Critical Challenges in OsteoporosisCritical Challenges in OsteoporosisPrevention and TreatmentPrevention and Treatment

                Completing the Journey From Trial- andCompleting the Journey From Trial- and

Expert-Based Information to Clinical ApplicationExpert-Based Information to Clinical Applicationin The Primary Care Settingin The Primary Care Setting

Screen & InterveneScreen & InterveneCritical Challenges in Osteoporosis Critical Challenges in Osteoporosis

and Women’s Healthand Women’s Health

Critical Challenges in OsteoporosisCritical Challenges in OsteoporosisPrevention and Treatment Prevention and Treatment

►Osteoporosis-An Undertreated ConditionOsteoporosis-An Undertreated Condition►Complications of Osteoporotic FracturesComplications of Osteoporotic Fractures► Indications for ScreeningIndications for Screening► Interpretation of BMD MeasurementsInterpretation of BMD Measurements►Aggregate Analysis of Risk Factors Aggregate Analysis of Risk Factors

What Have We Learned Thus Far—A SummaryWhat Have We Learned Thus Far—A Summary

► Treatment Indications and TriggersTreatment Indications and Triggers► Pharmacological Therapy for Fracture Pharmacological Therapy for Fracture

Prevention Prevention ► Relationship between BMD changes and Relationship between BMD changes and

Vertebral/Nonvertebral Fractures Vertebral/Nonvertebral Fractures ► Vertebral and Nonvertebral Fracture PreventionVertebral and Nonvertebral Fracture Prevention► We will now discuss Adherence/Compliance, We will now discuss Adherence/Compliance,

and Their Relationship to Outcomesand Their Relationship to Outcomes

What Have We Learned Thus Far—A SummaryWhat Have We Learned Thus Far—A Summary

Critical Challenges in OsteoporosisCritical Challenges in OsteoporosisPrevention and Treatment Prevention and Treatment

DefinitionsDefinitions

►   Initiation-Initiation- Getting the prescription filled. Getting the prescription filled. About 10% of prescriptions are never About 10% of prescriptions are never filled.    filled.    

► Adherence-Adherence- Taking the medicine. Taking the medicine. Often defined as taking more than  80% of Often defined as taking more than  80% of pills over a specified period of time.    pills over a specified period of time.    

► Compliance-Compliance- Taking the pills correctly. Taking the pills correctly. Important issue with bisphosphonates.    Important issue with bisphosphonates.    

► Persistence-Persistence- Still taking the pills. Still taking the pills. Often measured at the one year time point.Often measured at the one year time point.

Non-AdherenceNon-AdherenceHow Large is The Problem?How Large is The Problem?

Studies of patient behavior show that Studies of patient behavior show that LESS THAN 50%LESS THAN 50%

of the people who leave a doctor's of the people who leave a doctor's office with a prescriptionoffice with a prescription

adhere and comply with drug therapyadhere and comply with drug therapy

Simons, et al MJA 1996; 164:208.

n = 610

Persistence with Lipid-Lowering Persistence with Lipid-Lowering TherapyTherapy

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11

Months on lipid lowering therapy

% persisting

The Effects of Non-AdherenceThe Effects of Non-Adherence

1) Poor patient outcomes due to1) Poor patient outcomes due to sub-optimal therapeutic responsesub-optimal therapeutic response

2) Increased cost burden to society2) Increased cost burden to society

Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

Poor Patient OutcomesPoor Patient Outcomes

► Increased Morbidity due to disease Increased Morbidity due to disease “exacerbations” “exacerbations”

► More treatment “Failures” with potential for More treatment “Failures” with potential for addition or switching of medications due to addition or switching of medications due to perceived inefficacyperceived inefficacy

► More frequent Physician VisitsMore frequent Physician Visits► Increased HospitalizationsIncreased Hospitalizations► Excess MortalityExcess Mortality

Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

Costs To SocietyCosts To Society

► 10% excess in all hospital admissions10% excess in all hospital admissions

► 125,000 to 200,000 deaths per year125,000 to 200,000 deaths per year

► 50-100 Billion dollars excess cost per year 50-100 Billion dollars excess cost per year in the U.S.in the U.S.

Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

What Are the Possible Causes of What Are the Possible Causes of Poor Adherence?Poor Adherence?

Disruption to daily routine?

(need for frequent dosing)

Concern about side effects?

“Target disease" eclipsed by other

chronic conditions?

Lack of positive reinforcement?

Complex dosing

guidelines?

