OsteoporosisOsteoporosisInternal Medicine Lecture Internal Medicine Lecture

SeriesSeries

Danielle Hansen DO, MSDanielle Hansen DO, MS

September 26, 2007September 26, 2007

DefinitionDefinition Skeletal Disorder Characterized by Skeletal Disorder Characterized by

Compromised Bone Strength Compromised Bone Strength Predisposing to an Increased Risk of Predisposing to an Increased Risk of Fracture.Fracture.

Bone Strength Bone Strength = Bone = Bone

Density + Density + Bone QualityBone Quality

NIH Consensus Conference, 2000

EpidemiologyEpidemiology

8 Million Women and 2 8 Million Women and 2 Million Men have Million Men have OsteoporosisOsteoporosis11

34 Million Americans 34 Million Americans have Low Bone Masshave Low Bone Mass11

50% of Women and 50% of Women and 25% of Men >50 yo 25% of Men >50 yo will Suffer an will Suffer an Osteoporosis-related Osteoporosis-related Fracture within their Fracture within their LifetimeLifetime22

1. National Osteoporosis Foundation. America’s Bone Health: The state of Osteoporosis and Low Bone mass in our Nation. 2002

2. Chrischilles EA, et al. Arch Intern. Med. 1991; 151, 2026-32

20022002 20202020Women Women

with with OsteoporosOsteoporos

isis

7.87.8 10.510.5

Women Women with Low with Low

Bone MassBone Mass

21.821.8 30.430.4

Men with Men with OsteoporosOsteoporos

isis

2.32.3 3.33.3

Men with Men with Low Bone Low Bone

MassMass

11.811.8 17.117.1Numbers in Millions

Projected Prevalence in Those >50

Osteoporotic Fracture Osteoporotic Fracture IncidenceIncidence

2 Million Fractures2 Million Fractures

Annually in Pts >50 Annually in Pts >50 yoyo

22° to Osteoporosis° to Osteoporosis 300,000 Hip Fx300,000 Hip Fx 550,000 Vertebral 550,000 Vertebral

FxFx 400,000 Wrist Fx400,000 Wrist Fx 810,000 Other810,000 Other

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

1456000

345000 373000269730

0

200000

400000

600000

800000

1000000

1200000

1400000

1600000

OsteoporoticFX

CVAMI Breast CA

Annual Incidence of Common Diseases

Cost of OsteoporosisCost of Osteoporosis

Osteoporotic Fractures Account for:Osteoporotic Fractures Account for: $17 Billion in Direct medical Costs$17 Billion in Direct medical Costs11

>400,000 Hospital Admissions>400,000 Hospital Admissions33

2.5 Million Physician Visits2.5 Million Physician Visits33

>180,000 Nursing Home Admissions>180,000 Nursing Home Admissions33

Projected Annual Direct Costs:Projected Annual Direct Costs: $25.3 Billion by 2025$25.3 Billion by 202511

$50 Billion by 2040$50 Billion by 204022

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

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

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

Risk Factors for Risk Factors for Osteoporotic FxOsteoporotic Fx

GeneticsGenetics Low Peak Bone MassLow Peak Bone Mass11

Small, Thin FrameSmall, Thin Frame22

RaceRace Whites and Asians > Whites and Asians >

Latinas > AALatinas > AA33

Women > MenWomen > Men Adult FractureAdult Fracture Relative with Adult Relative with Adult

FractureFracture SmokingSmoking

Advancing AgeAdvancing Age Imparied VisionImparied Vision DementiaDementia Poor HealthPoor Health Estrogen Deficiency < 45 Estrogen Deficiency < 45

yoyo Frequent FallsFrequent Falls Lifelong Low Calcium IntakeLifelong Low Calcium Intake Sedentary LifestyleSedentary Lifestyle EToH ConsumptionEToH 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.

Osteoporosis 2Osteoporosis 2° to Disease° to Disease RARA Other AutoimmuneOther Autoimmune HyperparathyroidismHyperparathyroidism HypogonadismHypogonadism HyperprolactinemiaHyperprolactinemia AcromegalyAcromegaly HypercortisolismHypercortisolism HyperthyroidismHyperthyroidism IBDIBD Celiac DiseaseCeliac Disease Malabsorption SyndromesMalabsorption Syndromes Biliary SclerosisBiliary Sclerosis Sclerosing ChoangitisSclerosing Choangitis Alcoholic CirrhosisAlcoholic Cirrhosis Autoimmune HepatitisAutoimmune Hepatitis IDDMIDDM Organ TransplantationOrgan Transplantation Multiple MyelomaMultiple Myeloma Osteogenesis ImperfectaOsteogenesis Imperfecta Pernicious AnemiaPernicious Anemia SarcoidosisSarcoidosis

