Managing Osteoporosis in the New Millennium

Elena Barengolts, MD

Associate Professor of Medicine

University of Illinois at Chicago College of Medicine

Osteoporosis

A disease of women, occasionally men, and rarely men

who dress like women

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.

• 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

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.

Osteoporosis: More Commonthan 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

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.

Hip Fracture Outcomes

• 24% mortality within first year1

• 50% of hip fracture sufferers unable to walk without assistance2

• ~ 33% totally dependent3

• 7.8% need long-term nursing home care for an average of 7.6 years4

1 Ray, NF et al. J Bone Miner Res 1997; 12:24-352 Riggs, BL, Melton LJ III. Bone 1995; 17 (Suppl): 505S-511S3 Kannus, P et al. Bone 1996;18 (Suppl): 57S-63S4 Chrischilles EA et al. Arch Intern Med 1991; 151: 2026-32

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.

Modifiable Risk Factors

• BehavioralInactivityAlcohol abuseCigarette smoking

• NutritionalLow calcium intakeLow vitamin D intakeCaffeine excess

• Drugs• Low BMD

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.

Drugs

• Glucocorticoids

• Thyroid hormone

excess

• Anticonvulsants

• Heparin, warfarin

• Cyclosporin A

• Methotrexate

• GnRH analogs

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.

Osteoporosis: Evaluation

• Bone mass measurement devices

• Central

• Peripheral

• Bone turnover

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 offracture risk

WHO, Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis, 1998.

T - Score

World Health Organization (WHO) Osteoporosis Guidelines

Osteoporosis prevention and screening

• Increased dietary calcium & Vit. D

• Exercise - weight bearing (walking, dancing, some exercise classes)

• Recommend a BMD test

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

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;8:84-95Endocrinology Ed. L. DeGroot Saunders Co 2001, pp.1030-1033

Normal response to varying Ca intake

• Calcium mg/day • Dietary intake Ca 220 850 2100• Absorbed Ca* 150 340 490• Efficiency,% 68 4 23• Renal Ca excretion 150 210 260 • Skeletal Ca uptake** 420 420 420• Skeletal Ca release** 530 420 350• 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

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

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;

Dietary intake estimation

Product Calcium (mg)Milk, whole/skim (8 oz.) 300Yogurt - lowfat (8 oz.) 400Cheese (1 oz.) 200Ice cream, ½ cup 100OJ - Ca fortified, (8 oz.) 300 Sardines w. bones (3 oz) 370Salmon w. bones (3 oz) 200Total = dairy Ca + 250 for all nondairy

Practical Approach to Dietary Ca

Heaney RP et al, Consensus Opinion, Menopause 2001;8:84-95

Dietary Changes for Vegetarians

FOOD CA, mg Baked beans, 1/2 c. cooked 154 Almonds, 1/4 cup 100 Sesame seeds, Tbsp 33 Broccoli, fresh, cooked, 1 c 150 Bok choy, 1 c cooked/raw 150/200 Collards, fresh, cooked, 1 c 350 Turnip greens, 1 c 200 Figs, dried, 10 figs 270 Soybean curd (tofu), 4 oz 150

Practical Approach to Dietary Ca

Fortified foods CA, mgSoy milk, 1c 100-300Milk, 1c 500Cereal, w/o milk, 1c 100-1000Fruit juice, 1c 300Breakfast bars, 1 bar 200-500

Heaney RP et al, Consensus Opinion, Menopause 2001;8:84-95

Practical Approach to Ca supplement

• Which is the best?

• When to take?

• With or between meal, bed time

• Once a day or divided doses?

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

Ca supplement - absorption

• Preparation Fractional absorption• Hydroxyapatite 0.203 ± 0.110• Tricalcium phosphate 0.252 ± 0.13• Carbonate 0.296 ± 0.054• Citrate 0.296 ± 0.060• Bone meal/oyster shell 0.333 ± 0.113• Bisglycinocalcium* 0.440 ± 0.104 *Chelated to amino acids

Carr CJ, Shangraw RF Am pharm 1987:NS27:49-57

Ca absorption from food

• Food Fractional absorption• Milk 0.339 ± 0.095• Spinach 0.012 ± 0.007• Low phytate soybeans 0.306 ± 0.054• Kale 0.405 ± 0.101• Mean value ± SD measured under

standard meal conditions

RP Heaney J Int Med 1992;231:169-80

Risk Factors for vitamin D deficiency

• Lack of sunlight exposure• Dietary lack• Malabsorption• Liver disease• Renal disease• Anticonvulsants

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

• 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

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)

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

• 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