Early onset and effective inhibition of bone resorption in patients with rheumatoid arthritis treated with the tumour necrosis factor alpha antibody infliximab.
OBJECTIVE
To investigate the effect of the tumour necrosis factor alpha antibody infliximab on bone metabolism in patients with rheumatoid arthritis (RA).


METHODS
Twelve RA patients with active disease on a constant dose of methotrexate were treated with a single infusion of infliximab (10 mg/kg BW). Serum beta-CrossLaps and serum osteocalcin as markers of bone resorption and formation were measured two days and one day before and one and 14 days after infliximab infusion with an electrochemiluminiscence immunoassay. RA disease activity was determined using the Disease Activity Score (DAS) and the ACR-response criteria.


RESULTS
Infliximab treatment significantly reduced serum beta-CrossLaps levels from 0.29 +/- 0.13 (mean +/- SD) ng/ml at study entry to 0.17 +/- 0.09 pg/ml one day after infusion (p < 0.005). At day 14 serum beta-CrossLaps levels were still significantly lower compared to pre-treatment levels (0.24 +/- 0.13 pg/ml, p < 0.05). In contrast, serum osteocalcin levels remained unchanged during the observation period (17.8 +/- 9.8 vs 18.2 +/- 9.9 vs 18.6 +/- 12.1 ng/ml, respectively). All but one patient improved clinically after infliximab infusion and the DAS dropped significantly from 6.5 +/- 0.9 prior to treatment to 5.8 +/- 1.3 and 5.0 +/- 1.3 at Day one and 14 days after treatment, respectively. Four patients showed an ACR 20-response one day after therapy and 10 patients 14 days after therapy.


CONCLUSIONS
Infliximab might have potential to inhibit generalised bone loss in patients with RA in addition to its clinical efficacy in reducing disease activity and inhibiting joint destruction.
Hermann
J
J
Division of Rheumatology, Department of Internal Medicine, Karl Franzens University Hospital, Graz, Austria. josef.hermann@kfunigraz.ac.at
Mueller
Th
T
Fahrleitner
A
A
Dimai
H P
HP
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D001862:Bone Resorption / Q000188:drug therapy* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000069285:Infliximab; D008727:Methotrexate