Transcript Management of Vertebral Compression Fractures

Screen & Intervene
Critical Challenges in Osteoporosis
and Women’s Health
Critical Challenges in Osteoporosis
Prevention and Treatment
Completing the Journey From Trial- and
Expert-Based Information to Clinical Application
in The Primary Care Setting
Critical Challenges in Osteoporosis
Prevention and Treatment
What Have We Learned Thus Far—A Summary
► Osteoporosis-An
Undertreated
Condition
► Complications of Osteoporotic
Fractures
► Indications for Screening
► Interpretation of BMD Measurements
► Aggregate Analysis of Risk Factors
Critical Challenges in Osteoporosis
Prevention and Treatment
What Have We Learned Thus Far—A Summary
► Treatment
Indications and Triggers
► Pharmacological Therapy for Fracture
Prevention
► Relationship between BMD changes and
Vertebral/Nonvertebral Fractures
► Vertebral and Nonvertebral Fracture
Prevention
► We will now discuss Adherence/Compliance,
and Their Relationship to Outcomes
Definitions
►
Initiation- Getting the prescription filled.
About 10% of prescriptions are never
filled.
► Adherence- Taking the medicine.
Often defined as taking more than 80% of
pills over a specified period of time.
► Compliance- Taking the pills correctly.
Important issue with bisphosphonates.
► Persistence- Still taking the pills.
Often measured at the one year time point.
Non-Adherence
How Large is The Problem?
Studies of patient behavior show that
LESS THAN 50%
of the people who leave a doctor's
office with a prescription
adhere and comply with drug therapy
Persistence with Lipid-Lowering
Therapy
100
90
% persisting
80
70
60
50
n = 610
40
30
20
10
0
0
1
2
3
4
5
6
7
8
Months on lipid lowering therapy
Simons, et al MJA 1996; 164:208.
9
10
11
The Effects of Non-Adherence
1) Poor patient outcomes due to
sub-optimal therapeutic response
2) Increased cost burden to society
Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97
Poor Patient Outcomes
► Increased
Morbidity due to disease
“exacerbations”
► More treatment “Failures” with potential for
addition or switching of medications due to
perceived inefficacy
► More frequent Physician Visits
► Increased Hospitalizations
► Excess Mortality
Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97
Costs To Society
► 10%
excess in all hospital admissions
► 125,000
to 200,000 deaths per year
► 50-100
Billion dollars excess cost per year
in the U.S.
Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97
What Are the Possible Causes of
Poor Adherence?
“Target disease"
eclipsed by other
chronic
conditions?
Lack of positive
reinforcement?
Complex
dosing
guidelines?
POOR
ADHERENCE
Concern about
side effects?
Poor patient
education
(Health
Illiteracy)
Disruption to
daily routine?
(need for frequent
dosing)
Health Literacy
The degree to which individuals have the capacity to
obtain, process, and understand basic information
and make appropriate decisions about their health*
90 million people in the United States, nearly half of
all adults, have difficulty understanding and using
health information**
*(Selden et al. 2000; Healthy People 2010, HHS 2000; Ratzan & Parker 2000)
**(Institute of Medicine report- 2004)
Literacy Level Predicts Health Outcomes
► Less
knowledge of disease and self-care
► Worse self-management skills
► Lower use of screening
► Lower medication compliance rates
► Higher rates of hospitalization and
morbidity
► Literacy level is more important than racial
or ethnic group, age, employment, income
or education in predicting poor outcome
Patient Beliefs Affect Compliance
► Don’t
believe diagnosis or the
seriousness of the diagnosis
► Believe
other diseases are more
important
► Believe
side effects outweigh benefits
► Concerned
about their ability to carry out
recommended action
AARP Survey, 1985
National Prescription Buyers’ Survey, USA 1985
Lack of Communication
► Study
of 300 medical encounters: doctors
spent average 1.3 minutes giving
information1
► Study
of 264 visits to family physicians.during patient initial statement of the
problem, physician interrupted after
average of 23 seconds.2
► 50%
of patients leave office visit not
understanding what the doctor said3
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 to
Patients’ Poor Adherence By:
► Prescribing
complex regimens
► Failing to explain the benefits and
side effects of a medication
adequately
► Not giving consideration to the
patient’s lifestyle or the cost of the
medications
Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97
Nonadherence to
Osteoporosis Medications:
How Common Is It?
