Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease

Abstract

Context: Pediatric Crohn's Disease (CD) is associated with deficits in trabecular bone mineral density (BMD) and cortical structure, potentially related to TNF-α effects to decrease bone formation and promote bone resorption.

Objective: This study aimed to examine changes in bone density and structure in children and adolescents with CD following initiation of anti-TNF-α therapy.

Design and participants: Participants (n = 74; age 5-21 years) with CD completed a 12-month prospective cohort study.

Main outcome measures: Tibia peripheral quantitative computed tomography scans were obtained at initiation of anti-TNF-α therapy and 12 months later. Musculoskeletal outcomes were expressed as sex-and race-specific z scores relative to age, based on >650 reference participants.

Results: At baseline, CD participants had lower height, trabecular BMD, cortical area (due to smaller periosteal and larger endocortical circumferences), and muscle area z scores, compared with reference participants (all P < .01). Pediatric CD activity index decreased during the 10-week induction (P < .001), in association with subsequent gains in height, trabecular BMD, cortical area (due to recovery of endocortical bone), and muscle area z scores over 12 months (height P < .05; others P < .001). Bone-specific alkaline phosphatase levels, a biomarker of bone formation, increased a median of 75% (P < .001) during induction with associated 12-month improvements in trabecular BMD and cortical area z scores (both P < .001). Younger age was associated with greater increases in trabecular BMD z scores (P < .001) and greater linear growth with greater recovery of cortical area (P < .001).

Conclusions: Anti-TNF-α therapy was associated with improvements in trabecular BMD and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits.

Figure 1.

PCDAI scores and trabecular BMD and corical area z scores following initiation of infliximab therapy. Greater declines in PCDAI scores over the first 10 weeks were significantly associated with greater gains in trabecular BMD and cortical area z scores over the 12-month study. The dashed lines represent the median z scores in the reference participants.

Figure 2.

Associations between changes in cortical z scores and changes in tibia length. Only change in periosteal circumference was not significantly associated with change in tibia length (P = .86). The associations shown below remained significant in models adjusted for baseline cortical z score.

Figure 3.

Change in trabecular BMD and endocortical circumference in a 14-year-old male participant with a decrease in PCDAI from 45 to 0 and an increase in tibia length from 328 to 339 mm over the 12-month interval. The endocortical circumference decreased from 37 (A) to 35 (B) mm, corresponding with an improvement in z score from 1.35 to 0.85. Trabecular BMD increased from 174 (C) to 213 (D) gm/cm³, corresponding with an increase in trabecular BMD z score from −2.72 to −1.44.