European
Congress on
Osteoporosis and
Osteoarthritis
RATE OF OSTEOPOROTIC FRACTURE OVER
TIME AMONG WOMEN WITH AT LEAST ONE YEAR OF
ADHERENCE TO OSTEOPOROSIS THERAPY
Bordeaux, France
March 21-24, 2012
Ankita Modi1 , Jackson Tang 2, Shuvayu Sen1
1Global
Introduction
• Bisphosphonates such as alendronate, ibandronate, and
risendronate have shown proven efficacy in randomized clinical
trials for increasing bone mineral density (BMD) and reducing risk
of osteoporosis-related (fragility) fractures.1,2
• Poor adherence with osteoporosis treatment regimens is a wellrecognized problem, and the risk of having osteoporotic-related
fractures increases among patients with poor adherence.3,4
• However, fractures may be recorded even in patients who are
adherent to osteoporosis treatment.5,6
Objective
• To examine the rates of osteoporosis-related fractures over two
years of treatment among patients who were adherent to oral
bisphosphonates for at least one year.
Methods
Study design
• A retrospective cohort study using the i3 InVision Data Mart
(Ingenix, Eden Prairie, MN); a large U.S. claims database was
conducted.
• The study window was January 1, 2001 to December 31, 2010.
• The date of first prescription of an oral bisphosphonate during the
study window was the index date.
• There were three consecutive, one-year time periods during which
fracture rates were determined (Figure 1):
– Baseline period prior to the index date,
– Adherence period during which adherence with osteoporosis
treatment was calculated (Year 1 after index date),
– Study period (Year 2 after index date).
• Adherence with bisphosphonate treatment was defined as having
a medication possession ratio (MPR) of ≥0.6 during the adherence
period (MPR = total number of days’ supply/365 days).
• A MPR of > 0.8 for definition of adherence was also conducted as
a sensitivity analysis.
• Osteoporosis-related fractures included non-traumatic fractures
occurred at the hip, vertebral, and non-vertebral sites.7.8
• Osteoporosis-related fractures were identified by the ICD-9-CM
codes which were recorded in the primary and/or secondary
diagnoses in medical claims.
Data analysis
• The main analysis was conducted among patients who met the
study inclusion criteria and who were adherent (MPR > 0.6) in the
adherence period.
– A sensitivity analysis using adherence defined as MPR >= 0.8
was also conducted.
• The primary outcome was the frequency of osteoporotic fractures
during the baseline, adherence, and study period.
• The number of osteoporosis-related fractures was defined as the
total number of distinct fractures.
• History of fracture is defined as an occurrence of osteoporoticrelated fracture during the baseline or adherence period.
• Rate of osteoporotic-related fracture during the study period was
computed as number of osteoporotic fractures per 1,000 patient
years among adherent patients.
• Rate of osteoporotic-related fracture during the study period was
also compared between those with a history of fracture and those
without, and those who remained adherent in the study period
and those who did not.
Adherence period
(12-months)
Study period
(12-months)
MPR being calculated
Index Date
adherence
measured
Naive to all osteoporosis treatment
Study sample
• Included osteoporotic women 50 years or older whose first
osteoporosis treatment was an oral bisphosphonate from 20012010 and continuously enrolled for three consecutive years -- one
year before the index date and two years after the index date.
• Women were excluded if they had a diagnosis of malignant
neoplasm or a Paget's disease. (Figure 2).
• Oral bisphosphonate treatment included alendronate,
ibandronate, or risedronate. Medications were selected based on
National Drug codes.
Figure 2. Patient selection
Patients with osteoporosis diagnosis, fracture or treatment
N = 3,021,390
Patients whose first treatment is a bisphosphonate during study
window.
N = 845,091
Patients with at least 12-month continuous eligibility before and 24month of continuous eligibility after the index date
N = 106,105
Patients without Paget's disease or diagnoses of malignant neoplasm
N = 67,463
Women > 50 years of age as of index date
N = 62,446
Patients who were adherent
Patients who were non-adherent
N = 35,737 (57%)
N = 26,709 (43%)
Table 2. Percentage of patients with osteoporotic fractures
in the Baseline, adherence, and Study periodsA
Experienced fractures
Hip
Vertebral
Non-vertebral
Rib
Clavicle, scapula, and
sternum
Pelvis
Humerus
Forearm
Femur
Tibia and fibula
Number of distinct fractures
1
2
3
≥4
Number of distinct fracture
sites
1
2
3
A Values
Results
Characteristic
Adherent patients
(N=35,737)
Age at index date (years), mean (SD)
60.7 (8.5)
50-59
19,883 (55.6)
60-69
10,023 (28.0)
70-79
3,853 (10.8)
≥80
1,978 (5.5)
Charlson index, mean (SD)
0.37 (0.82)
Comorbidities 9
Chronic inflammatory bowel disease
284 (0.8)
Chronic inflammatory joint disease
5,142 (14.4)
Diabetes
2,411 (6.8)
Depression
1,636 (4.6)
Chronic kidney disease
206 (0.6)
Hypertension
10.948 (30.6)
____________________________________________________________
A Values are presented as N (%) unless otherwise indicated.