Poor patient education

(Health Illiteracy)

POORADHERENCE

Health Literacy

*(Selden et al. 2000; Healthy People 2010, HHS 2000; Ratzan & Parker 2000) **(Institute of Medicine report- 2004)

The degree to which individuals have the capacity to The degree to which individuals have the capacity to obtain, process, and understand basic information obtain, process, and understand basic information and make appropriate decisions about their health*and make appropriate decisions about their health*

90 million people in the United States, nearly half of 90 million people in the United States, nearly half of all adults, have difficulty understanding and using all adults, have difficulty understanding and using health information**health information**

Literacy Level Predicts Health OutcomesLiteracy Level Predicts Health Outcomes

► Less knowledge of disease and self-careLess knowledge of disease and self-care► Worse self-management skillsWorse self-management skills► Lower use of screeningLower use of screening► Lower medication compliance ratesLower medication compliance rates► Higher rates of hospitalization and morbidityHigher rates of hospitalization and morbidity► Literacy level is more important than racial Literacy level is more important than racial

or ethnic group, age, employment, income or ethnic group, age, employment, income or education in predicting poor outcomeor education in predicting poor outcome

Patient Beliefs Affect CompliancePatient Beliefs Affect Compliance

► Don’t believe diagnosis or the Don’t believe diagnosis or the seriousness of the diagnosisseriousness of the diagnosis

► Believe other diseases are more Believe other diseases are more importantimportant

► Believe side effects outweigh benefitsBelieve side effects outweigh benefits

► Concerned about their ability to carry out Concerned about their ability to carry out recommended actionrecommended action

AARP Survey, 1985National Prescription Buyers’ Survey, USA 1985

Lack of CommunicationLack of Communication

► Study of 300 medical encounters: doctors spent Study of 300 medical encounters: doctors spent average 1.3 minutes giving informationaverage 1.3 minutes giving information11

► Study of 264 visits to family physicians.-during Study of 264 visits to family physicians.-during patient initial statement of the problem, patient initial statement of the problem, physician interrupted after average of 23 physician interrupted after average of 23 seconds.seconds.22

► 50% of patients leave office visit not 50% of patients leave office visit not understanding what the doctor saidunderstanding what the doctor said33

Clement, Diab Care 1995;18:1204. Waitzkin. JAMA 1984;252:24411

Kravitz et al. Arch Intern Med 1993;153:1869. 2

Roter and Hall. Ann Rev Public Health 1989;10:163. Marvel JAMA 1999;281:283. 3

Physicians Contribute toPhysicians Contribute toPatients’ Poor Adherence By:Patients’ Poor Adherence By:

►Prescribing complex regimens Prescribing complex regimens ►Failing to explain the benefits and Failing to explain the benefits and

side effects of a medication side effects of a medication adequately adequately

►Not giving consideration to the Not giving consideration to the patient’s lifestyle or the cost of the patient’s lifestyle or the cost of the medications medications

Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

Nonadherence to Nonadherence to Osteoporosis Medications: Osteoporosis Medications:

How Common Is It? How Common Is It?

Adherence With Osteoporosis Adherence With Osteoporosis Medications Is Sub-optimalMedications Is Sub-optimal

Tosteson ANA, et al. Am J Med. 2003;115:209-216.

20% to 25% of Patients Abandon Therapy Within 7 Months20% to 25% of Patients Abandon Therapy Within 7 Months

Pat

ien

ts A

ban

do

nin

gT

reat

men

t (%

)

30

25

20

15

10

5

0 Hormone Replacement Therapy(n=334)

Bisphosphonate(n=366)

Selective Estrogen Receptor Modulator

(n=256)

Telephone survey of 956 randomly selected women with postmenopausal osteopenia or osteoporosis who initiated therapy in 2000-2001. Mean follow-up was 7 months.

26%

19% 19%

Ettinger M, et al. Arthritis Rheum. 2004;50(suppl):S513-S514. Abstract 1325.

A HIPAA-compliant, longitudinal patient database of prescriptions dispensed from ~25% of US retail pharmacies was used to assess discontinuation of bisphosphonates over a 12-month period in women aged ≥50 years.*

* Primary usage in osteoporosis; however, data may include use in other indications.

