Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study.
OBJECTIVE
To determine the changes in bone mineral density (BMD) in patients with rheumatoid arthritis (RA; without osteoporosis) treated with infliximab.


METHODS
Twenty-six patients (19 women, seven men) aged 54.2 yr (range 27-75), with persistently active RA despite a high dose of non-steroidal anti-inflammatory drugs and/or treatment with methotrexate or leflunomide, were studied. Mean duration of disease was 9.8 yr. Patients receiving or having received bisphosphonates or hormone replacement therapy were excluded. The patients were treated with 3.5 mg/kg infliximab at weeks 0, 2, 6 and then every 6-8 weeks. Lumbar and femoral BMD was measured by dual-energy X-ray absorptiometry at baseline and 12 months later. Serum osteocalcin and serum crosslaps were measured at baseline (week 0) and after 12 months. Twelve patients were taking calcium (1 g/day) and vitamin D (800 IU/day). Twenty patients were receiving methotrexate (mean dose 12.5 mg/day), six patients were receiving leflunomide (mean dose 20 mg/day) and nine patients were concomitantly receiving corticosteroids at a mean daily dose of 10 mg.


RESULTS
After 12 months of infliximab therapy, there was a significant increase in BMD in the spine (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.001) and the femoral neck (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.01). With regard to the root mean square average, there was a significant increase in BMD at the left femoral neck (11.6% for a root mean square of 6%) but only a trend towards improvement in the spine (2.7% for a root mean square of 4%) during the study period. There was a significant increase in osteocalcin serum levels between baseline and after 12 months (P < 0.01) and a significant decrease in the marker for bone resorption (P < 0.01) but no change in serum calcium was observed. However, the changes in markers of bone metabolism and BMD were not correlated.


CONCLUSIONS
The data support the hypothesis that anti-TNF therapy may exert beneficial effects on bone metabolism in RA patients.
Lange
U
U
Kerckhoff Clinic and Foundation, Department of Rheumatology, Clinical Immunology and Osteology, Sprudelhof 11, 61231 Bad Nauheim, Germany. U.Lange@kerckhoff-klinik.de
Teichmann
J
J
Müller-Ladner
U
U
Strunk
J
J
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D003094:Collagen / Q000097:blood; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D006801:Humans; D000069285:Infliximab; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015675:Osteocalcin; D003094:Collagen; D000069285:Infliximab