Maintenance of optimal vitamin D status in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing two regimens.

CONTEXT: Vitamin D promotes bone health and regulates the immune system, both important actions for pediatric patients with inflammatory bowel disease (IBD). The supplementation dose that would maintain optimal serum 25-hydroxyvitamin D concentration (25OHD ≥ 32 ng/mL) is unknown. OBJECTIVE: The objective of the study was to compare two supplementation regimens' efficacy and safety in maintaining optimal 25OHD in children with IBD. DESIGN: This was a randomized, not blinded, controlled trial. SETTING: The trial was conducted in the Boston Children's Hospital Clinical and Translational Study Unit. PARTICIPANTS: Sixty-three patients, aged 8-18 years with IBD and baseline 25OHD greater than 20 ng/mL were enrolled; 48 completed the study, and one withdrew for adverse events. INTERVENTION: Arm A received 400 IU of oral vitamin D2 daily (n = 32). Arm B received 1000 IU daily in the summer/fall and 2000 IU in the winter/spring (n = 31). MAIN OUTCOME: The main outcome was the probability of maintaining 25OHD of 32 ng/mL or greater in all trimonthly visits for 12 months. RESULTS: Three participants in arm A (9.4%) and three in arm B (9.7%) achieved the primary outcome (P = .97). The incidence of adverse events, all minor, did not differ. More participants in arm A developed C-reactive protein level of 1 mg/dL or greater (31% vs 10%, P = .04) and IL-6 greater than 3 pg/mL (54% vs 27%, P = .05). CONCLUSIONS: Daily oral vitamin D2 doses up to 2000 IU were inadequate to maintain optimal 25OHD but were well tolerated. The finding of lower incidence of elevated inflammatory markers and cytokines among participants receiving higher vitamin D2 doses merits further study.

Treatment of vitamin D insufficiency in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing three regimens.

CONTEXT: Vitamin D insufficiency [serum 25-hydroxyvitamin D (25OHD) concentration less than 20 ng/ml] is prevalent among children with inflammatory bowel disease (IBD), and its treatment has not been studied. OBJECTIVE: The aim of this study was to compare the efficacy and safety of three vitamin D repletion regimens. DESIGN AND SETTING: We conducted a randomized, controlled clinical trial from November 2007 to June 2010 at the Clinical and Translational Study Unit of Children's Hospital Boston. The study was not blinded to participants and investigators. PATIENTS: Eligibility criteria included diagnosis of IBD, age 5-21, and serum 25OHD concentration below 20 ng/ml. Seventy-one patients enrolled, 61 completed the trial, and two withdrew due to adverse events. INTERVENTION: Patients received orally for 6 wk: vitamin D(2), 2,000 IU daily (arm A, control); vitamin D(3), 2,000 IU daily (arm B); vitamin D(2), 50,000 IU weekly (arm C); and an age-appropriate calcium supplement. MAIN OUTCOME MEASURE: We measured the change in serum 25OHD concentration (Δ25OHD) (ng/ml). Secondary outcomes included change in serum intact PTH concentration (ΔPTH) (pg/ml) and the adverse event occurrence rate. RESULTS: After 6 wk, Δ25OHD ± se was: 9.3 ± 1.8 (arm A); 16.4 ± 2.0 (arm B); 25.4 ± 2.5 (arm C); P (A vs. C) = 0.0004; P (A vs. B) = 0.03. ΔPTH ± SE was -5.6 ± 5.5 (arm A); -0.1 ± 4.2 (arm B); -4.4 ± 3.9 (arm C); P = 0.57. No participant experienced hypercalcemia or hyperphosphatemia, and the prevalence of hypercalciuria did not differ among arms at follow-up. CONCLUSIONS: Oral doses of 2,000 IU vitamin D(3) daily and 50,000 IU vitamin D(2) weekly for 6 wk are superior to 2,000 IU vitamin D(2) daily for 6 wk in raising serum 25OHD concentration and are well-tolerated among children and adolescents with IBD. The change in serum PTH concentration did not differ among arms.

Efficacy and harms of nasal calcitonin in improving bone density in young patients with inflammatory bowel disease: a randomized, placebo-controlled, double-blind trial.