Anorexia/BulimiaAnorexia/Bulimia Calcium DeficiencyCalcium Deficiency Excessive Vitamin AExcessive Vitamin A TPNTPN StrokeStroke MSMS Parkinson’s DiseaseParkinson’s Disease Spinal Cord InjurySpinal Cord Injury ImmobilizationImmobilization Renal DiseaseRenal Disease Addison’s DiseaseAddison’s Disease AmyloidosisAmyloidosis Ankylosing SpondylitisAnkylosing Spondylitis COPDCOPD Cushing SyndromeCushing Syndrome EndometriosisEndometriosis HemophiliaHemophilia HemochromatosisHemochromatosis LymphomaLymphoma LeukemiaLeukemia

Osteoporosis 2Osteoporosis 2° to ° to MedicationsMedications

GlucocorticoidsGlucocorticoids Aromatase Aromatase

InhibitorsInhibitors Gonadotropin-Gonadotropin-

releasing Hormone releasing Hormone AgonistsAgonists

ImmunosuppressanImmunosuppressantsts

CytotoxicsCytotoxics

PhenobarbitalPhenobarbital PhenytoinPhenytoin LithiumLithium HeparinHeparin Depo-ProveraDepo-Provera TPNTPN

? PPIs ?? PPIs ?? SSRIs ?? SSRIs ?

Bone Loss with AgingBone Loss with Aging

Lose 20% Lose 20% of Bone in of Bone in First 5-7 First 5-7

years after years after MenopauseMenopause

Fracture Risk with AgingFracture Risk with Aging

Hip Hip Fractures Fractures Increase Increase Sharply >70Sharply >70

Vertebral Vertebral Fractures Fractures Increase Increase Linearly Linearly >40>40

Fracture Risk with Bone Fracture Risk with Bone DensityDensity

Exponential Exponential Increase in Increase in

Risk of Risk of Fracture with Fracture with

Worsening Worsening BMDBMD

Vertebral FracturesVertebral Fractures Prior Vertebral Fracture:Prior Vertebral Fracture:

Increases Vertebral Fracture Risk 5-foldIncreases Vertebral Fracture Risk 5-fold11

Increases Hip Fracture Risk 2-foldIncreases Hip Fracture Risk 2-fold22

Silent Fractures CommonSilent Fractures Common

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

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

Hip FractureHip Fracture 10-24% Death in Year Following Fx10-24% Death in Year Following Fx11

Up to 30% Require ECFUp to 30% Require ECF 15% Walk Unaided 6 Months after Fx15% Walk Unaided 6 Months after Fx <20% Regain Premorbid Level of <20% Regain Premorbid Level of

FunctioningFunctioning22

<5% Fracture Admissions <5% Fracture Admissions

are Evaluated for Osteoporosisare Evaluated for Osteoporosis

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

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

Diagnosis: DXADiagnosis: DXACentral MachineCentral Machine Peripheral MachinePeripheral Machine

Hip, Sine, Forearm, Total Hip, Sine, Forearm, Total BodyBody

Wrist, Heel, FingerWrist, Heel, Finger

DiagnosticDiagnostic Identify Pts at RiskIdentify Pts at Risk

Monitor Response to Tx q Monitor Response to Tx q 1-2 years1-2 years

Cannot Monitor Tx Cannot Monitor Tx ResponseResponse

Diagnosis: WHO CriteriaDiagnosis: WHO Criteria Defines Osteoporosis in Defines Osteoporosis in

Relation to Expected Relation to Expected Distribution of BMD for Distribution of BMD for Young, Normal Adults of Young, Normal Adults of Same SexSame Sex

T-Score Expressed as T-Score Expressed as Standard Deviations Standard Deviations Above (+) or Below (-) Above (+) or Below (-) the Young Reference the Young Reference Mean ValueMean Value One SD = 10-15% of BMDOne SD = 10-15% of BMD

Criteria Apply to Hip, Criteria Apply to Hip, Spine, WristSpine, Wrist

Indications for DXAIndications for DXA

Women >64Women >64 Younger Postmenopausal Women Younger Postmenopausal Women

with 1 Other Risk Factor with 1 Other Risk Factor Postmenopausal Women with Postmenopausal Women with

FractureFracture

DXA Medicare CoverageDXA Medicare Coverage

Every 2 Years for:Every 2 Years for: Estrogen Deficient Women at RiskEstrogen Deficient Women at Risk Vertebral AbnormalitiesVertebral Abnormalities Long-Term Glucocorticoid TherapyLong-Term Glucocorticoid Therapy Primary HyperparathyroidismPrimary Hyperparathyroidism Assess Response to TreatmentAssess Response to Treatment

Universal Prevention/Treatment Universal Prevention/Treatment StrategiesStrategies

