Treatment with infliximab is associated with increased markers of bone formation in patients with Crohn's disease.
OBJECTIVE
Osteoporosis is a common complication of Crohn's disease (CD). Glucocorticoid use and detrimental effects of inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) can lead to osteoporosis. The aim of this study was to assess the ability of treatment with the TNF-alpha antagonist infliximab to increase bone formation as measured by surrogate markers of bone turnover in patients with active CD.


METHODS
Sera from 38 prospectively enrolled CD patients were examined for levels of bone alkaline phosphatase (BAP), N-telopeptide of type I collagen (NTX), immunoreactive parathyroid hormone (iPTH), calcium, and pro-inflammatory cytokines at baseline and 4 weeks following infliximab infusion. Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and glucocorticoid dose also were collected.


RESULTS
In this cohort, CDAI and IBDQ scores were significantly improved at week 4 (P<0.001). Infliximab therapy was associated with an increase in BAP, a marker of bone formation (P=0.010), whereas NTX, a marker of bone resorption, was not increased (P=0.801). Among 22 patients who were taking glucocorticoids, mean glucocorticoid dose decreased 36% (P<0.001; -7.9 mg).


CONCLUSIONS
Treatment with infliximab was associated with increased markers of bone formation (BAP) without increasing bone resorption (NTX). This effect may be due to a beneficial effect of TNF-alpha blockade on bone turnover, a beneficial effect on CD activity resulting in decreased glucocorticoid dose, or both. Studies of longer duration are needed to assess the effect of infliximab on bone mineral density.
Abreu
Maria T
MT
Department of Medicine, Division of Gastroenterology, Inflammatory Bowel Disease Center, Mount Sinai School of Medicine, New York, NY, USA.
Geller
Jordan L
JL
Vasiliauskas
Eric A
EA
Kam
Lori Y
LY
Vora
Puja
P
Martyak
Lenna A
LA
Yang
Huiying
H
Hu
Bei
B
Lin
Ying-Chao
YC
Keenan
Gregory
G
Price
Joanne
J
Landers
Carol J
CJ
Adams
John S
JS
Targan
Stephan R
SR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D016207:Cytokines; D005765:Gastrointestinal Agents; D010281:Parathyroid Hormone; D000069285:Infliximab; D000469:Alkaline Phosphatase; D002118:Calcium