Inflammation and glucocorticoid therapy impair skeletal modeling during growth following crohn disease diagnosis

Anne Tsampalieros; Justine Shults; Babette Zemel; Robert Baldassano; Mary Leonard

doi:10.1530/boneabs.2.OP14

Objectives: Examine changes in volumetric BMD and cortical structure following Crohn Disease (CD) diagnosis, and identify associations with growth, glucocorticoid exposure and disease activity.

Methods: Prospective cohort study in 76 CD participants, ages 5–21 years. Tibia pQCT scans were obtained at diagnosis, 6, 12 and a median of 42 months later. Sex, race and age-specific Z-scores were generated based on >650 controls. Cortical dimension Z-scores were adjusted for tibia length-for-age Z-score. Generalized estimating equations were used to identify correlates of changes in Z-scores.

Results: Disease activity improved markedly over the study interval (Table 1). Trabecular BMD Z-scores increased significantly: improvements were greater over the first 6 months and in younger children (P=0.005), and were associated with improvements in disease activity (P<0.001). Cortical BMD Z-scores decreased significantly: greater increases in tibia length were associated with greater increases in cortical area Z-scores and declines (improvements) in endosteal circumference Z-scores (both P<0.001). Increases in cortical area Z-scores were associated with declines in cortical BMD Z-scores (P<0.001). Greater glucocorticoid doses and disease activity were significantly associated with lesser gains in cortical area, and these associations were more pronounced with greater linear growth (interaction P<0.05). Despite minimal disease activity at the final visit, trabecular and cortical BMD and cortical area Z-scores were significantly reduced, compared with controls (all P<0.001).

Table 1 Results at baseline and LTFU.
	Baseline	LTFU	P value
Pediatric CD activity index, n (%)			< 0.001
No active disease (≤ 10)	1 (2)	41 (85)
Mild (11–30)	14 (29)	7(15)
Moderate to severe (>30)	33 (69)	0 (0)
Trabecular BMD-Z	−1.47±1.19*	−1.01±1.21*	0.0001
Cortical BMD-Z	−0.25±1.06	−1.06±1.06*	<0.0001
Cortical area-Z	−0.83±1.18*	−0.57±1.10*	0.03
Periosteal circumference-Z	−0.22±0.92	−0.22±0.83	0.98
Endosteal circumference-Z	0.60±0.91*	0.38±0.92*	0.004
*P<0.05 compared to reference participants. Table limited to the 51 that completed the LTFU visit. Z-scores presented as mean ± S.D.

Conclusions: These data suggest glucocorticoids and inflammatory disease activity independently impair cortical bone accrual relative to increases in tibia length, reflecting the unique vulnerability of the growing skeleton. In contrast, the greater improvements in trabecular BMD in younger participants, and the positive association between growth and accrual of cortical dimensions suggest a window of opportunity for recovery in the absence of significant glucocorticoid exposure and disease activity.

Bone Abstracts

OP14