Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis.

25-hydroxy-vitamin D Bone loss DXA JAK inhibitors Osteocalcin Osteoporosis Osteoprotegerin QCT Rheumatoid arthritis Tofacitinib

Journal

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
ISSN: 1433-2965
Titre abrégé: Osteoporos Int
Pays: England
ID NLM: 9100105

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 27 11 2020
accepted: 01 02 2021
pubmed: 10 2 2021
medline: 24 8 2021
entrez: 9 2 2021
Statut: ppublish

Résumé

Janus kinase (JAK) inhibitors are used to treat rheumatoid arthritis (RA). We assessed the effects of tofacitinib on bone density and bone markers in association with clinical and laboratory parameters in RA. Tofacitinib stabilized bone density and resulted in a positive balance of bone turnover. Janus kinase (JAK) inhibitors emerged as new therapeutic options in rheumatoid arthritis (RA). We have little information on how it affects areal and volumetric bone mineral density (BMD) and bone turnover markers. The aim of this study was to assess the effects of 1-year tofacitinib therapy on bone metabolism in RA. Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) levels, as well as serum levels of sclerostin, osteocalcin (OC), P1NP, DKK-1, OPG, RANKL, and 25-hydroxy-vitamin D3. Areal and volumetric BMD were assessed by DXA and peripheral quantitative CT (QCT), respectively. Twenty-six patients (13 on each arm) completed the study. Tofacitinib was clinically effective by suppressing DAS28, CRP, and HAQ. This was accompanied by the attenuation of further bone loss. Tofacitinib therapy significantly increased OC, OPG, and vitamin D3, while decreased CTX levels (p < 0.05). Age and multiple bone markers (OC, CTX, P1NP, RANKL) inversely correlated with L2-4 and femoral neck BMD by DXA. CRP, DAS28, and RANKL inversely determined volumetric BMD by QCT. Age, CRP, anti-CCP, and DKK-1 influenced the effects of tofacitinib therapy on BMD changes. One-year tofacitinib treatment stabilized BMD in RA patients and resulted in a positive balance of bone turnover as indicated by bone biomarkers. Further studies are needed to evaluate the potential beneficial effects of JAK inhibitors on inflammatory bone loss.

Identifiants

pubmed: 33559714
doi: 10.1007/s00198-021-05871-0
pii: 10.1007/s00198-021-05871-0
pmc: PMC8376736
doi:

Substances chimiques

Piperidines 0
Pyrimidines 0
Pyrroles 0
tofacitinib 87LA6FU830

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1621-1629

Subventions

Organisme : European Union
ID : TAMOP-4.2.4.A/2-11/1-2012-0001
Organisme : European Union
ID : GINOP-2.3.2-15-2016-00015
Organisme : Pfizer
ID : WI188341

Informations de copyright

© 2021. The Author(s).

Références

Autoimmun Rev. 2017 Mar;16(3):313-320
pubmed: 28159704
Nat Rev Rheumatol. 2016 Jan;12(1):63-8
pubmed: 26656659
Clin Rheumatol. 2020 Mar;39(3):727-736
pubmed: 31970549
Ann Rheum Dis. 2006 Nov;65(11):1495-9
pubmed: 16606653
PLoS One. 2017 Jul 14;12(7):e0181126
pubmed: 28708884
Semin Arthritis Rheum. 2010 Apr;39(5):369-83
pubmed: 19095294
Ann Rheum Dis. 2008 Mar;67(3):353-7
pubmed: 17644538
Nat Clin Pract Rheumatol. 2008 Sep;4(9):473-80
pubmed: 18756273
Ann Rheum Dis. 1989 Jul;48(7):535-8
pubmed: 2774695
Curr Rheumatol Rep. 2012 Jun;14(3):231-7
pubmed: 22527950
J Clin Densitom. 2008 Jan-Mar;11(1):123-62
pubmed: 18442757
Expert Opin Pharmacother. 2020 Oct;21(14):1725-1737
pubmed: 32605401
Nat Rev Rheumatol. 2009 Dec;5(12):667-76
pubmed: 19884898
Arthritis Rheum. 2012 Nov;64(11):3531-42
pubmed: 22899318
Sci Transl Med. 2020 Feb 12;12(530):
pubmed: 32051226
Nature. 2003 May 15;423(6937):337-42
pubmed: 12748652
Orthop Clin North Am. 1985 Jul;16(3):557-68
pubmed: 3892413
Semin Nucl Med. 1987 Oct;17(4):316-33
pubmed: 3317846
Nat Rev Rheumatol. 2012 Nov;8(11):656-64
pubmed: 23007741
Ann N Y Acad Sci. 2006 Jun;1069:420-7
pubmed: 16855169
Int J Mol Sci. 2020 Jan 29;21(3):
pubmed: 32013232
Methods. 2006 Apr;38(4):317-23
pubmed: 16481199
Clin Rheumatol. 2020 Jan;39(1):167-175
pubmed: 31522318
J Rheumatol. 2007 Aug;34(8):1753-9
pubmed: 17610317
Front Med (Lausanne). 2020 Dec 01;7:613720
pubmed: 33335907
Arthritis Rheumatol. 2019 Jun;71(6):878-891
pubmed: 30666826
Nat Rev Rheumatol. 2017 Apr;13(4):234-243
pubmed: 28250461
Rheumatology (Oxford). 2018 Aug 1;57(8):1461-1471
pubmed: 28968875
J Rheumatol. 2016 Oct;43(10):1911-1913
pubmed: 27698105
Lancet. 1994 Jul 2;344(8914):23-7
pubmed: 7912297
Nat Clin Pract Rheumatol. 2005 Nov;1(1):47-54
pubmed: 16932627
Osteoporos Int. 2017 Apr;28(4):1271-1277
pubmed: 27942777
Arthritis Rheum. 2013 Mar;65(3):559-70
pubmed: 23348607
Pharmacol Res. 2020 Feb;152:104609
pubmed: 31862477
Ann Rheum Dis. 2020 Jun;79(6):685-699
pubmed: 31969328
Ann Rheum Dis. 2010 Sep;69(9):1580-8
pubmed: 20699241
J Immunol. 2015 Jan 1;194(1):21-7
pubmed: 25527793
Ann Rheum Dis. 1998 Jun;57(6):325-7
pubmed: 9771204
Nat Med. 2007 Feb;13(2):156-63
pubmed: 17237793
Ann Rheum Dis. 2004 Nov;63 Suppl 2:ii67-ii71
pubmed: 15479876
Ann Rheum Dis. 2016 Jun;75(6):1024-33
pubmed: 27002108

Auteurs

A Hamar (A)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Z Szekanecz (Z)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. szekanecz.zoltan@med.unideb.hu.

A Pusztai (A)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

M Czókolyová (M)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

E Végh (E)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Z Pethő (Z)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

N Bodnár (N)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

K Gulyás (K)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Á Horváth (Á)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

B Soós (B)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

L Bodoki (L)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

H P Bhattoa (HP)

Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

G Nagy (G)

Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

G Tajti (G)

Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

G Panyi (G)

Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

É Szekanecz (É)

Department of Oncology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

A Domján (A)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

K Hodosi (K)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

S Szántó (S)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Sports Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

G Szűcs (G)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

S Szamosi (S)

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

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