Osteoporosis

Internal Medicine Lecture Series Danielle Hansen DO, MS September 26, 2007

Definition

 Skeletal Disorder Characterized by Compromised Bone Strength Predisposing to an Increased Risk of Fracture.

Bone Strength = Bone Density + Bone Quality NIH Consensus Conference, 2000

Epidemiology

   8 Million Women and 2 Million Men have Osteoporosis 1 34 Million Americans have Low Bone Mass 1 50% of Women and 25% of Men >50 yo will Suffer an Osteoporosis-related Fracture within their Lifetime 2 Projected Prevalence in Those >50 Women with Osteoporosis 2002 7.8

2020 10.5

Women with Low Bone Mass Men with Osteoporosis Men with Low Bone Mass 21.8

2.3

11.8

30.4

3.3

17.1

Numbers in Millions 1.

2.

National Osteoporosis Foundation. America’s Bone Health: The state of Osteoporosis and Low Bone mass in our Nation. 2002 Chrischilles EA, et al. Arch Intern. Med. 1991; 151, 2026-32

Osteoporotic Fracture Incidence

2 Million Fractures Annually in Pts >50 yo 2° to Osteoporosis  300,000 Hip Fx    550,000 Vertebral Fx 400,000 Wrist Fx 810,000 Other Annual Incidence of Common Diseases

1600000 1456000 1400000 1200000 1000000 800000 600000 400000 200000 0 Osteoporotic FX 345000 373000 269730

MI

CVA

Breast CA Burge, et al. JBMR. 2007. 465-75

Cost of Osteoporosis

  Osteoporotic Fractures Account for:  $17 Billion in Direct medical Costs 1    >400,000 Hospital Admissions 3 2.5 Million Physician Visits 3 >180,000 Nursing Home Admissions 3 Projected Annual Direct Costs:  $25.3 Billion by 2025 1  $50 Billion by 2040 2 1.

2.

3.

Burge, et al. JBMR. 2007. 465-75.

Ray, NF, et al. J Bone Min Res. 1997; 12: 24-35.

National Osteoporosis Foundation, Osteoporosis Int. 1998; 8: S1-S88.

Risk Factors for Osteoporotic Fx

      Genetics   Low Peak Bone Mass 1 Small, Thin Frame 2 Race  Whites and Asians > Latinas > AA 3 Women > Men Adult Fracture Relative with Adult Fracture Smoking          Advancing Age Imparied Vision Dementia Poor Health Estrogen Deficiency < 45 yo Frequent Falls Lifelong Low Calcium Intake Sedentary Lifestyle EToH Consumption 1. Riggs, BL et al. N Eng J Med. 1986; 314(26): 1676-86.

2. Gunnes, M, et al. Bone. 1996; 4: 407-13.

3. NOF, 2007.

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Osteoporosis 2° to Disease

RA Other Autoimmune Hyperparathyroidism Hypogonadism Hyperprolactinemia Acromegaly Hypercortisolism Hyperthyroidism IBD Celiac Disease Malabsorption Syndromes Biliary Sclerosis Sclerosing Choangitis Alcoholic Cirrhosis Autoimmune Hepatitis IDDM Organ Transplantation Multiple Myeloma Osteogenesis Imperfecta Pernicious Anemia Sarcoidosis                     Anorexia/Bulimia Calcium Deficiency Excessive Vitamin A TPN Stroke MS Parkinson’s Disease Spinal Cord Injury Immobilization Renal Disease Addison’s Disease Amyloidosis Ankylosing Spondylitis COPD Cushing Syndrome Endometriosis Hemophilia Hemochromatosis Lymphoma Leukemia

Osteoporosis 2° to Medications

     Glucocorticoids Aromatase Inhibitors Gonadotropin releasing Hormone Agonists Immunosuppressants Cytotoxics       ? PPIs ?

? SSRIs ?

Phenobarbital Phenytoin Lithium Heparin Depo-Provera TPN

Bone Loss with Aging

Lose 20% of Bone in First 5-7 years after Menopause

Fracture Risk with Aging

  Hip Fractures Increase Sharply >70 Vertebral Fractures Increase Linearly >40

Fracture Risk with Bone Density

Exponential Increase in Risk of Fracture with Worsening BMD

Vertebral Fractures

  Prior Vertebral Fracture:   Increases Vertebral Fracture Risk 5-fold 1 Increases Hip Fracture Risk 2-fold 2 Silent Fractures Common 1.