Adherence With Osteoporosis
Medications Is Sub-optimal
Patients Abandoning
Treatment (%)
30
25
20% to 25% of Patients Abandon Therapy Within 7 Months
26%
20
19%
19%
Bisphosphonate
(n=366)
Selective Estrogen
Receptor Modulator
(n=256)
15
10
5
0
Hormone Replacement
Therapy
(n=334)
Telephone survey of 956 randomly selected women with postmenopausal osteopenia or osteoporosis
initiated therapy in 2000-2001. Mean follow-up was 7 months.
Tosteson ANA, et al. Am J Med. 2003;115:209-216.
who
Adherence With Oral Bisphosphonates Is
Suboptimal, Regardless of Dosing
Patients on Therapy (%)
100
Percentage of Patients on Therapy
(defined as having at least 1 day of medication supply in the month)
90
80
70
60
54.6%
50
40
36.9%
30
Weekly Bisphosphonates (n=177,552)
20
P<0.001 vs
daily therapy
Daily Bisphosphonates (n=33,767)
10
Oct Nov
Dec Jan Feb
Mar
Apr May Jun
Jul
Aug Sep Oct
2002
2003
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.
Ettinger M, et al. Arthritis Rheum. 2004;50(suppl):S513-S514. Abstract 1325.
Surgeon General’s Report Cites Need to
Improve Adherence With Osteoporosis Therapies
►
►
Long-term adherence rates with
any medication are poor (~50%)
Follow-up strategies that
improve adherence to should be
applied to osteoporosis
– Simplifying the treatment
regimen
– Counseling
– Addressing patient concerns
about side effects
– Maintaining an encouraging
provider-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 Adherence
to Osteoporosis Therapy
► Poorer
clinical outcomes
► Higher
medical costs4
– Less effective suppression in the rate of
bone turnover1
– Lower gains or greater losses in bone
mineral density1,2
– Greater risk of fractures3
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 Osteoporosis
Medication Affects BMD
4
3.5
3
Lumbar
BMD
2.5
2
1.5
1
0.5
0
Yood R, et al Osteoporosis int 14:2003. 965-68
Compliant
Non-compliant
Non-Adherence to Osteoporosis
Medication Increases Fracture Risk
11,249 women suffering from osteoporosis with a mean age of
68.4 years and average follow-up of 2 years
Fracture
Rate %
16% decrease
Caro JJ et al. Osteoporosis Int 14, 2003, Suppl 7
Better Long-term Compliance Reduces
the Risk of Fracture
Compliance With Bisphosphonates and Fracture Risk Over 2 Years
in Women ≥45 Years With Postmenopausal Osteoporosis
(n=6825)
% Patients With Fracture
12.6%
14
*
9.4%
12
10
8
6
4
2
0
†
Compliant
(n=3400)
Noncompliant
(n=3425)
* 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.
How Can Adherence
Be Improved?
Improving Adherence by
Reinforcing Treatment Efficacy
►Patient
monitoring may be helpful
in demonstrating effects of
treatment1-3
– BMD
– Biochemical markers of bone
turnover
►Frequent
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
Interval: Focus on Bisphosphonates
► Survey
data suggests that patients
prefer more widely-spaced dosing
intervals
► Retrospective data suggest improved
adherence with once-weekly versus
daily bisphosphonates
► To date, there are no prospective data
demonstrating that extended dosing
regimens improve patient adherence
and clinical outcomes
Women Preferred Weekly over Daily
Alendronate
► 288
postmenopausal women with osteoporosis
– 4 weeks of alendronate Weekly followed by 4 weeks alendronate Daily
– 4 weeks of alendronate Daily followed by 4 weeks alendronate Weekly
► At
the final visit, patients completed a preference study
questionnaire: Which Treatment Routine…
100
89.0%
86.4%
87.5%
Once weekly
Patients (%)
80
Once daily
60
No preference
40
20
9.2%
7.7%
4.4%
3.3%
8.5%
4.0%
0
Do You Prefer?