Adherence With Oral Bisphosphonates Is Adherence With Oral Bisphosphonates Is Suboptimal, Regardless of DosingSuboptimal, Regardless of Dosing

Percentage of Patients on Therapy (defined as having at least 1 day of medication supply in the month)

P<0.001 vs daily therapy

10

20

30

40

50

60

70

80

90

100

Oct2002

Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct2003

Pat

ien

ts o

n T

her

apy

(%)

Daily Bisphosphonates (n=33,767)

Weekly Bisphosphonates (n=177,552)

54.6%

36.9%

Surgeon General’s Report Cites Need toSurgeon General’s Report Cites Need toImprove Adherence With Osteoporosis TherapiesImprove Adherence With Osteoporosis Therapies

► Long-term adherence rates with Long-term adherence rates with any medication are poor (~50%)any medication are poor (~50%)

► Follow-up strategies that Follow-up strategies that improve adherence to should be improve adherence to should be applied to osteoporosisapplied to osteoporosis– Simplifying the treatment Simplifying the treatment

regimenregimen– Counseling Counseling – Addressing patient concerns Addressing patient concerns

about side effectsabout side effects– Maintaining an encouraging Maintaining an encouraging

provider-patient relationshipprovider-patient relationship

US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004.

Potential Consequences of Poor AdherencePotential Consequences of Poor Adherenceto Osteoporosis Therapyto Osteoporosis Therapy

►Poorer clinical outcomes Poorer clinical outcomes – Less effective suppression in the rate of Less effective suppression in the rate of

bone turnoverbone turnover11

– Lower gains or greater losses in bone Lower gains or greater losses in bone mineral densitymineral density1,21,2

– Greater risk of fracturesGreater risk of fractures33

►Higher medical costsHigher medical costs44

1. Eastell R, et al. Calcif Tissue Int. 2003;72:408. Abstract P-297. 2. Finigan J, et al. Osteoporos Int. 2001;12:S48-S49. Abstract P110. 3. Caro JJ, et al. Osteoporos Int. 2004;15:1003-1008.4. McCombs JS, et al. Maturitas. 2004;48:271-287.

Non-Adherence to OsteoporosisNon-Adherence to OsteoporosisMedication Affects BMDMedication Affects BMD

0

0.5

1

1.5

2

2.5

3

3.5

4

Compliant

Non-compliant

Yood R, et al Osteoporosis int 14:2003. 965-68

Lumbar Lumbar BMDBMD

Non-Adherence to OsteoporosisNon-Adherence to OsteoporosisMedication Increases Fracture RiskMedication Increases Fracture Risk

3.4

3.6

3.8

4

4.2

4.4

4.6

Non-compliant

Compliant

11,249 women suffering from osteoporosis with a mean age of 68.4 years and average follow-up of 2 years

16% decrease

Caro JJ et al. Osteoporosis Int 14, 2003, Suppl 7

Fracture Rate %

* P<0.0001.† Compliant is defined as taking medication ≥80% of the time over a 24-month period.

Retrospective cohort study that used longitudinal medical and pharmacy claims data from Medstat MarketScan® Research Databases to assess adherence and fracture risk over 24 months (1999-2003).

Siris E, et al. Presented at: Sixth International Symposium on Osteoporosis. April 6-10, 2005; Washington, DC.

Better Long-term Compliance ReducesBetter Long-term Compliance Reducesthe Risk of Fracturethe Risk of Fracture

Compliance With Bisphosphonates and Fracture Risk Over 2 Years in Women ≥45 Years With Postmenopausal Osteoporosis

(n=6825)

% P

atie

nts

Wit

h F

ract

ure

0

2

4

6

8

10

12

14

Compliant Noncompliant

(n=3400) (n=3425)

*

†

9.4%

12.6%

How Can Adherence How Can Adherence Be Improved?Be Improved?

Improving Adherence byImproving Adherence byReinforcing Treatment EfficacyReinforcing Treatment Efficacy

►Patient monitoring may be helpful Patient monitoring may be helpful in demonstrating effects of in demonstrating effects of treatmenttreatment1-31-3

– BMDBMD– Biochemical markers of bone Biochemical markers of bone

turnoverturnover

►Frequent visits or calls from staffFrequent visits or calls from staff

1. Clowes et al. JCEM. 2004;89:1117-1123).2. Deal CL. Curr Rheumatol Rep. 2001;3:233-239.3. Chapurlat RD, Cummings SR. Osteoporos Int. 2002;13:738-744.