OBJECTIVES: There are very few published studies of agents having the potential to improve bone health in children with inflammatory bowel disease (IBD). The objective of this study was to establish the efficacy and safety of intranasal calcitonin in improving bone mineral density (BMD) in young patients with IBD and to define additional factors that impact bone mineral accrual. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial in 63 participants, ages 8-21 years, with a spinal BMD Z-score ≤ -1.0 s.d. measured by dual energy X-ray absorptiometry. Subjects were randomized to 200 IU intranasal calcitonin (n=31) or placebo (n=32) daily. All received age-appropriate calcium and vitamin D supplementation. Subsequent BMD measurements were obtained at 9 and 18 months. RESULTS: Intranasal calcitonin was well tolerated. Adverse event frequency was similar in both treatment groups, and such events were primarily minor, reversible, and limited to the upper respiratory tract. The BMD Z-score change documented at screening and 9 months and screening and 18 months did not differ between the two therapeutic arms. In participants with Crohn's disease, the spinal BMD Z-score improved between screening and 9 months (change in spine BMD Z-score (ΔZSBMD)(9-0)) in the calcitonin group (ΔZSBMD(9-0)(calcitonin)=0.21 (0.37), ΔZSBMD(9-0)(placebo)=-0.15 (0.5), P=0.02); however, this was only a secondary subgroup analysis. Bone mineral accrual rate during the trial did not lead to normalization of BMD Z-score in this cohort. Factors favoring higher bone mineral accrual rate were lower baseline BMD and higher baseline body mass index Z-score, improvement in height Z-score, higher serum albumin, hematocrit and iron concentration, and more hours of weekly weight-bearing activity. Factors associated with lower bone mineral accrual rate were more severe disease-as indicated by elevated inflammatory markers, need for surgery, hospitalization, and the use of immunomodulators-and higher daily caffeine intake. CONCLUSIONS: Intranasal calcitonin is well tolerated but does not offer a long-term advantage in youth with IBD and decreased BMD. Bone mineral accrual rate remains compromised in youth with IBD and low BMD raising concerns for long-term bone health outcomes. Improvement in nutritional status, catch-up linear growth, control of inflammation, increase in weight-bearing activity, and lower daily caffeine intake may be helpful in restoring bone density in children with IBD and low BMD.

Vitamin D status in gastrointestinal and liver disease.

PURPOSE OF REVIEW: The purpose of this review is to report on the vitamin D status and its relationship with bone health in individuals with gastrointestinal and liver disorders. In addition, recommendations regarding replacement and maintenance of optimal vitamin D stores, as well as the state of knowledge regarding its effect on the disease through its actions on the immune system, will be reviewed. RECENT FINDINGS: The scientific community has revised upward the serum levels of vitamin D considered optimal, and doses of vitamin D much larger than those currently recommended may be needed to maintain these levels, especially in individuals with gastrointestinal and liver disorders. The relationship between vitamin D and bone health in this population is controversial. The role of vitamin D in the regulation of the immune system continues to be elucidated. SUMMARY: Hypovitaminosis D is prevalent among individuals with gastrointestinal and liver disease. Although replacement and supplementation guidelines have not been well defined, practitioners should aim for a serum 25-hydroxyvitamin D level of at least 32 ng/ml. The contribution of vitamin D to the bone health of these individuals and its role in altering disease course through its actions on the immune system remain to be elucidated.

Vitamin D status in children and young adults with inflammatory bowel disease.

OBJECTIVES: Previous studies of vitamin D status in pediatric patients with inflammatory bowel disease have revealed conflicting results. We sought to report (1) the prevalence of vitamin D deficiency (serum 25-hydroxy-vitamin D concentration < or = 15 ng/mL) in a large population with inflammatory bowel disease, (2) factors predisposing to this problem, and (3) its relationship to bone health and serum parathyroid hormone concentration. PATIENTS AND METHODS: A total of 130 patients (8-22 years of age) with inflammatory bowel disease, 94 with Crohn disease and 36 with ulcerative colitis, had serum 25-hydroxy-vitamin D, intact parathyroid hormone, and lumbar spine bone mineral density (using dual-energy x-ray absorptiometry) measured at Children's Hospital Boston. RESULTS: The prevalence of vitamin D deficiency was 34.6%. Mean serum 25-hydroxy-vitamin D concentration was similar in patients with Crohn disease and ulcerative colitis, 52.6% lower among patients with dark skin complexion, 33.4% lower during the winter months (December 22 to March 21), and 31.5% higher among patients who were taking vitamin D supplements. Serum 25-hydroxy-vitamin D concentration was positively correlated with weight and BMI z score, disease duration, and serum albumin concentration and negatively correlated with erythrocyte sedimentation rate. Patients with Crohn disease and upper gastrointestinal tract involvement were more likely to be vitamin D deficient than those without it. Serum 25-hydroxy-vitamin concentration was not associated with lumbar spine bone mineral density z score or serum parathyroid hormone concentration. CONCLUSIONS: Vitamin D deficiency is highly prevalent among pediatric patients with inflammatory bowel disease. Factors predisposing to the problem include having a dark-skin complexion, winter season, lack of vitamin D supplementation, early stage of disease, more severe disease, and upper gastrointestinal tract involvement in patients with Crohn disease. The long-term significance of hypovitaminosis D for this population is unknown at present and merits additional study.