Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease

Background: In children with inflammatory bowel disease (IBD) it is not known whether reductions in bone mineral density (BMD) are a consequence of bone turnover alterations and if BMD improves with treatment. Methods: In a cohort of children with IBD, we prospectively measured indicators of bone remodeling, body mass index (BMI), disease activity, intact parathyroid hormone, serum IL‐6, and insulin‐like growth factor‐I at diagnosis and then every 6 months for 2 years. BMD was determined annually using dual x‐ray absorptiometry (DXA). BMD Z‐scores were calculated using height/age. Baseline measurements and calcium intake were compared with a group of age‐ and sex‐matched healthy children. Results: We observed that at diagnosis total body BMD Z‐score (mean ± SD) was −0.78 ± 1.02 for Crohn's disease (CD, n = 58), −0.46 ± 1.14 for ulcerative colitis (UC, n = 18), and −0.17 ± 0.95 for control (CL, n = 49) (P < 0.01, CD versus CL). In CD, a BMD Z‐score <−1.0 was associated with lower BMI and higher serum IL‐6. Patients with CD and UC had low bone turnover. Activation of bone formation paralleled clinical improvement, but BMC gain was less than expected over the 2‐year study period, especially in CD. Prednisone use did not correlate with low BMD. Conclusions: Decreased bone turnover occurs in children newly diagnosed with IBD. Although indicators of osteoblast activity increase with clinical improvement, bone mineral accrual does not accelerate. Children with low BMI may be considered for BMD screening, since they are at risk for low bone mass.

[1]  M. Drezner,et al.  HPLC method for 25-hydroxyvitamin D measurement: comparison with contemporary assays. , 2006, Clinical chemistry.

[2]  J. Stains,et al.  Cell-to-cell interactions in bone. , 2005, Biochemical and biophysical research communications.

[3]  D. Hanley,et al.  Vitamin D insufficiency in North America. , 2005, The Journal of nutrition.

[4]  J. Burnham,et al.  Whole Body BMC in Pediatric Crohn Disease: Independent Effects of Altered Growth, Maturation, and Body Composition , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  F. Muntoni,et al.  The relationship between lean body mass and bone mineral content in paediatric health and disease. , 2004, Bone.

[6]  D. Rachmilewitz,et al.  Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones. , 2004, Gastroenterology.

[7]  Shirley C. Paski,et al.  Lumbar spine bone mineral density at diagnosis and during follow-up in children with IBD. , 2004, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[8]  D. Bailey,et al.  The 'muscle-bone unit' during the pubertal growth spurt. , 2004, Bone.

[9]  S. Ahmed,et al.  Bone Mineral Assessment by Dual Energy X-ray Absorptiometry in Children With Inflammatory Bowel Disease: Evaluation by Age or Bone Area , 2004, Journal of pediatric gastroenterology and nutrition.

[10]  J. Baron,et al.  Overdiagnosis of osteoporosis in children due to misinterpretation of dual-energy x-ray absorptiometry (DEXA). , 2004, The Journal of pediatrics.

[11]  W. Leslie,et al.  AGA technical review on osteoporosis in gastrointestinal diseases. , 2003, Gastroenterology.

[12]  A. Griffiths,et al.  Effects of Serum From Children with Newly Diagnosed Crohn Disease on Primary Cultures of Rat Osteoblasts , 2002, Journal of pediatric gastroenterology and nutrition.

[13]  B. Zemel,et al.  Vitamin D status in children, adolescents, and young adults with Crohn disease. , 2002, The American journal of clinical nutrition.

[14]  D. Felsenberg,et al.  High prevalence of osteoporotic vertebral fractures in patients with Crohn’s disease , 2002, Gut.

[15]  E P Krenning,et al.  Reference data for bone density and body composition measured with dual energy x ray absorptiometry in white children and young adults , 2002, Archives of disease in childhood.

[16]  D. Felsenberg,et al.  Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease , 2002, Alimentary pharmacology & therapeutics.