Risk ReductionRisk Reduction Adequate Daily Intake of Calcium and Adequate Daily Intake of Calcium and

Vitamin DVitamin D Weight-Bearing and Muscle Strengthening Weight-Bearing and Muscle Strengthening

ExercisesExercises Fall PreventionFall Prevention Tobacco CessationTobacco Cessation EToH CessationEToH Cessation

CalciumCalcium

AgeAge Mg/dayMg/day

1-81-8 500-800500-800

9-189-18 13001300

19-4919-49 10001000

>50>50 12001200

Recommendations

Meals 700mg

Supplement 500mg

1200mg

+

Vitamin DVitamin D Essential for Absorption of Calcium from GI Essential for Absorption of Calcium from GI

TractTract >50 need 800-1000 IU/day>50 need 800-1000 IU/day <50 need 400-800 IU/day<50 need 400-800 IU/day Vitamin D Synthesized in Skin Upon Vitamin D Synthesized in Skin Upon

Exposure to Sunlight Exposure to Sunlight Blocked by Sunscreen (SPF 8 Blocks 95%)Blocked by Sunscreen (SPF 8 Blocks 95%)

Fortified FoodsFortified Foods 1,25-dihydroxyvitamin D1,25-dihydroxyvitamin D3 3 is Biologically is Biologically

Active FormActive Form Monitor Serum 25-hydroxyvitamin DMonitor Serum 25-hydroxyvitamin D3 3 (Goal (Goal

>80nmol/L)>80nmol/L)

Indications for Pharmacologic Indications for Pharmacologic TherapyTherapy

Options for Pharmacologic Options for Pharmacologic TherapyTherapy

Antiresorptives (Bone Retaining)Antiresorptives (Bone Retaining) BisphosphonatesBisphosphonates

Inhibit OsteoclastsInhibit Osteoclasts Administration GuidelinesAdministration Guidelines

CalcitoninCalcitonin Estrogen/Hormone TherapyEstrogen/Hormone Therapy RaloxifeneRaloxifene

AnabolicsAnabolics Synthetic PTHSynthetic PTH

BisphosphonatesBisphosphonates

Dosage:Dosage: 35mg q wk for 35mg q wk for

PreventionPrevention 70mg q wk for 70mg q wk for

TreatmentTreatment FIT-I 51% Reduction FIT-I 51% Reduction

in Hip Fractures at in Hip Fractures at 3yrs3yrs

Also Effective with Also Effective with GlucocorticcoidsGlucocorticcoids

Dosage:Dosage: 35mg q wk35mg q wk

Trials:Trials: 61-65% Reduction in 61-65% Reduction in

Vertebral FracturesVertebral Fractures 55% Reduction in 55% Reduction in

Hip FracturesHip Fractures 70% Reduction in 70% Reduction in

vertebral Fractures vertebral Fractures in Glucocorticcoid in Glucocorticcoid PtsPts

CalcitoninCalcitonin

At Least 5 Years Postmenopausal and At Least 5 Years Postmenopausal and Unable to Tolerate Other TherapyUnable to Tolerate Other Therapy

Reduced Risk of Vertebral Fractures Reduced Risk of Vertebral Fractures but Not Other Fractures but Not Other Fractures

Nasal Spray or InjectableNasal Spray or Injectable

EvistaEvista

Selective Estrogen Receptor Modulator Selective Estrogen Receptor Modulator that Acts as an Estrogen Agonist on Bone that Acts as an Estrogen Agonist on Bone but as an Estrogen Antagonist on Breast but as an Estrogen Antagonist on Breast and Uterusand Uterus

Reduced Risk of Vertebral Fractures, but Reduced Risk of Vertebral Fractures, but Not Other FracturesNot Other Fractures

Significant Fracture Reduction in Significant Fracture Reduction in Glucocorticcoids but no IndicationGlucocorticcoids but no Indication

Reduced Risk of Breast Cancer by 66-72%Reduced Risk of Breast Cancer by 66-72%

Hormone TherapyHormone Therapy

WHI Findings:WHI Findings: 34% Reduction in Hip Fractures34% Reduction in Hip Fractures 23% Reduction in Other Osteoporotic 23% Reduction in Other Osteoporotic

FracturesFractures 24% Reduction in all Fractures24% Reduction in all Fractures

ControversialControversial

Treatment SummaryTreatment Summary

ChallengeChallenge Identify and Treat Identify and Treat

High Risk PatientsHigh Risk Patients Recognize Risk Recognize Risk

Factors that Call For Factors that Call For ScreeningScreening

Assess Diet and Assess Diet and LifestyleLifestyle

Treat AppropriatelyTreat Appropriately Rule out Other Rule out Other

DiseasesDiseases