Improving Adherence Through Modifying Dosing Improving Adherence Through Modifying Dosing Interval: Focus on BisphosphonatesInterval: Focus on Bisphosphonates

►Survey data suggests that patients Survey data suggests that patients prefer more widely-spaced dosing prefer more widely-spaced dosing intervalsintervals

►Retrospective data suggest improved Retrospective data suggest improved adherence with once-weekly versus adherence with once-weekly versus daily bisphosphonatesdaily bisphosphonates

►To date, there are no prospective data To date, there are no prospective data demonstrating that extended dosing demonstrating that extended dosing regimens improve patient adherence regimens improve patient adherence and clinical outcomesand clinical outcomes

Women Preferred Weekly over DailyWomen Preferred Weekly over Daily

►288 postmenopausal women with osteoporosis 288 postmenopausal women with osteoporosis – 4 weeks of alendronate Weekly followed by 4 weeks alendronate Daily4 weeks of alendronate Weekly followed by 4 weeks alendronate Daily– 4 weeks of alendronate Daily followed by 4 weeks alendronate Weekly4 weeks of alendronate Daily followed by 4 weeks alendronate Weekly

►At the final visit, patients completed a preference study At the final visit, patients completed a preference study questionnaire: Which Treatment Routine…questionnaire: Which Treatment Routine…

AlendronateAlendronate

Simon JA et al Clin Ther 2002;24:1871-1886

86.4% 89.0% 87.5%

9.2% 7.7% 8.5%4.4% 3.3% 4.0%

0

20

40

60

80

100

Once weekly

Once daily

No preference

Do You Prefer?Do You Prefer?

Pat

ien

ts (

%)

Pat

ien

ts (

%)

Is More Convenient?Is More Convenient? Would Be Easier toWould Be Easier toComply With For aComply With For a

Long Period of Time?Long Period of Time?

33%

Once a month Once a month

Once a week Once a week

Women Preferred Monthly over WeeklyWomen Preferred Monthly over Weekly

Dosing Schedule PreferenceDosing Schedule Preference(n = 367)*(n = 367)*

p <0.001p <0.001

** Among women expressing a preference, 67% prefer once-a-month dosing, Among women expressing a preference, 67% prefer once-a-month dosing, a statistically significantly higher proportion than the 33% who prefer once-a-week dosinga statistically significantly higher proportion than the 33% who prefer once-a-week dosing

Patients Say They Prefer a Once-a-month Patients Say They Prefer a Once-a-month Over a Once-a-week Dosing ScheduleOver a Once-a-week Dosing Schedule

67%

Simon JA et al Female Patient 2005;30:31-6

BALTO- Study DesignBALTO- Study Design

► A randomized, prospective, 6 month Phase IIIB, A randomized, prospective, 6 month Phase IIIB, open-label, multi-center, crossover study open-label, multi-center, crossover study

► Primary EndpointPrimary Endpoint – Proportion (%) of patients – Proportion (%) of patients preferring once-monthly dosing of ibandronate preferring once-monthly dosing of ibandronate over once-weekly dosing of alendronate over once-weekly dosing of alendronate

► Secondary EndpointSecondary Endpoint – Proportion (%) of – Proportion (%) of patients perceiving the once-monthly dosing of patients perceiving the once-monthly dosing of ibandronate to be more convenient versus ibandronate to be more convenient versus once-weekly dosing of alendronateonce-weekly dosing of alendronate

Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903

* p < 0.0001 vs alendronate* p < 0.0001 vs alendronate

Excludes those patients who did not express a preference for one treatment / m ITT populationExcludes those patients who did not express a preference for one treatment / m ITT population

Twenty-two patients did not express preferenceTwenty-two patients did not express preference

Patient Preference: Ibandronate MonthlyPatient Preference: Ibandronate Monthlyvs Alendronate Weeklyvs Alendronate Weekly

28.6%

71.4%*

0

10

20

30

40

50

60

70

80

Ibandronate Alendronate

Preferred TreatmentPreferred Treatment

Pat

ien

ts (

%)

Pat

ien

ts (

%)

n = 197 n = 79

Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903

(Patients Expressing Preference)(Patients Expressing Preference)

* p < 0.0001 vs alendronate* p < 0.0001 vs alendronate

Excludes those patients who did not express a preference for treatmentExcludes those patients who did not express a preference for treatment

Thirty-two patients found both treatments equally convenientThirty-two patients found both treatments equally convenient

25.4%

74.6%*

0

10

20

30

40

50

60

70

80

Ibandronate AlendronateMore Convenient TherapyMore Convenient Therapy

Pat

ien

ts (

%)

Pat

ien

ts (

%)

n = 197 n = 67

Patient Preference: Ibandronate MonthlyPatient Preference: Ibandronate Monthlyvs Alendronate Weeklyvs Alendronate Weekly

(Those Expressing Convenience)(Those Expressing Convenience)

Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903

Principles of Evidence-Based MedicinePrinciples of Evidence-Based Medicine

►AcquireAcquire the Evidence the Evidence

►Critically Critically AppraiseAppraise the Evidence the Evidence

►ApplyApply the Evidence to the Individual the Evidence to the Individual PatientPatient

Evidence-Based Medicine: Integrate Findings Evidence-Based Medicine: Integrate Findings With Clinical Expertise and Patient NeedsWith Clinical Expertise and Patient Needs

Clinical Expertise

Research Evidence

Patient Preferences

Rx

Adapted from: Sackett DL et al. Evidence-Based Medicine: How to Practice and Teach EBM. 2nd ed.