[17]  L. Melton,et al.  Long-term fracture risk in patients with Crohn's disease: a population-based study in Olmsted County, Minnesota. , 2002, Gastroenterology.

[18]  J. Compston Can biochemical markers be used to screen patients with inflammatory bowel disease for osteoporosis? , 2002, European journal of gastroenterology & hepatology.

[19]  S. Abrams,et al.  Z Score Prediction Model for Assessment of Bone Mineral Content in Pediatric Diseases * , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  Susan R. Johnson,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2001, JAMA.

[21]  E. Schoon,et al.  Bone mineral density in patients with recently diagnosed inflammatory bowel disease. , 2000, Gastroenterology.

[22]  S. Laurberg,et al.  Fracture risk is increased in Crohn's disease, but not in ulcerative colitis , 2000, Gut.

[23]  G. Porro,et al.  Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn’s disease and ulcerative colitis , 2000, Journal of internal medicine.

[24]  F. Glorieux,et al.  Interpretation of Bone Mineral Density Values in Pediatric Crohn's Disease , 1998, Inflammatory bowel diseases.

[25]  K. Mann,et al.  Reduced Bone Mineral Density and Unbalanced Bone Metabolism in Patients with Inflammatory Bowel Disease , 1998, Inflammatory bowel diseases.

[26]  B. Kirschner,et al.  Bone mineral density assessment in children with inflammatory bowel disease. , 1998, Gastroenterology.

[27]  A. Jawad,et al.  EFFECT OF SITE OF DISEASE AND STEROID EXPOSURE ON BONE MINERAL DENSITY (BMD) IN CHILDREN WITH CROHN'S DISEASE: 35 , 1997 .

[28]  R. Baldassano,et al.  AZATHIOPRINE AND 6-MERCAPTOPURINE IN THE TREATMENT OF SEVERE PERIANAL CROHN'S DISEASE IN CHILDREN: 38 , 1997 .

[29]  V. Stallings,et al.  Vertebral compression fractures in pediatric patients with Crohn's disease. , 1997, Gastroenterology.

[30]  J. Hyams,et al.  Alterations in bone metabolism in children with inflammatory bowel disease: an in vitro study. , 1997, Journal of pediatric gastroenterology and nutrition.

[31]  I. Forgacs,et al.  Reduced bone density in patients with inflammatory bowel disease. , 1997, Gut.

[32]  J. Chow,et al.  Colitis causes bone loss in rats through suppression of bone formation. , 1996, Gastroenterology.

[33]  S. Atkinson,et al.  Longitudinal Assessment of Growth, Mineral Metabolism, and Bone Mass in Pediatric Crohn's Disease , 1993, Journal of pediatric gastroenterology and nutrition.

[34]  P. Croucher,et al.  Reduced bone formation in patients with osteoporosis associated with inflammatory bowel disease , 1993, Osteoporosis International.

[35]  J. Hyams,et al.  Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease. , 1993, Gastroenterology.

[36]  J T Boyle,et al.  Development and validation of a pediatric Crohn's disease activity index. , 1991, Journal of pediatric gastroenterology and nutrition.

[37]  I. Rosenberg,et al.  Vitamin D deficiency and bone disease in patients with Crohn's disease. , 1982, Gastroenterology.

[38]  S. Truelove,et al.  Cortisone in Ulcerative Colitis , 1954 .

[39]  M. Maresh,et al.  Radiographic Atlas of Skeletal Development of the Hand and Wrist , 1950 .

[40]  W. Cooke Vitamin D deficiency and bone disease in patients with Crohn's disease. , 1983, Gastroenterology.

[41]  S. Truelove,et al.  Cortisone in ulcerative colitis; final report on a therapeutic trial. , 1955, British medical journal.

[42]  E. Krenning,et al.  Bone mineral density and nutritional status in children with chronic inflammatory bowel disease , 1998, Gut.