Is More Convenient?
Simon JA et al Clin Ther 2002;24:1871-1886
Would Be Easier to
Comply With For a
Long Period of Time?
Women Preferred Monthly over Weekly
Patients Say They Prefer a Once-a-month
Over a Once-a-week Dosing Schedule
Dosing Schedule Preference
(n = 367)*
Once a week
33%
67%
Once a month
p <0.001
* Among women expressing a preference, 67% prefer once-a-month dosing,
a statistically significantly higher proportion than the 33% who prefer once-a-week dosing
Simon JA et al Female Patient 2005;30:31-6
BALTO- Study Design
►
A randomized, prospective, 6 month Phase IIIB,
open-label, multi-center, crossover study
Primary Endpoint – Proportion (%) of patients
preferring once-monthly dosing of ibandronate
over once-weekly dosing of alendronate
► Secondary Endpoint – Proportion (%) of
patients perceiving the once-monthly dosing of
ibandronate to be more convenient versus
once-weekly dosing of alendronate
►
Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903
Patient Preference: Ibandronate Monthly
vs Alendronate Weekly
(Patients Expressing Preference)
80
71.4%*
Patients (%)
70
60
50
40
28.6%
30
20
10
0
n = 197
n = 79
Ibandronate
Alendronate
Preferred Treatment
* p < 0.0001 vs alendronate
Excludes those patients who did not express a preference for one treatment / m ITT population
Twenty-two patients did not express preference
Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903
Patient Preference: Ibandronate Monthly
vs Alendronate Weekly
(Those Expressing Convenience)
Patients (%)
80
74.6%*
70
60
50
40
25.4%
30
20
10
n = 197
n = 67
0
Ibandronate
Alendronate
More Convenient Therapy
* p < 0.0001 vs alendronate
Excludes those patients who did not express a preference for treatment
Thirty-two patients found both treatments equally convenient
Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903
Principles of Evidence-Based Medicine
► Acquire
the Evidence
► Critically Appraise
► Apply
the Evidence
the Evidence to the Individual
Patient
Evidence-Based Medicine: Integrate Findings
With Clinical Expertise and Patient Needs
Clinical
Expertise
Rx
Research
Evidence
Patient
Preferences
Adapted from: Sackett DL et al. Evidence-Based Medicine: How to Practice and Teach EBM. 2nd ed.
Churchill Livingstone; 2000
Summary
►
Adherence to daily and weekly bisphosphonates
is suboptimal
►
Poor adherence may compromise clinical
outcomes and may increase healthcare utilization
►
Need to improve communication and education of
patients utilizing all available resources
►
Among other factors, dosing frequency may be
an important determinant of adherence with
bisphosphonates
“Drugs don’t work in people that
don’t take them”
C. Everett Koop, M.D.
Applying Evidence to Practice—
Prevention and Treatment of Patients
Suspected or Confirmed Osteoporosis:
An Interactive Case Study Approach
Case Study # 1: Low BMD in An Early
Postmenopausal Woman
Case 1
►
LR is a 52 year old newly menopausal white woman
– She has hot flashes but no fractures or
height loss
– She is of average height and weight (5’2”,
137 pounds)
– She has an intact uterus
– There is no family history of OP
– She had never undergone BMD testing
However, you ordered a DXA which showed a
T-score of -1.8 in lumbar spine and -1.5 in femoral neck
Case 1
► Diagnosed
► What
as osteopenia
would you do?
► Would
you treat with an
antiresorptive therapy?