Churchill Livingstone; 2000

SummarySummary

► Adherence to daily and weekly bisphosphonates Adherence to daily and weekly bisphosphonates is suboptimalis suboptimal

► Poor adherence may compromise clinical Poor adherence may compromise clinical outcomes and may increase healthcare utilizationoutcomes and may increase healthcare utilization

► Need to improve communication and education of Need to improve communication and education of patients utilizing all available resourcespatients utilizing all available resources

► Among other factors, dosing frequency may be Among other factors, dosing frequency may be an important determinant of adherence with an important determinant of adherence with bisphosphonatesbisphosphonates

““Drugs don’t work in people that Drugs don’t work in people that don’t take them”don’t take them”

C. Everett Koop, M.D.C. Everett Koop, M.D.

Applying Evidence to Practice—Applying Evidence to Practice—Prevention and Treatment of Patients Prevention and Treatment of Patients

Suspected or Confirmed Osteoporosis:Suspected or Confirmed Osteoporosis:An Interactive Case Study ApproachAn Interactive Case Study Approach

Case Study # 1: Low BMD in An Early Case Study # 1: Low BMD in An Early Postmenopausal WomanPostmenopausal Woman

Case 1Case 1

► LR is a 52 year old newly menopausal white woman LR is a 52 year old newly menopausal white woman – She has hot flashes but no fractures orShe has hot flashes but no fractures or

height lossheight loss– She is of average height and weight (5’2”,She is of average height and weight (5’2”,

137 pounds)137 pounds)– She has an intact uterusShe has an intact uterus– There is no family history of OPThere is no family history of OP– She had never undergone BMD testingShe had never undergone BMD testing

However, you ordered a DXA which showed aHowever, you ordered a DXA which showed aT-score of -1.8 in lumbar spine and -1.5 in femoral neckT-score of -1.8 in lumbar spine and -1.5 in femoral neck

►Diagnosed as osteopeniaDiagnosed as osteopenia

►What would you do?What would you do?

►Would you treat with an Would you treat with an antiresorptive therapy?antiresorptive therapy?

Case 1Case 1

► With no history of fx or FH, her absolute risk for an With no history of fx or FH, her absolute risk for an osteoporotic spine, hip or wrist fx over the next 5 years is osteoporotic spine, hip or wrist fx over the next 5 years is very low at <0.12%/yvery low at <0.12%/y

► No utility for bone markers in this age groupNo utility for bone markers in this age group

► No treatments have been proven to reduce fx risk in women No treatments have been proven to reduce fx risk in women in their 50s with osteopenia, although several treatments in their 50s with osteopenia, although several treatments may reduce bone lossmay reduce bone loss

► Bisphosphonates or PTH although effective would probably Bisphosphonates or PTH although effective would probably be unjustified based on her low absolute risk and the high be unjustified based on her low absolute risk and the high NNT of 2000NNT of 2000

Case 1Case 1

► Consider preventive approachesConsider preventive approaches► At her age with a uterus she is more likely At her age with a uterus she is more likely

to have an AE from HRT (VTE, MI, breast to have an AE from HRT (VTE, MI, breast CA) than a beneficial outcomeCA) than a beneficial outcome

► Raloxifene is an optionRaloxifene is an option– May lower risk of breast caMay lower risk of breast ca– May aggravate hot flashesMay aggravate hot flashes

► Calcium and vitamin DCalcium and vitamin D

Case 1Case 1

Case 1: Case 1: What Mrs. LR Chose To Do…What Mrs. LR Chose To Do…

► Chose to decline any pharmacologic Chose to decline any pharmacologic intervention intervention

► Agreed to calcium supplementation 500mg Agreed to calcium supplementation 500mg bid, a MVI, and an exercise programbid, a MVI, and an exercise program

