1. Managing Osteoporosis in the New Millennium Elena Barengolts, MD Associate Professor of Medicine University of Illinois at Chicago College of Medicine

2. Osteoporosis A disease of women, occasionally men, and rarely men who dress like women

3. Case #1 Mrs. White is an 82 year old female, nursing home resident who has just returned to the nursing home following repair of a hip fracture she sustained during a fall. She has mild dementia (follows instructions) and a history of breast cancer.

4. 1.3 million fractures per year Osteoporosis is 3 times more common than breast cancer Cost - $10 - 12 billion in 1990 - $50 billion in 2040 Osteoporosis Epidemiology

5. Case #2 Miss Scarlett is a 92 year old woman who has recently suffered a painful vertebral fracture. She is in a wheelchair due to a stroke she suffered 4 years ago. Her creatinine is 2.4. She is frail with significant kyphosis.

6. Osteoporosis: More Common than Heart Attack in Women Annual Incidence of Common Disease Osteoporotic Fracture > 1,000,000* Heart Attack 513,000** Stroke 228,000^ Breast Cancer 182,000^^ Uterine Cancer 32,800^^ Ovarian Cancer 26,600^^ Cervical Cancer 15,800^^ *1993 estimated all ages^1991 estimated, women 30+ ** 1991 estimated, women 29+^^1995 new cases, all women

7. Case #3 Colonel Mustard who has suffered with symptomatic GERD for the last 10 years, falls and breaks a hip. He is 65 years old and has no apparent risk for osteoporosis.

8. Hip Fracture Outcomes 24% mortality within first year 1 50% of hip fracture sufferers unable to walk without assistance 2 ~ 33% totally dependent 3 7.8% need long-term nursing home care for an average of 7.6 years 4 1 Ray, NF et al. J Bone Miner Res 1997; 12:24-35 2 Riggs, BL, Melton LJ III. Bone 1995; 17 (Suppl): 505S-511S 3 Kannus, P et al. Bone 1996;18 (Suppl): 57S-63S 4 Chrischilles EA et al. Arch Intern Med 1991; 151: 2026-32

9. Case #4 Professor Plum who is an expert on osteoporosis, is worried about his 50 yo daughter. Her mother, the professor’s wife, recently had a hip fracture due to severe osteoporosis. Ms. Plum is of small build, smokes cigarettes 1 ppd x 25 y, drinks lots of coffee and is a self-admitted couch potato. She refuses HRT but agrees to a DEXA. Her T-score is -1.7 at the L spine and -1.8 at the hip.

10. Modifiable Risk Factors Behavioral Inactivity Alcohol abuse Cigarette smoking Nutritional Low calcium intake Low vitamin D intake Caffeine excess Drugs Low BMD

11. Case #5 Mr. Green is a 70 year old man with a recent history of prednisone use to manage temporal arteritis. He recently sustained a fracture of the left wrist after falling down his stairs. A DEXA scan reveals a T- score of -2.6 at the hip and -2.0 at the lumbar spine.

12. Drugs Glucocorticoids Thyroid hormone excess Anticonvulsants Heparin, warfarin Cyclosporin A Methotrexate GnRH analogs

14. Case #7 Sorry, no chance to help Mr. Body. He was found dead, in the hall, after tripping over the candlestick, falling down the stairs and breaking both hips! If only his doctor had identified his advanced osteoporosis.

15. Osteoporosis: Evaluation Bone mass measurement devices Central Peripheral Bone turnover

16. Osteoporosis: Diagnosis and Evaluation Central DXA (Dual Energy X-ray Absorptiometry) remains the state-of- the-art diagnostic standard Bone density is the most important predictor of fracture risk

18. WHO, Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis, 1998. T - Score World Health Organization (WHO) Osteoporosis Guidelines

20. Osteoporosis prevention and screening Increased dietary calcium & Vit. D Exercise - weight bearing (walking, dancing, some exercise classes) Recommend a BMD test

25. Calcium absorption Adult average 30% (20-70%) Most efficient-Duodenum, proximal jejunum Largest amount- distal jejunum, ileum Mechanism: Cellular=active: in vesicles & and bound to calbindin Paracellular=passive: diffusion Vitamin D: increased synthesis of calbindin Other factors Estrogen: via increased vit D synthesis Glucocort: via reduced paracellular diffusion Thyrotoxicosis & acidosis: via decreased vit D syn Alcohol: direct toxic effect on enterocytes Endocrinology Ed. L. DeGroot Saunders Co 2001, pp.1030-1033

26. Calcium bioavailability RDA for Ca 1000 mg/day Increased: growth spurt, pregnancy intestinal pH 4-6 – after a meal bile salts lactose: milk Decreased: Aging dietary high fiber: impair bile reabsorption Phytates/ cellulose: wheat bran cereal oxalate: spinach, rhubarb, tea Neutral or negligible effect: Protein, fat, magnesium, phosporus, caffeine Heaney RP et al, Consensus Opinion, Menopause 2001;8:84-95 Endocrinology Ed. L. DeGroot Saunders Co 2001, pp.1030-1033

27. Normal response to varying Ca intake Calcium mg/day Dietary intake Ca 2208502100 Absorbed Ca*150340490 Efficiency,%68423 Renal Ca excretion 150210260 Skeletal Ca uptake**420420420 Skeletal Ca release**530420350 Total Ca balance-110 0 +70 * diet-fecal calcium correcrted for endgns fecal Ca **values calculated with compartmental model Endocrinology Ed. L. DeGroot Saunders Co 2001, pp.1030-1033