Case 1
►
With no history of fx or FH, her absolute risk for an
osteoporotic spine, hip or wrist fx over the next 5 years is
very low at <0.12%/y
►
No utility for bone markers in this age group
►
No treatments have been proven to reduce fx risk in women
in their 50s with osteopenia, although several treatments
may reduce bone loss
►
Bisphosphonates or PTH although effective would probably
be unjustified based on her low absolute risk and the high
NNT of 2000
Case 1
► Consider
preventive approaches
► At her age with a uterus she is more likely
to have an AE from HRT (VTE, MI, breast
CA) than a beneficial outcome
► Raloxifene is an option
– May lower risk of breast ca
– May aggravate hot flashes
► Calcium
and vitamin D
Case 1:
What Mrs. LR Chose To Do…
► Chose
to decline any pharmacologic
intervention
► Agreed to calcium supplementation
500mg bid, a MVI, and an exercise
program
► Began to experiment with soy
preparations
– No evidence that these agents reduce fx risk or
prevent bone loss
Case 2.
A postmenopausal woman
who recently discontinued
HRT but has low BMD
Case 2
► RG
is a 68-year-old woman who has been
on HT since menopause
– She initially took HT for hot flashes but
continued when she was told of benefits for her
heart and bones
– When she heard the WHI results she
discontinued HT
► She
has scheduled a visit with you to
discuss whether she needs additional
therapy to treat or prevent OP
Case 2: History Mrs. RG
► Meds:
no calcium or vitamin D supplements
– She takes a MVI
– She is lactose intolerant
– She has lost 2 inches in height
► Approximately
10 years ago she broke her
forearm when she slipped on the sidewalk
► No FH of OP
Case 2: History Mrs. RG
► At
age 65 she had a DXA which showed
spine T-score of -2.0 and total hip T-score
of -2.2
► She has OP based on relatively low BMD
and history of fracture
► Her absolute risk of fracture in 5 years will
be high, assuming that HRT effects on
bone will diminish with time
Case 2
► Need
to exclude secondary OP
– Serum calcium
– TSH
– 25 OH D
– 24 hour urinary calcium
Case 2:
Medical Recommendations Mrs. RG
► Calcium
supplementation 1200 mg
► 800 IU vitamin D (her MVI has 400 IU)
► Exercise
► Medication options:
– Bisphosphonates weekly or monthly
– SERMS
► Follow-up
BMD in two years
Case 2: What Mrs. RG Did
► Ibandronate
150 mg once monthly
► 1000 mg calcium supplementation
► 400 IU vitamin D plus her MVI
Case 3.
Severe postmenopausal
osteoporosis
Case 3: Mrs. RW
►
70 year old woman with low BMD and multiple
vertebral fractures who has been on a weekly
bisphosphonate, ca, vitamin D for two years
– Her lumbar spine T-score in Jan 2001 was -3.0
– A repeat DXA today shows a lumbar spine
T-score of -3.5, and a FN T-score of -3.0
– She has significant midback pain and has new OP fx of
the thoracic spine with significant deformity
►
Vertebroplasty was recommended by
her PCP
Case 3: MRI Series
T1
T2
T2 STIR
Case 3:
The Magnitude of the Loss is Troublesome
Consider the following:
► Is she a non-responder?
► Is she taking her bisphosphonate?
► Is the bisphosphonate being absorbed?
► Are there secondary causes of
osteoporosis contributing to her bone
loss and fractures?
► What therapeutic interventions both
pharmacologic and nonpharmacologic
should we consider?
Case 3: What Mrs. RW Did
►
►
►
►
►
►
►
►
Treated aggressively with opioids
Refused vertebral body augmentation
Initially switched to another oral bisphosphonate
but untx was high at 55
25 OHD level 35
Calcium supplementation to 1500 mg/daily
Switched to Forteo
Back pain diminished
6% increase in lumbar spine BMD at 6 months
Case 4.