► Began to experiment with soy Began to experiment with soy preparationspreparations– No evidence that these agents reduce fx risk or No evidence that these agents reduce fx risk or

prevent bone lossprevent bone loss

Case 2. Case 2. A postmenopausal woman A postmenopausal woman who recently discontinued who recently discontinued

HRT but has low BMDHRT but has low BMD

► RG is a 68-year-old woman who has been RG is a 68-year-old woman who has been on HT since menopauseon HT since menopause– She initially took HT for hot flashes but She initially took HT for hot flashes but

continued when she was told of benefits for her continued when she was told of benefits for her heart and bonesheart and bones

– When she heard the WHI results she When she heard the WHI results she discontinued HTdiscontinued HT

► She has scheduled a visit with you to She has scheduled a visit with you to discuss whether she needs additional discuss whether she needs additional therapy to treat or prevent OPtherapy to treat or prevent OP

Case 2Case 2

Case 2: History Mrs. RGCase 2: History Mrs. RG

► Meds: no calcium or vitamin D supplementsMeds: no calcium or vitamin D supplements– She takes a MVIShe takes a MVI– She is lactose intolerantShe is lactose intolerant– She has lost 2 inches in heightShe has lost 2 inches in height

► Approximately 10 years ago she broke her Approximately 10 years ago she broke her forearm when she slipped on the sidewalkforearm when she slipped on the sidewalk

► No FH of OPNo FH of OP

► At age 65 she had a DXA which showed At age 65 she had a DXA which showed spine T-score of -2.0 and total hip T-score spine T-score of -2.0 and total hip T-score of -2.2of -2.2

► She has OP based on relatively low BMD She has OP based on relatively low BMD and history of fractureand history of fracture

► Her absolute risk of fracture in 5 years will Her absolute risk of fracture in 5 years will be high, assuming that HRT effects on be high, assuming that HRT effects on bone will diminish with timebone will diminish with time

Case 2: History Mrs. RGCase 2: History Mrs. RG

►Need to exclude secondary OPNeed to exclude secondary OP– Serum calciumSerum calcium– TSHTSH– 25 OH D25 OH D– 24 hour urinary calcium24 hour urinary calcium

Case 2Case 2

Case 2:Case 2:Medical Recommendations Mrs. RGMedical Recommendations Mrs. RG

►Calcium supplementation 1200 mgCalcium supplementation 1200 mg►800 IU vitamin D (her MVI has 400 IU)800 IU vitamin D (her MVI has 400 IU)►ExerciseExercise►Medication options:Medication options:

– Bisphosphonates weekly or monthlyBisphosphonates weekly or monthly– SERMSSERMS

►Follow-up BMD in two yearsFollow-up BMD in two years

Case 2: What Mrs. RG DidCase 2: What Mrs. RG Did

► Ibandronate 150 mg once monthlyIbandronate 150 mg once monthly►1000 mg calcium supplementation 1000 mg calcium supplementation ►400 IU vitamin D plus her MVI400 IU vitamin D plus her MVI

Case 3.Case 3.Severe postmenopausal Severe postmenopausal

osteoporosisosteoporosis

Case 3: Mrs. RWCase 3: Mrs. RW

► 70 year old woman with low BMD and multiple 70 year old woman with low BMD and multiple vertebral fractures who has been on a weekly vertebral fractures who has been on a weekly bisphosphonate, ca, vitamin D for two yearsbisphosphonate, ca, vitamin D for two years– Her lumbar spine T-score in Jan 2001 was -3.0Her lumbar spine T-score in Jan 2001 was -3.0– A repeat DXA today shows a lumbar spineA repeat DXA today shows a lumbar spine

T-score of -3.5, and a FN T-score of -3.0T-score of -3.5, and a FN T-score of -3.0– She has significant midback pain and has new OP fx of She has significant midback pain and has new OP fx of

the thoracic spine with significant deformitythe thoracic spine with significant deformity

► Vertebroplasty was recommended byVertebroplasty was recommended byher PCPher PCP

Case 3: MRI SeriesCase 3: MRI Series

T1 T2 T2 STIR

Case 3:Case 3:The Magnitude of the Loss is TroublesomeThe Magnitude of the Loss is Troublesome

Consider the following:Consider the following:► Is she a non-responder?Is she a non-responder?► Is she taking her bisphosphonate?Is she taking her bisphosphonate?► Is the bisphosphonate being absorbed?Is the bisphosphonate being absorbed?► Are there secondary causes of Are there secondary causes of

osteoporosis contributing to her bone osteoporosis contributing to her bone loss and fractures?loss and fractures?