28. Calcium intake- the best source of Ca is food Total calcium intake – most important With higher intake % absrbed dcrs but total amount absorbed increased Absorptive efficiency – individualized Is not completely understood Relates to nutrition, hormonal status, physical activity, drugs, alcohol

29. Calcium absorption From milk 30% From vegetables and grains same as milk or slightly better Less than milk: high phytic acid: wheat bran cereal, soy bean High oxalate: spinach (5% vs 30% milk) RP Heaney J Int Med 1992:231:169-180 RP Heaney, CM Weaver Am J Clin Nutr 1991;53:745-47;

30. Dietary intake estimation ProductCalcium (mg) Milk, whole/skim (8 oz.) 300 Yogurt - lowfat (8 oz.) 400 Cheese (1 oz.) 200 Ice cream, ½ cup 100 OJ - Ca fortified, (8 oz.) 300 Sardines w. bones (3 oz) 370 Salmon w. bones (3 oz) 200 Total = dairy Ca + 250 for all nondairy Practical Approach to Dietary Ca Heaney RP et al, Consensus Opinion, Menopause 2001;8:84-95

32. Dietary Changes for Vegetarians FOOD CA, mg Baked beans, 1/2 c. cooked154 Almonds, 1/4 cup 100 Sesame seeds, Tbsp 33 Broccoli, fresh, cooked, 1 c150 Bok choy, 1 c cooked/raw150/200 Collards, fresh, cooked, 1 c350 Turnip greens, 1 c200 Figs, dried, 10 figs270 Soybean curd (tofu), 4 oz150

33. Practical Approach to Dietary Ca Fortified foods CA, mg Soy milk, 1c100-300 Milk, 1c500 Cereal, w/o milk, 1c100-1000 Fruit juice, 1c300 Breakfast bars, 1 bar200-500 Heaney RP et al, Consensus Opinion, Menopause 2001;8:84-95

34. Practical Approach to Ca supplement Which is the best? When to take? With or between meal, bed time Once a day or divided doses?

35. Calcium absorption Coingestion with food - 20-25% improved absorbtion of both food and supplented Ca compared to empty stomach Improved absorbtion: Chewable, effervescent Divided doses but worse compliance Bed time - prevents PTH-mediated bone resorption during the fasting at night RP Heaney et al. Am J Clin Nutr 1989;49;372-6 RP Heaney J Int Med 1992;231:169-80

36. Ca supplement - absorption PreparationFractional absorption Hydroxyapatite0.203 ± 0.110 Tricalcium phosphate0.252 ± 0.13 Carbonate0.296 ± 0.054 Citrate0.296 ± 0.060 Bone meal/oyster shell0.333 ± 0.113 Bisglycinocalcium*0.440 ± 0.104 *Chelated to amino acids Carr CJ, Shangraw RF Am pharm 1987:NS27:49-57

37. Ca absorption from food FoodFractional absorption Milk0.339 ± 0.095 Spinach0.012 ± 0.007 Low phytate soybeans0.306 ± 0.054 Kale0.405 ± 0.101 Mean value ± SD measured under standard meal conditions RP Heaney J Int Med 1992;231:169-80

39. Risk Factors for vitamin D deficiency Lack of sunlight exposure Dietary lack Malabsorption Liver disease Renal disease Anticonvulsants

40. Vitamin D Considerations Casual exposure to sunlight provides most of our Vitamin D requirements At latitude 42º N (Chicago), ultraviolet exposure is inadequate for producing sufficient Vit D in the skin between November and February

41. Vitamin D fortified milk (8 oz = 50 IU) Egg yolk Liver of salt water fish = cod liver Fortified cereal (“Total” 1 cup 40 IU) 15 min. of daily sun exposure provides about 400 IU of Vit D Lifestyle Approach to Vit D

42. Practical Approach to Vit D Most multivitamins (200 - 400 IU) Cholecalciferol (D3) 400 IU in combination with Calcium (OTC) Ergocalciferol (D2) 50,000 IU or 8,000 IU/ml drops (Calciferol) Calcifediol (25 OH D3) 20, 50 mcg (Calderol) Calcitriol 1,25 (OH) 2 D 0.25 - 0.5 mcg (Rocaltrol)

43. Chinese Vegetable Stir-Fry Thickener:1/4 cup water,2 Tbsp light soy sauce, 1/8 tsp pepper, 1 tsp olive oil. Tofu Mixture:1 packet firm tofu, cut into 1/2 inch cubes and drained, 3/4 cup onion, cubed, 2 large cloves garlic, minced. Veggie: Chopped:1/2 bunch broccoli, 1 small zucchini, 1 cup green/red bell pepper, 1 cup collard, kale or bok choy, 2 large tomatoes, 1/2 cup vegetable broth. Method: In wok add oil & Tofu Mixture, stir-fry for 3-4 min. Onion and tofu should begin to brown. Add broth &Veggie and simmer for 10 min. Add tomatoes, cover and cook for 5 min. Add thickener and cook, stirring for 3 min. Serve over rice or noodles. Yield: 8 servings, per serving: cal 126 Kcal, carb 12 gm, protein: 10 gm, fat: 4 gm, calcium 200 mg

44. 2 cups 1% milk 2 cups cereal “Total” Mix in a bowl, stir for 30 sec Yield: 2 serving, per serving: calories 150, fat 8 g, carb 12 g, protein 8 g, calcium 800 mg