Bone Density in Children With IBD Treated With Amorphous Calcium or Commercial Crystalline Calcium: A Prospective Randomized Multicenter Trial

Abstract- Scientific Background Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative Colitis (UC) are chronic disorders of the gastrointestinal tract defined by relapsing and remitting episodes. One of the concerning comorbidities of IBD is reduced bone mineral density (BMD). Recent studies have reported that 43%-46% of children with CD had BMD z-scores <_1 SD at diagnosis (1.2) and that BMD did not improve during treatment for IBD. Chronic inflammation has an adverse effect on skeletal muscle health in children with IBD by multiple mechanisms. Emerging data suggests an increased risk of vertebral fractures in these patients (3). In longitudinal studies, Children with IBD had significantly lower mean BMD z scores for the lumbar spine (LS) at baseline and after 2 years. The reduction occurred in UC and CD, and neither improved their z score during follow-up (4).

Patients diagnosed with, or in risk of osteoporosis regularly take calcium dietary supplements, although their contribution to BMD maintenance, prevention of bone loss or reduction of the risk of fracture is questionable. Freshwater crayfish rely on amorphous calcium carbonate (ACC), a thermodynamically instable and very rare biomineralized polymorph of calcium carbonate, as the main mineral in the exoskeleton and in their temporary storage organ, the gastrolith. Preclinical studies revealed an increase in calcium gastrointestinal bioavailability, bone absorption and retention in rats administered with ACC compared to other calcium supplementation. ACC's beneficial effects on bone loss prevention, bone formation and bone mechanical strength maintenance, was also demonstrated in an ovaryectomy rat model. A clinical study conducted by on 13 postmenopausal women revealed a 2 fold increase in calcium gastrointestinal bioavailability from ACC compared with Calcium Carbonate (5,6). α-Klotho (klotho) is a transmembrane protein which can be cleaved and shed to act as a circulating hormone (7), and is an essential cofactor for the binding of fibroblast growth factor (FGF) to its cognate receptor, serving as a major regulator of phosphate homeostasis (8). Low klotho levels were recently noted in adolescents with anorexia nervosa (9).

Hypothesis

1. Amorphous calcium carbonate (ACC) will have an advantage over calcium carbonate in improving BMD of pediatric IBD patients with reduced BMD.
2. Serum klotho levels will be reduced at the time of IBD diagnosis and will increase following weight rehabilitation. Furthermore, klotho levels will be associated with bone density and with the activity of the GH/IGF-1 axis.

Study Aims