► What therapeutic interventions both What therapeutic interventions both pharmacologic and nonpharmacologic pharmacologic and nonpharmacologic should we consider?should we consider?

Case 3: What Mrs. RW DidCase 3: What Mrs. RW Did

► Treated aggressively with opioidsTreated aggressively with opioids► Refused vertebral body augmentationRefused vertebral body augmentation► Initially switched to another oral bisphosphonate Initially switched to another oral bisphosphonate

but untx was high at 55but untx was high at 55► 25 OHD level 35 25 OHD level 35 ► Calcium supplementation to 1500 mg/dailyCalcium supplementation to 1500 mg/daily► Switched to ForteoSwitched to Forteo► Back pain diminishedBack pain diminished► 6% increase in lumbar spine BMD at 6 months6% increase in lumbar spine BMD at 6 months

Case 4.Case 4.Age related osteoporosisAge related osteoporosis

Case 4: Mrs. PRCase 4: Mrs. PR

► An 80-year-old frail, community dwelling woman An 80-year-old frail, community dwelling woman who lives alonewho lives alone– She has no hx of fx but falls often during the yearShe has no hx of fx but falls often during the year– She takes 1000 mg calcium daily and a MVIShe takes 1000 mg calcium daily and a MVI– She does not go out in the sunShe does not go out in the sun– She has difficulty walkingShe has difficulty walking– She has a long hx of GERDShe has a long hx of GERD– She has HBP treated with beta blockersShe has HBP treated with beta blockers– BMD T-score of -2.8 at hip and -2.0 in spineBMD T-score of -2.8 at hip and -2.0 in spine

Case 4:Case 4:Medical Recommendations Mrs. PRMedical Recommendations Mrs. PR

► Falls assessmentFalls assessment► Check vitamin DCheck vitamin D

– She had 25 OHD level of 8 ng/mlShe had 25 OHD level of 8 ng/ml– 50,000 U of oral vitamin D weekly for 3 months50,000 U of oral vitamin D weekly for 3 months

► Take calcium in divided dosesTake calcium in divided doses► Exercise programExercise program► Hip protectorsHip protectors► Her risk of NVF is high 10%/yearHer risk of NVF is high 10%/year► Started on a bisphosphonateStarted on a bisphosphonate

Case 4: What Mrs. PR DidCase 4: What Mrs. PR Did

►50,000 U ergocalciferol weekly for50,000 U ergocalciferol weekly for3 months3 months

►Chose weekly bisphosphonateChose weekly bisphosphonate►PT programPT program►She refused hip protectorsShe refused hip protectors

Clinical Risk FactorsClinical Risk Factors

Femoral neck T-score +Femoral neck T-score +► AgeAge

► Previous low trauma fracturePrevious low trauma fracture

► Current cigarette smokingCurrent cigarette smoking

► Rheumatoid arthritisRheumatoid arthritis

► High alcohol intake (> 2 units/day)High alcohol intake (> 2 units/day)

► Parental history of hip fractureParental history of hip fracture

► Prior or current glucocorticoid usePrior or current glucocorticoid use

Adapted from Kanis JA et al. Osteoporos Int. 2005;16:581-589.

Intervention ThresholdIntervention Threshold

►A fracture probability above which it A fracture probability above which it is is cost-effectivecost-effective to treat with to treat with pharmacological agentspharmacological agents

►Based on statistical modeling using Based on statistical modeling using many medical, social, and economic many medical, social, and economic assumptions assumptions

Case 5Case 5

Patient Case #5Patient Case #5

► 70 year old post menopausal female70 year old post menopausal female► Wrist fracture at age 62Wrist fracture at age 62► T-score lumbar spine = -0.8T-score lumbar spine = -0.8► T-score femoral neck and total hip = -1.5T-score femoral neck and total hip = -1.5► Should she receive pharmacological Should she receive pharmacological

therapy?therapy?► What would you choose and why? What would you choose and why? ► Would you choose a different therapy if her Would you choose a different therapy if her

T-score was –3.5?T-score was –3.5?

Case 6Case 6

►52 year old post menopausal female52 year old post menopausal female►Mother had hip fracture at age 69Mother had hip fracture at age 69►T-score lumbar spine = -1.5, femoral T-score lumbar spine = -1.5, femoral

neck -1.6neck -1.6►Should she receive pharmacological Should she receive pharmacological

therapy? therapy? ►Would bone markers help your Would bone markers help your

decision? decision?

Patient Case #6Patient Case #6

►What therapy would you choose?What therapy would you choose?– Hormone therapyHormone therapy– SERMSERM– Bisphosphonate- which one?Bisphosphonate- which one?

