[Are there any positive effects of TNF-alpha blockers on bone metabolism?].
Secondary osteoporosis (OP) is a well-recognized complication of rheumatoid arthritis (RA). Treatment with TNF-alpha blockers, might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular regions.


OBJECTIVE
To assess the influence of anti-TNF-alpha therapy, on bone metabolism in RA patients. 36 RA patients were treated with stable therapy of prednisone (7.5 mg/day) and methotrexate (MTX=10 mg/week). Nine of these RA patients further received etanercept (25 mg, twice/weekly) and eleven infliximab (3mg/kg on 0, 2, 6, and every 8 weeks thereafter). A control group included 16 RA patients only with stable therapy (some dosage of prednisone and MTX). Quantitative Ultrasound (QUS) bone densitometry was obtained at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy). Bone mineral density (BMD) of the hip and lumbar spine were performed with a densitometer ( Lunar Prodigy, GE, USA) at baseline and after 12 months. Soluble bone turnover markers [osteocalcin (OC), bone alkaline phospatase (ALP) deoxypyridinoline/creatinine ratio (Dpd/Cr) and cross-linked N-telopeptide of type I collagen / creatinine ratio (NTx/Cr)] were measured using ELISA tests.


RESULTS
AD-SoS values were found increased by +4.55% after 12 months of treatment in the RA patients treated with anti-TNF-alpha therapy. On the contrary, the Ad-SoS levels decreased by -4.48% during the same period in the control RA group. BMD increased by +3.64% at lumbar spine and +2.90% at the hip (both p<0.001) in TNF-alpha blockers-treated patients and decreased by -2.89% and -3.10% (both p<0.001, respectively at lumbar spine and at the hip) in RA patients without anti-TNF-alpha therapy. In RA patients treated with TNF-alpha blockers, OC and bone ALP levels were found significantly increased (p<0.01) and Dpd/Cr or NTx/Cr levels were found significantly decreased (p<0.01) at 12 months when compared to baseline values.


CONCLUSIONS
During 12 months of treatment of RA patients with TNF-alpha blockers, bone formation seems increased while bone resorption seems decreased. The reduced rate of OP seems supported by the same mechanisms involved in the decreased bone joint resorption during anti-TNF-alpha therapy (i.e. increase of osteoblastic activity and decrease osteoclastic activity).
Seriolo
B
B
Clinica Reumatologica, Dipartimento Medicina Interna e Specialità Mediche, Università di Genova, Italia. seriolob@unige.it
Paolino
S
S
Sulli
A
A
Cutolo
M
M
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015992:Body Mass Index; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D003720:Densitometry; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000069285:Infliximab; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014463:Ultrasonography
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept; D011241:Prednisone; D008727:Methotrexate