2.

lindsay, R et al. JAMA. 2001 Jan 17;285(3):320-3.

Black, DM, et al. J Cone Miner Res. 1999 May;14(5):821-8.

Hip Fracture

     10-24% Death in Year Following Fx 1 Up to 30% Require ECF 15% Walk Unaided 6 Months after Fx <20% Regain Premorbid Level of Functioning 2 <5% Fracture Admissions are Evaluated for Osteoporosis 1.

2.

Forsen, L et al. Osteoporosis Int. 1999;10:73-78.

Van Balen, R et al. Disabil Rehab. 2003 May 20;25(10):507-19.

Diagnosis: DXA

Central Machine Hip, Sine, Forearm, Total Body Diagnostic Monitor Response to Tx q 1 2 years Peripheral Machine Wrist, Heel, Finger Identify Pts at Risk Cannot Monitor Tx Response

Diagnosis: WHO Criteria

   Defines Osteoporosis in Relation to Expected Distribution of BMD for Young, Normal Adults of Same Sex T-Score Expressed as Standard Deviations Above (+) or Below (-) the Young Reference Mean Value  One SD = 10-15% of BMD Criteria Apply to Hip, Spine, Wrist

Indications for DXA

   Women >64 Younger Postmenopausal Women with 1 Other Risk Factor Postmenopausal Women with Fracture

DXA Medicare Coverage

 Every 2 Years for:      Estrogen Deficient Women at Risk Vertebral Abnormalities Long-Term Glucocorticoid Therapy Primary Hyperparathyroidism Assess Response to Treatment

Universal Prevention/Treatment Strategies

      Risk Reduction Adequate Daily Intake of Calcium and Vitamin D Weight-Bearing and Muscle Strengthening Exercises Fall Prevention Tobacco Cessation EToH Cessation

Calcium

Recommendations Age 1-8 9-18 19-49 >50 Mg/day 500-800 1300 1000 1200 + Meals Supplement 700mg 500mg 1200mg

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Vitamin D

Essential for Absorption of Calcium from GI Tract >50 need 800-1000 IU/day <50 need 400-800 IU/day Vitamin D Synthesized in Skin Upon Exposure to Sunlight  Blocked by Sunscreen (SPF 8 Blocks 95%) Fortified Foods 1,25-dihydroxyvitamin D Form 3 is Biologically Active Monitor Serum 25-hydroxyvitamin D >80nmol/L) 3 (Goal

Indications for Pharmacologic Therapy

Options for Pharmacologic Therapy

  Antiresorptives (Bone Retaining)  Bisphosphonates   Inhibit Osteoclasts Administration Guidelines    Calcitonin Estrogen/Hormone Therapy Raloxifene Anabolics  Synthetic PTH

Bisphosphonates

   Dosage:   35mg q wk for Prevention 70mg q wk for Treatment FIT-I 51% Reduction in Hip Fractures at 3yrs Also Effective with Glucocorticcoids   Dosage:  35mg q wk Trials:    61-65% Reduction in Vertebral Fractures 55% Reduction in Hip Fractures 70% Reduction in vertebral Fractures in Glucocorticcoid Pts

Calcitonin

   At Least 5 Years Postmenopausal and Unable to Tolerate Other Therapy Reduced Risk of Vertebral Fractures but Not Other Fractures Nasal Spray or Injectable

Evista

    Selective Estrogen Receptor Modulator that Acts as an Estrogen Agonist on Bone but as an Estrogen Antagonist on Breast and Uterus Reduced Risk of Vertebral Fractures, but Not Other Fractures Significant Fracture Reduction in Glucocorticcoids but no Indication Reduced Risk of Breast Cancer by 66-72%

Hormone Therapy

  WHI Findings:    34% Reduction in Hip Fractures 23% Reduction in Other Osteoporotic Fractures 24% Reduction in all Fractures Controversial

Treatment Summary

Challenge

     Identify and Treat High Risk Patients Recognize Risk Factors that Call For Screening Assess Diet and Lifestyle Treat Appropriately Rule out Other Diseases