►She refuses pharmacological She refuses pharmacological therapy: she would like to try therapy: she would like to try calcium and vitamin D alonecalcium and vitamin D alone

►How and how often would you How and how often would you monitor her?monitor her?

Patient Case #6Patient Case #6

Case 7Case 7

►67 year old post menopausal female 67 year old post menopausal female with osteoporosiswith osteoporosis

►On risedronate 35 mg QW for 2 yearsOn risedronate 35 mg QW for 2 years

►Repeat DXA reveals 5% loss at the Repeat DXA reveals 5% loss at the spine and 4.5% loss at the total hipspine and 4.5% loss at the total hip

►What should you do?What should you do?

Patient Case #7Patient Case #7

►Her DXAs were performed at the same Her DXAs were performed at the same facility: her bone loss is statistically facility: her bone loss is statistically significant according to their precisionsignificant according to their precision

►She insists that she has taken her She insists that she has taken her bisphosphonate every week and has bisphosphonate every week and has followed proper administration followed proper administration instructionsinstructions

►What labs would you order?What labs would you order?

Patient Case #7Patient Case #7

► Her serum calcium, phosphorus, alkaline Her serum calcium, phosphorus, alkaline phosphatase, albumin and creatinine are phosphatase, albumin and creatinine are normalnormal

► 24 hour urine calcium = 175 mg24 hour urine calcium = 175 mg

► 25-OH vitamin D = 35 ng/ml25-OH vitamin D = 35 ng/ml

► Tissue transglutaminase- negativeTissue transglutaminase- negative

► Would you change her treatment?Would you change her treatment?

► What would you change her to?What would you change her to?

Patient Case #7Patient Case #7

Case 8Case 8

► A 66 year old female has a heel ultrasound A 66 year old female has a heel ultrasound

performed at a health fairperformed at a health fair

► Her T-score at the heel = -2.5Her T-score at the heel = -2.5

► Does she have osteoporosis?Does she have osteoporosis?

► What other tests, if any, should be What other tests, if any, should be

performed?performed?

Patient Case #8Patient Case #8

►A DXA reveals a T-score at the spine A DXA reveals a T-score at the spine of –2.7 and at he femoral neck of –1.9of –2.7 and at he femoral neck of –1.9

►Lab workup is negative except for a Lab workup is negative except for a 25-OH D level of 18 ng/ml25-OH D level of 18 ng/ml

►What therapy would you choose?What therapy would you choose?– Hormone therapyHormone therapy– SERMSERM– TeriparatideTeriparatide– Bisphosphonate- which one?Bisphosphonate- which one?

Patient Case #8Patient Case #8

Case 9Case 9

►67 year old postmenopausal female67 year old postmenopausal female►History: Heart disease, high cholesterol, History: Heart disease, high cholesterol,

hypertension and osteoporosishypertension and osteoporosis►She takes alendronate 70 mg QW for OPShe takes alendronate 70 mg QW for OP

– Complains about taking multiple pillsComplains about taking multiple pills– Often forgets to take her medicationsOften forgets to take her medications– Requests help in simplifying her Requests help in simplifying her

medication schedulesmedication schedulesWhat are some other options?What are some other options?

Patient Case #9Patient Case #9

►You offer her ibandronate 150 mg You offer her ibandronate 150 mg once-a-monthonce-a-month

►How can you help her remember to How can you help her remember to take her pill every month?take her pill every month?

►What other methods could you use What other methods could you use to re-inforce effectiveness of therapy to re-inforce effectiveness of therapy and persistence?and persistence?

Patient Case #9Patient Case #9

Clinical Risk FactorsClinical Risk Factors

Femoral neck T-scoreFemoral neck T-score + +

► AgeAge

► Previous low trauma fracturePrevious low trauma fracture

► Current cigarette smokingCurrent cigarette smoking

► Rheumatoid arthritisRheumatoid arthritis

► High alcohol intake (> 2 units/day)High alcohol intake (> 2 units/day)

► Parental history of hip fractureParental history of hip fracture

► Prior or current glucocorticoid usePrior or current glucocorticoid use

Adapted from Kanis JA et al. Osteoporos Int. 2005;16:581-589.

Intervention ThresholdIntervention Threshold

►A fracture probability above which A fracture probability above which it is it is cost-effectivecost-effective to treat with to treat with pharmacological agentspharmacological agents

►Based on statistical modeling using Based on statistical modeling using many medical, social, and many medical, social, and economic assumptions economic assumptions