Bone Deficits in Parenteral Nutrition–Dependent Infants and Children With Intestinal Failure Are Attenuated When Accounting for Slower Growth

Abstract

Objective To determine if bone mineral content (BMC) and density (BMD) of infants and children with parenteral nutrition (PN)-dependent intestinal failure (IF) is lower than healthy controls, and investigate potential causes of lower BMC and BMD. Methods We performed a cross-sectional study comparing infants and children with PN-dependent IF with duos of age, sex, and race matched controls. Lumbar spine BMC and BMD were measured by dual energy x-ray absorptiometry, and serum cytokines, aluminum, IGF-1, insulin-like growth factor-binding protein (IGF-BP)-3, parathyroid hormone, 25(OH) vitamin D, and 1,25(OH)2 vitamin D were measured. Generalized estimating equation models accounting for matching were used for comparisons. Results BMC was 15% and BMD was 12% lower in IF participants than controls (p≤0.004). Group differences were attenuated to 3% and 7% and were not statistically significant (p=0.40 and p=0.07) when adjusted for length and weight; length- and weight-for-age were lower in IF than control participants (12.5% vs. 63%; 29.5% vs. 54%, p≤0.03). IF participants had higher serum aluminum (23 vs. 7 mcg/L, p<0.0001), IGF-1 (97 vs. 64 ng/mL, p=0.04), and 25(OH) vitamin D concentrations (40 vs. 30 ng/mL, p=0.0005), and lower IGF-BP3 (1418 vs. 1812 ng/mL, p<0.0001) and parathyroid hormone concentrations (51 vs. 98 pg/mL, p=0.0002) than controls. There was no difference in serum cytokine concentrations (p≥0.09). Conclusions Growth retardation is a significant problem for PN-dependent IF patients. Additional investigation is needed to elucidate the cause and its impact on bone mass and density, especially the role of IGF-1 resistance and aluminum toxicity.

Bone mineral density and vitamin D in paediatric intestinal failure patients receiving home parenteral nutrition

“…2). This is different from another study of paediatric IF patients on PN where a normal value of 1,25(OH)2D was found [43]. Lower 1,25(OH) 2 D level raises questions regarding the mechanism.…”

“…However, no difference was found for healthy participants included during MarcheJune compared to AugusteSeptember. Other studies have reported vitamin D insufficiency in 20e68% of paediatric IF patients [12,13,33,34,36,37,41,42], which is more than the 5% found by Appleman et al [43], and the 10% found in the present study. An explanation could be that these studies also included patients weaned off PN, and hence their absorption could be compromised.…”

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Organisational aspects

“…For patients who are PN dependent long term, body composition is often abnormal with significant deficit in limb lean mass [62]. Metabolic bone disease is related to aluminium contaminating fluids, low serum vitamin D and insulin-like growth factor, and inflammation [63]. Bone mineral density is reduced particularly in children with congenital enterocyte disorders or severe dysmotility [64].…”

Body Composition Using Air Displacement Plethysmography in Children With Intestinal Failure Receiving Long‐Term Home Parenteral Nutrition

“…Previous studies reported that children with IF are significantly lighter and shorter than healthy chidren. [2][3][4][5] One study assessing body composition showed that they have a lower FFM. 3 In addition, fully PN-dependent patients had increased FM.…”