Age related osteoporosis
Case 4: Mrs. PR
►
An 80-year-old frail, community dwelling woman who
lives alone
–
–
–
–
–
–
–
She has no hx of fx but falls often during the year
She takes 1000 mg calcium daily and a MVI
She does not go out in the sun
She has difficulty walking
She has a long hx of GERD
She has HBP treated with beta blockers
BMD T-score of -2.8 at hip and -2.0 in spine
Case 4:
Medical Recommendations Mrs. PR
►
►
Falls assessment
Check vitamin D
– She had 25 OHD level of 8 ng/ml
– 50,000 U of oral vitamin D weekly for 3 months
►
Take calcium in divided doses
► Exercise program
► Hip protectors
► Her risk of NVF is high 10%/year
► Started on a bisphosphonate
Case 4: What Mrs. PR Did
► 50,000
U ergocalciferol weekly for
3 months
► Chose weekly bisphosphonate
► PT program
► She refused hip protectors
Clinical Risk Factors
Femoral neck T-score +
►
Age
►
Previous low trauma fracture
►
Current cigarette smoking
►
Rheumatoid arthritis
►
High alcohol intake (> 2 units/day)
►
Parental history of hip fracture
►
Prior or current glucocorticoid use
Adapted from Kanis JA et al. Osteoporos Int. 2005;16:581-589.
Intervention Threshold
►A
fracture probability above which it
is cost-effective to treat with
pharmacological agents
► Based
on statistical modeling using
many medical, social, and economic
assumptions
Case 5
Patient Case #5
► 70
year old post menopausal female
► Wrist fracture at age 62
► T-score lumbar spine = -0.8
► T-score femoral neck and total hip = -1.5
► Should she receive pharmacological
therapy?
► What would you choose and why?
► Would you choose a different therapy if her
T-score was –3.5?
Case 6
Patient Case #6
► 52
year old post menopausal female
► Mother had hip fracture at age 69
► T-score lumbar spine = -1.5, femoral
neck -1.6
► Should she receive pharmacological
therapy?
► Would bone markers help your
decision?
Patient Case #6
► What
therapy would you choose?
– Hormone therapy
– SERM
– Bisphosphonate- which one?
► She
refuses pharmacological
therapy: she would like to try
calcium and vitamin D alone
► How and how often would you
monitor her?
Case 7
Patient Case #7
► 67
year old post menopausal female
with osteoporosis
► On
risedronate 35 mg QW for 2 years
► Repeat
DXA reveals 5% loss at the
spine and 4.5% loss at the total hip
► What
should you do?
Patient Case #7
► Her
DXAs were performed at the same
facility: her bone loss is statistically
significant according to their precision
► She
insists that she has taken her
bisphosphonate every week and has
followed proper administration
instructions
► What
labs would you order?
Patient Case #7
► Her
serum calcium, phosphorus, alkaline
phosphatase, albumin and creatinine are
normal
► 24
hour urine calcium = 175 mg
► 25-OH
vitamin D = 35 ng/ml
► Tissue
transglutaminase- negative
► Would
you change her treatment?
► What
would you change her to?
Case 8
Patient Case #8
►A
66 year old female has a heel ultrasound
performed at a health fair
► Her
T-score at the heel = -2.5
► Does
she have osteoporosis?
► What
other tests, if any, should be
performed?
Patient Case #8
►A
DXA reveals a T-score at the spine
of –2.7 and at he femoral neck of –1.9
► Lab workup is negative except for a
25-OH D level of 18 ng/ml
► What therapy would you choose?
– Hormone therapy
– SERM
– Teriparatide
– Bisphosphonate- which one?
Case 9
Patient Case #9
► 67
year old postmenopausal female
► History: Heart disease, high
cholesterol, hypertension and
osteoporosis
► She takes alendronate 70 mg QW for
OP
– Complains about taking multiple pills
– Often forgets to take her medications
– Requests help in simplifying her
medication schedules
What are some other options?
Patient Case #9
► You
offer her ibandronate 150 mg
once-a-month
► How can you help her remember to
take her pill every month?
► What other methods could you use
to re-inforce effectiveness of therapy
and persistence?
Clinical Risk Factors
Femoral neck T-score +
►
Age
►
Previous low trauma fracture
►
Current cigarette smoking
►
Rheumatoid arthritis
►
High alcohol intake (> 2 units/day)
►
Parental history of hip fracture
►
Prior or current glucocorticoid use
Adapted from Kanis JA et al. Osteoporos Int. 2005;16:581-589.
Intervention Threshold
►A
fracture probability above which it
is cost-effective to treat with
pharmacological agents
► Based
on statistical modeling using
many medical, social, and
economic assumptions