1. Osteoporosis in IBD

2. General Risk Factors for Osteoporosis Advancing age Advancing age Female gender Female gender Family history Family history Alcohol use Alcohol use White/Asian race White/Asian race Smoking Smoking Physical inactivity Physical inactivity Low calcium intake Low calcium intake Small and thin body habitus Small and thin body habitus Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94:878-883. Christchilles EA, et al. Arch Intern Med. 1991;151:2026-2032.

3. Risk of Osteoporosis in IBD Low bone mass in 31% to 59% of IBD patients 1-3 Low bone mass in 31% to 59% of IBD patients 1-3 IBD-related risk factors 4 IBD-related risk factors 4 –Onset of IBD before reaching age of peak bone mass –Inflammatory cytokines –Calcium malabsorption –Vitamin D deficiency (CD patients) –Drugs (corticosteroids, methotrexate, cyclosporine) 1 Compston JE. Aliment Pharmacol Ther. 1995;9:237-250. 2 Roux C, et al. Osteoporos Int. 1995;5:185-190. 3 Andreassen H, et al. Scand J Gastroenterol. 1997;32:1247-1255. 4 Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94:878-883.

4. Prevention and Treatment of Osteoporosis in IBD Prevention Prevention –Baseline and follow-up measurements of bone density (DEXA) –Lifestyle and nutritional measures (eg, weight-bearing exercise, smoking cessation, calcium supplementation) –Possible HRT for high-risk postmenopausal women Treatment Treatment –Calcitonin– PTH –Bisphosphonates– IV therapies Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94:878-883.

5. Corticosteroid-Induced Bone Loss Bone loss occurs early (weeks to months after initiation of therapy) Bone loss occurs early (weeks to months after initiation of therapy) Cumulative dose, dosage, and duration of corticosteroids may play a role Cumulative dose, dosage, and duration of corticosteroids may play a role Calcium and small doses of vitamin D may confer limited prophylactic benefit Calcium and small doses of vitamin D may confer limited prophylactic benefit Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94:878-883. Van Staa TP, et al. J Bone Mineral Res. 2000;15:993-1000.

6. Corticosteroid-Induced Loss of Bone Mass Enhanced bone resorption Enhanced bone resorption –Reduced intestinal calcium absorption and calcitonin synthesis –Increased renal calcium excretion, osteoclastic activity, and parathyroid hormone secretion –Enhanced binding of macrophages to bone Reduced bone formation Reduced bone formation –Reduced synthesis of osteoblasts and proliferation of osteoblasts –Impaired gonadal hormone production –Prednisone associated with increased rate of bone loss –Conflicting data regarding budesonide

7. Reducing the Risk of Osteoporosis History and physical lab (25-hydroxy vitamin D, albumin, calcium, PTH) Bone density (DEXA) Minimize corticosteroids Normal T Score Low BMD: T Score <–1 SD Osteoporosis: T Score <–2.5 SD Monitor regularly Hormone (if appropriate) Raloxifene (if appropriate) Calcium Vitamin D General guidelines Repeat DEXA Hormone (if appropriate) Raloxifene (if appropriate) Calcium Vitamin D Bisphosphonates General guidelines Repeat DEXA

8. -4 Months Placebo Ris 5.0 mg *P<.05 vs baseline P<.05 vs control P<.05 vs control Prevention Study Treatment Study 12 month diff. = 3.8% 12 month diff. = 2.7% % Change from Baseline Lumbar Spine BMD -3 -2 0 1 2 036912 * * * Bisphosphonates in the Prevention and Treatment of Osteoporosis Cohen S, Levy RM, Keller M, Boling E, et al. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 1999;42:2309-2318. Copyright© American College of Rheumatology. Reproduced with permission of John Wiley & Sons, Inc. Reproduced from J Bone Miner Res. 2000:15;1006-1013 with permission of the American Society for Bone and Mineral Research. 0 Months 1 2 3 4 0612 * * * * *

9. Infliximab in Patients With CD and Osteoporosis Prospective, 4-week trial with patients taking corticosteroids Prospective, 4-week trial with patients taking corticosteroids Significant decrease in CDAI with infliximab (P=.0001) Significant decrease in CDAI with infliximab (P=.0001) Increase in surrogate markers for bone turnover Increase in surrogate markers for bone turnover Conclusion: increased bone synthesis with no increase in bone resorption Conclusion: increased bone synthesis with no increase in bone resorption CDAI = Crohns disease activity index. Abreu MT, et al. Am J Gastroenterol. 2002;97:S269. Abstract 819.

10. Summary: Osteoporosis and IBD Bone density is unusually low in patients with active IBD who are taking steroids Bone density is unusually low in patients with active IBD who are taking steroids IBD causes other risk factors, eg, poor calcium absorption and disease-related inflammatory processes, that increase risk of bone loss IBD causes other risk factors, eg, poor calcium absorption and disease-related inflammatory processes, that increase risk of bone loss Monitoring BMD is important Monitoring BMD is important Selection of treatment should be considered Selection of treatment should be considered