Effects of TNF Inhibitors on Parathyroid Hormone and Wnt Signaling Antagonists in Rheumatoid Arthritis.
Tumor necrosis factor α inhibitors (TNFi) are the major class of biologic drug used for the treatment of Rheumatoid arthritis (RA). Their effects on inflammation and disease control are well established, but this is not true also for bone metabolism, especially for key factors as parathyroid hormone and Wnt pathway. Those two pathways are gaining importance in the pathogenesis RA bone damage, both systemic and local, but how the new treatment affects them is still largely unknown. We studied 54 RA patients who were starting an anti-TNFα treatment due to the failure of the conventional synthetic disease-modifying antirheumatic drugs. Serum levels of Wnt/βcatenin pathway inhibitors (Dickkopf-related protein 1, Dkk1, and Sclerostin), Parathyroid hormone (PTH), vitamin D, and bone turnover markers were measured at baseline in the morning after fasting and after 6 months of therapy. We found a significant percentage increase in serum PTH (+32 ± 55 %; p = 0.002) and a decrease in Dkk1 mean serum levels (-2.9 ± 12.1; p = 0.05). PTH percentage changes were positively correlated both with C-terminal telopeptide of type I collagen and Dkk1 percentage changes. Sclerostin serum levels showed no significant difference. TNFi treatment provokes in the short term a rise in PTH levels and a decrease in Dkk1 serum levels. The increase of PTH might promote bone resorption and blunt the normalization of Dkk1 serum levels in RA. Those data give a new insight into TNFi metabolic effects on bone and suggest new strategies to achieve better results in terms of prevention of bone erosions and osteoporosis with TNFi treatment in RA.
Rheumatology Section, Department of Medicine, University of Verona, Policlinico G.B Rossi, Piazzale Ludovico Scuro, 10, 37134, Verona, Italy. gio90it90@gmail.com.
Giovanni
0000-0002-8915-0755
G
Adami
Rheumatology Section, Department of Medicine, University of Verona, Policlinico G.B Rossi, Piazzale Ludovico Scuro, 10, 37134, Verona, Italy.
Giovanni
G
Orsolini
Rheumatology Section, Department of Medicine, University of Verona, Policlinico G.B Rossi, Piazzale Ludovico Scuro, 10, 37134, Verona, Italy.
Silvano
S
Adami
Rheumatology Section, Department of Medicine, University of Verona, Policlinico G.B Rossi, Piazzale Ludovico Scuro, 10, 37134, Verona, Italy.
Ombretta
O
Viapiana
Rheumatology Section, Department of Medicine, University of Verona, Policlinico G.B Rossi, Piazzale Ludovico Scuro, 10, 37134, Verona, Italy.
Luca
L
Idolazzi
Rheumatology Section, Department of Medicine, University of Verona, Policlinico G.B Rossi, Piazzale Ludovico Scuro, 10, 37134, Verona, Italy.
Davide
D
Gatti
Rheumatology Section, Department of Medicine, University of Verona, Policlinico G.B Rossi, Piazzale Ludovico Scuro, 10, 37134, Verona, Italy.
Maurizio
M
Rossini
D000068879:Adalimumab / Q000008:administration & dosage; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption; D000068582:Certolizumab Pegol / Q000008:administration & dosage; D024042:Collagen Type I / Q000378:metabolism; D000068800:Etanercept / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010024:Osteoporosis / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors*; D010455:Peptides; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D060449:Wnt Signaling Pathway
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; C052929:collagen type I trimeric cross-linked peptide; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D000068582:Certolizumab Pegol; D008727:Methotrexate
Dkk1; Rheumatoid arthritis; TNF-blocking antibody; Wnt pathway; parathyroid hormone