Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis.
OBJECTIVE
To evaluate the relationship between bone mineral density (BMD) and biomarkers of bone turnover and inflammation in patients with ankylosing spondylitis (AS) treated with infliximab.


METHODS
Patients (n = 279) were randomly assigned (3:8) to receive placebo or 5 mg/kg infliximab every 6 weeks through week 96. At week 24, placebo-treated patients crossed over to infliximab 5 mg/kg. Starting at week 36, patients treated with infliximab received dose escalations to 7.5 mg/kg. Hip and spine BMD were measured (baseline, week 24, week 102) using dual-energy x-ray absorptiometry. Sera were analysed (baseline, week 24, week 102) for levels of bone alkaline phosphatase (BAP), osteocalcin, C-terminal cross-linking telopeptide of type I collagen (CTX), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and transforming growth factor-beta.


RESULTS
Patients treated with infliximab showed significantly greater median increases in BMD of the spine (2.5%, p<0.001) and hip (0.5%, p = 0.033) at week 24 than those who received placebo (0.5% and 0.2% respectively). Baseline levels of IL-6, VEGF, osteocalcin, BAP and CTX were significantly correlated with increases in spinal BMD at weeks 24 and 102 in the infliximab group. In a multiple regression analysis, high baseline osteocalcin levels and early increases in BAP at week 2 were significantly associated with increases in BMD scores of the spine (week 102) and hip (weeks 24 and 102) in the infliximab group.


CONCLUSIONS
Patients with AS who received infliximab showed significant increases in BMD scores over 2 years. While many significant correlations were observed between BMD scores of the hip and spine and biomarker levels, high baseline osteocalcin levels and early increases in BAP were consistently associated with increases in BMD scores.
Visvanathan
S
S
Centocor Research and Development, Inc., 200 Great Valley Parkway, Mailstop RA-1-4, Malvern, PA 19355, USA. svisvana@cntus.jnj.com
van der Heijde
D
D
Deodhar
A
A
Wagner
C
C
Baker
D G
DG
Han
J
J
Braun
J
J
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D002574:Cervical Vertebrae / Q000503:physiopathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D000069285:Infliximab; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D015675:Osteocalcin; D000069285:Infliximab; D000469:Alkaline Phosphatase