Gastrointestinal (GI) diseases such as inflammatory bowel disease (IBD), malabsorption syndromes including celiac disease, and postgastrectomy state in gastric cancer survivors are related to high rates of osteopenia and osteoporosis in adults [1,2]. According to a recent report, osteoporosis was found in 32%–42% of postgastrectomy, 18%–42% of IBD, and 15%–22% of celiac disease patients [1,2]. Further, the risk of fracture was also relatively high in adult patients with these GI diseases [1,2].

Similarly, some chronic GI diseases including IBD; rare malabsorption syndromes such as cystic fibrosis, intestinal lymphangiectasia, congenital chloride diarrhea, and celiac disease; and postsubtotal gastrectomy state or short-bowel syndrome after extensive bowel resection have been linked with osteopenia and osteoporosis in pediatric patients. However, data on poor bone health status in pediatric GI diseases remain limited.

This review article sought to provide updates on bone health issues in pediatric GI diseases using the most recent evidence.

Malabsorption syndromes such as primary intestinal lymphangiectasia (PIL), celiac disease, congenital chloride diarrhea, and cystic fibrosis are rare in children [1,2].

PIL is a common etiology of protein-losing enteropathy characterized by abnormally dilated lymphatic ducts in the intestinal wall [15]. Because PIL affects the absorption of lipid-soluble vitamins, electrolytes, and minerals, malnutrition (vitamin D and calcium deficiency) related to osteomalacia and osteoporosis can develop in children with PIL [15]. There have been several case reports of low BMD with increased serum levels of parathyroid hormone and vitamin D in PIL, all of which were efficaciously treated with adequate calcium and vitamin D supplementation [15,16].

Celiac disease, i.e., gluten-sensitive enteropathy, is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and characterized by the presence of a variable combination of gluten-dependent clinical manifestations; celiac disease-specific antibodies such as anti-transglutaminase 2, antiendomysial antibody, gliadin, HLA-DQ2, or DQ8 haplotypes; and enteropathy with symptoms and signs of malabsorption [17].

Osteoporosis with hypocalcemia and hypocalciuria occurs as one of the extraintestinal manifestations in children with celiac disease [17]. To date, some severe cases of spontaneous bone fracture have been reported. Poor bone health in celiac disease is related to chronic malabsorption of calcium and vitamin D.

In the screening and prevention of abnormal bone health, a recent guideline by the British Society of Gastroenterology recommended measurement of calcium, alkaline phosphatase, and vitamin D level in serum, with parathyroid hormone and calcium intake maintained at or above 1,000 mg/day [17]. This guideline also supported continued measurement of BMD by DXA at intervals of 2 years in patients with ongoing villous atrophy, poor dietary adherence, and low BMD [17]. Elsewhere, a recent position paper recommended adult patients with celiac disease undergo serum calcium, albumin, 25(OH) vitamin D parathyroid hormone, and 24-hour urine calcium testing at the time of diagnosis as well as DXA imaging in those at risk for osteoporosis, which should be repeated one to 2 years after initiation of a gluten-free diet [18]. Another guideline by the American Gastroenterology Association recommended that DXA scan be performed at one year after initiating a gluten-free diet in adults with celiac disease [19].

A study on bone health status in 74 children with celiac disease revealed that 16% of newly diagnosed celiac disease cases had BMD z-score less than -2, although there were no differences in BMD z-score between symptomatic and asymptomatic children [20]. In addition, age at diagnosis was inversely correlated with BMD z-score, and delayed diagnosis in children with celiac disease increased the risk of osteoporosis [20]. In pediatric patients with celiac disease, low BMD can be reversed by adherence to a gluten-free diet with restoration of normal peak BMD. Therefore, early routine evaluation for BMD using DXA and early nutritional intervention are recommended in children with celiac disease to assure better outcomes. A recent position paper recommended DXA scanning one year after diagnosis if gluten-free diet adherence is not strict [18].

Short-bowel syndrome is an intestinal dysfunction, and complications following extensive loss of the small bowel can result in insufficient nutrient absorption and requirement for parenteral nutritional support. In clinical practice, extensive resection of the intestine in cases of necrotizing enterocolitis, intestinal atresia, volvulus, or gastroschisis is a primary cause of short-bowel syndrome. In children with short-bowel syndrome, prognosis factors include the length of the remnant bowel, bowel condition, preservation of the ileocecal valve, and stomy formation [21]. Usually, a total small-bowel length less than 40-cm necessitates more than 2 years of adaptation by the remnant bowel.

Malabsorption after extensive bowel resection results in fluid and electrolyte abnormalities and malnutrition in children. Metabolic changes due to loss of colonic regulation of gastric and small-bowel function lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and low BMD [21]. Parenteral nutrition, persistent inflammation, steroid use, chronic metabolic acidosis, and renal insufficiency are additional factors that contribute to development of bone disease in patients with short-bowel syndrome [21].

According to a retrospective study of 36 pediatric intestinal failure patients on parenteral nutrition for more than 30 days, BMD z-score less than -1.0 on DXA scanning was noted in 50% (n=18) of the patients, serum 25(OH) vitamin D level less than 30 ng/mL was found in 63.8%, and pathologic fracture was observed in 11.1% (n=4) [22]. In this pediatric study, duration of parenteral nutrition was significantly associated with low BMD [22]. In another retrospective study of 123 intestinal failure patients both children and young adults on total parenteral nutrition for more than 30 days, BMD z-score less than -2.0 was noted in 12.5% (n=18), and serum 25(OH) vitamin D level less than 20 ng/mL was recorded in 39.8% (n=49). In this pediatric study, duration of parenteral nutrition was significantly associated with low BMD [23].

Therefore, appropriate strategies for monitoring and preventing abnormal bone health are needed to secure better outcomes in children with short-bowel syndrome and intestinal failure receiving long-term parenteral nutrition.

Examples of abnormal bone health, including low BMD, osteopenia or osteoporosis, and fracture, are common complications of pediatric GI diseases. The pathophysiology of bone abnormality may be different according to disease entity, ranging from chronic inflammation to malabsorption and malnutrition. Regardless of underlying conditions, routine evaluation of bone health status using DXA and appropriate prevention or treatment strategies are needed in children with chronic GI diseases at high risk, especially in those with IBD, malabsorption syndrome, or short-bowel syndrome.