Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn's disease: results of the REACH study.
OBJECTIVE
Crohn's disease (CD) is associated with altered bone metabolism. This study examined changes in bone formation and resorption after infliximab induction and associations between bone biomarkers, linear growth, and disease activity (Pediatric Crohn's Disease Activity Index [PCDAI]) after 54 weeks of infliximab therapy.


METHODS
One hundred twelve subjects ages 6-17 years with moderate to severe CD received infliximab induction (5 mg/kg/dose) at weeks 0, 2, and 6; week-10 responders were randomized to infliximab every 8 or every 12 weeks maintenance therapy. Serum bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), urine C-telopeptide of collagen cross-links (CTX-1), and deoxypyrodinoline (DPD) were collected at baseline and 10 weeks. PCDAI and height z-scores were assessed at baseline and at 10 and 54 weeks.


RESULTS
Models were adjusted for bone age, gender, height, and steroid use. Baseline BSAP and P1NP levels were negatively associated with PCDAI (both P = .01). BSAP and P1NP increased during induction (both P < .001) and were associated with 54-week increases in height z-score (P < .05 and P < .001, respectively). Improvements in P1NP were associated with 54-week decreases in PCDAI (P = .01). CTX-1 and DPD also increased during induction (P < .001 and P = .01, respectively) but were not associated with changes in PCDAI. Changes in CTX-1 were associated with improvements in height z-score (P < .002).


CONCLUSIONS
Infliximab therapy is associated with dramatic increases in BSAP and P1NP, consistent with inhibition of tumor necrosis factor-alpha effects on osteoblasts. The increases in CTX-1 and DPD likely reflect coupling of bone formation and resorption and increases in linear growth.
Thayu
Meena
M
Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19014, USA. thayu@email.chop.edu
Leonard
Mary B
MB
Hyams
Jeffrey S
JS
Crandall
Wallace V
WV
Kugathasan
Subra
S
Otley
Anthony R
AR
Olson
Allan
A
Johanns
Jewel
J
Marano
Colleen W
CW
Heuschkel
Robert B
RB
Veereman-Wauters
Gigi
G
Griffiths
Anne M
AM
Baldassano
Robert N
RN
D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D024042:Collagen Type I / Q000097:blood / Q000652:urine; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D010455:Peptides / Q000652:urine; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D007155:Immunologic Factors; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000069285:Infliximab; D000469:Alkaline Phosphatase