rouanet S, Schaeverbeke T, et al. The effect of tocilizumab on bone mineral density, serum levels of Dickkopf-1 and bone remodeling markers in patients with rheumatoid arthritis. Joint Bone Spine 2015; 82(2): 109-15.
[http://dx.doi.org/10.1016/j.jbspin.2014.10.015] [PMID: 25557658]
[26]
Honsawek S, Tanavalee A, Yuktanandana P, Ngarmukos S, Saetan N, Tantavisut S. Dickkopf-1 (Dkk-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients. BMC Musculoskelet Disord 2010; 11: 257.
[http://dx.doi.org/10.1186/1471-2474-11-257] [PMID: 21062498]
[27]
Haugeberg G, Helgetveit KB, Førre Ø, Garen T, Sommerseth H, Prøven A. Generalized bone loss in early rheumatoid arthritis patients followed for ten years in the biologic treatment era. BMC Musculoskelet Disord 2014; 15: 289.
[http://dx.doi.org/10.1186/1471-2474-15-289] [PMID: 25182527]
[28]
Voorzanger-Rousselot N, Journe F, Doriath V, Body JJ, Garnero P. Assessment of circulating Dickkopf-1 with a new two-site immunoassay in healthy subjects and women with breast cancer and bone metastases. Calcif Tissue Int 2009; 84(5): 348-54.
[http://dx.doi.org/10.1007/s00223-009-9225-y] [PMID: 19252761]
[29]
Vik A, Mathiesen EB, Brox J, et al. Serum osteoprotegerin is a predictor for incident cardiovascular disease and mortality in a general population: The Tromsø Study. J Thromb Haemost 2011; 9(4): 638-44.
[http://dx.doi.org/10.1111/j.1538-7836.2011.04222.x] [PMID: 21284802]
[30]
Guañabens N, Gifre L, Peris P. The role of Wnt signaling and sclerostin in the pathogenesis of glucocorticoid-induced osteoporosis. Curr Osteoporos Rep 2014; 12(1): 90-7.
[http://dx.doi.org/10.1007/s11914-014-0197-0] [PMID: 24488619]
[31]
Bijlsma JW, Boers M, Saag KG, Furst DE. Glucocorticoids in the treatment of early and late RA. Ann Rheum Dis 2003; 62(11): 1033-7.
[http://dx.doi.org/10.1136/ard.62.11.1033] [PMID: 14583563]
[32]
Verhoeven AC, Boers M. Limited bone loss due to corticosteroids; a systematic review of prospective studies in rheumatoid arthritis and other diseases. J Rheumatol 1997; 24(8): 1495-503.
[PMID: 9263141]
[33]
Book C, Karlsson M, Akesson K, Jacobsson L. Disease activity and disability but probably not glucocorticoid treatment predicts loss in bone mineral density in women with early rheumatoid arthritis. Scand J Rheumatol 2008; 37(4): 248-54.
[http://dx.doi.org/10.1080/03009740801998747] [PMID: 18612924]
[34]
Zerbini CAF, Clark P, Mendez-Sanchez L, et al. IOF Chronic inflammation and bone structure (CIBS) working group. Biologic therapies and bone loss in rheumatoid arthritis. Osteoporos Int 2017; 28(2): 429-46.
[http://dx.doi.org/10.1007/s00198-016-3769-2] [PMID: 27796445]
[35]
Zhang J, Redden DT, McGwin G Jr, et al. Consortium for the longitudinal evaluations of african americans with early rheumatoid arthritis investigators. Generalized bone loss as a predictor of three year radiographic damage in African American patients with recent onset rheumatoid arthritis. Arthritis Rheum 2010; 62(8): 2219-26.
[http://dx.doi.org/10.1002/art.27510] [PMID: 20506234]
[36]
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(12): 1576-80.
[http://dx.doi.org/10.1136/ard.2003.016253] [PMID: 15547081]
[37]
Reina D, Gómez-Vaquero C, Díaz-Torné C, Solé JMN. Rheumatology service hospital Moisès Broggi.. Assessment of nutritional status by dual X-Ray absorptiometry in women with rheumatoid arthritis: A case-control study. Medicine 2019; 98(6): e14361.
[http://dx.doi.org/10.1097/MD.0000000000014361] [PMID: 30732168]

Rights & Permissions Print Cite
Article Metrics
15
2
© 2024 Bentham Science Publishers | Privacy Policy