1. How Should We Monitor, Prevent, and Treat Osteoporosis in IBD? All of Our IBD Patients are at Risk and Therefore all Should Begin Treatment at Diagnosis Ted Denson, MD Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine

2. Disclosures Grant support: NIH & CCFA

3. Bone Health in Children with IBD Bone mineral density (BMD) is often reduced in children with IBD Low trauma and vertebral compression fractures can occur Does low BMD predict future fractures in children with IBD? Does DXA measurement of BMD predict future fractures in children with IBD? How does DXA measurement of low BMD affect clinical management? Sylvester, Inflamm Bowel Dis 2005; 11:1020-3

4. Screening for Risk of Fractures Goal of noninvasive skeletal testing is to identify children at risk for low trauma fractures; fracture threshold not well defined Bachrach, Endocrinol Metab Clin North Am 2005; 34:521-35

5. Which IBD Patients Should Have DXA Performed? Pappa et al, JPGN 2012 “All children with IBD who can lie on a cushioned table for 15 to 20 minutes should have a DXA scan.” “Therapeutic interventions should not be instituted on the basis of a single DXA measurement.”

6. Limitations of DXA Bone resistance to fracture: bone mass, geometry, quality, and material properties DXA does not measure volumetric bone mineral density; estimated from 2D measurement DXA does not measure bone geometry DXA does not distinguish between cortical and trabecular bone QCT and pQCT capture these measures but are limited by cost, radiation, and normative values Bachrach, Endocrinol Metab Clin North Am 2005; 34:521-35

7. DXA Overestimates Low BMD Compared to QCT Wren et al, J Peds 2005 “The inability of DXA to to account for the large variability in skeletal size and body composition in growing children greatly diminishes the accuracy in the pediatric population ”

8. Pitfalls in the DXA Interpretation PA lumbar spine preferred site Always use age & gender Z-score & pediatric norms, never T-score (reflects adult peak bone mass) DXA underestimates vBMD in children with reduced height for age Need to account for height Z-score and delayed bone age A Z-score < -2 = “low bone mineral density for age”, not osteoporosis A low Z-score by itself should not be a reason to start anti- resorptive (bisphosphonate) treatment; low trauma fracture a better indication Bachrach, Endocrinol Metab Clin North Am 2005; 34:521-35

9. Accounting for Delayed Bone Age in DXA Bachrach, Endocrinol Metab Clin North Am 2005; 34:521-35

10. DXA Results and Risk of Fracture Clark et al, JBMR 2006 6213 healthy children with DXA at age 9.9 followed for two years 550 (8.9%) with at least one fracture “Weak inverse relationship between BMD at 9.9 years and subsequent fracture risk: OR per SD decrease: 1.12(1.02-1.25)”

11. Most Adult CD Patients with Vertebral Fractures have Normal BMD Siffledeen et al, Clin Gastro Hep 2007

12. Inflammatory Markers and PTH are Associated with Vertebral Compression Fractures in Adult CD Siffledeen et al, Clin Gastro Hep 2007 “BMD screening on its own is not sufficient to predict the onset of metabolic bone disease in this population” “Hypothesis: inflammation induces microarchitectural changes in trabecular bone”

13. Effective IBD Therapy Addresses the Pathogenesis of Bone Disease Bone resorption Faster Bone formation Slower Maintenance of bone mass Bone formation Endochondral Periosteal Bone resorption Endosteal Bone reshaping and growth Coupled Uncoupled Immune Factors T cells (INF-γ, RANKL) TNF , IL-6 Nutrition Calcium, vitamin D Caloric/Protein intake Vitamin K Micronutrients Delayed sexual maturation  IGF-I Inactivity  Lean tissue mass Medications Sylvester, Inflamm Bowel Dis 2005; 11:1020-3

14. Bone Health in Children with IBD Bone mineral density (BMD) is often reduced in children with IBD and may reduce peak bone mass in adulthood. Low trauma and vertebral compression fractures can occur, particularly in adulthood. Low BMD does not reliably predict future fractures in children or adults with IBD – most who fracture have normal BMD. DXA measurement of BMD does not reliably estimate bone strength or predict future fractures. DXA measurement of BMD has modest impact upon clinical management beyond nutritional and medical therapy already offered to all patients.