Percent patients with fractures in the Baseline,
adherence, and Study periods
• Osteoporotic-related fractures were recorded in the baseline,
adherence, and study periods for 1,507 (4.2%), 1,397 (3.9%), and
1,173 (3.3%) patients . The fracture rate during the study period
was 52/1000 patient-years. (Table 2)
• Vertebral and other non-vertebral fractures were most common,
representing over two thirds of all fractures during each of the
three periods. (Table 2)
Fracture rates during the study period by history
of fracture or by adherence in the study period
• Patients with a history of fracture experienced a higher rate of
fracture during the study period (18.0%) compared to those
without (2.2%). (Table 3)
• For the 24,342 (68.1%) patients who remained adherent for 2
years (in the adherence and study period), 784 (3.2%)
experienced osteoporotic-related fractures during the study
period. (Table 3)
• The fracture rate during the study period was 3.2% among those
who remained adherent and 3.4 % among those who didn’t.
(Table 3)
• A sensitivity analysis using MPR > 0.8 as a definition of adherence
yielded similar results, indicating that robustness of the definition
and study results.
adherence period
1,397 (3.9)
218 (0.6)
391 (1.1)
919 (2.6)
126 (0.4)
Study period
1,173 (3.3)
171 (0.5)
312 (0.9)
821 (2.3)
148 (0.4)
33 (0.1)
104 (0.3)
185 (0.5)
378 (1.1)
105 (0.3)
169 (0.5)
34 (0.1)
84 (0.2)
147 (0.4)
357 (1.0)
82 (0.2)
162 (0.5)
43 (0.1)
69 (0.2)
124 (0.4)
315 (0.9)
80 (0.2)
129 (0.4)
1,007 (2.8)
303 (0.9)
115 (0.3)
82 (0.2)
853 (2.4)
302 (0.9)
132 (0.4)
110 (0.3)
783 (2.2)
242 (0.7)
84 (0.2)
64 (0.2)
1,329 (3.7)
165 (0.5)
13 (0.0)
1,273 (3.6)
117 (0.3)
7 (0.0)
1,054 (3.0)
107 (0.3)
12 (0.0)
Table 3. Fracture rates in the Study period by fracture
history and by adherence in the Study periodA
Definition of adherence
MPR > 0.6
MPR > 0.8
(Main analysis)
(Sensitivity analysis)
Fracture history
Fracture history
All
All
Yes
No
Yes
No
Patient characteristics
• Of the 62,446 women who met eligibility criteria, 35,737 (57%)
were compliant to osteoporosis therapy during year 2 with mean
[SD] age of 60.7 [8.5] years). (Table 1)
• Hypertension (30.6%), chronic inflammatory joint disease (14.4%),
and fatigue (12.8%) were the most common comorbidities.
(Table 1)
Baseline period
1,507 (4.2)
265 (0.7)
459 (1.3)
974 (2.7)
132 (0.4)
are presented as N (%) unless otherwise indicated.
Study period
outcomes
Table 1. Patient characteristics in the Baseline period A
Figure 1. Study time periods
Baseline period
(12-months)
Health Outcomes, Merck & Company 2AsclepiusJT LLC
Number of patients
35,737
(100)
2,350
(6.6)
33,387
(93.4)
26,852
(100)
1,776
(6.6)
25,076
(93.4)
Number of patients
with osteoporoticrelated fracture
1,173
(3.3)
423
(18.0)
750
(2.2)
871
(3.2)
319
(18.0)
552
(2.2)
Number of fractures
1,851
737
1,114
1,389
556
833
52
314
33
52
313
33
Number of
fractures/1,000
patient-years
All
Compliant for
another year (study
period)
Yes
No
All
Compliant for
another year
(study period)
Yes
No
Number of patients
35,737
(100)
24,342
(68.1)
11,395
(31.9)
26,852
(100)
14,364
(53.5)
12,488
(46.5)
Number of patients
with osteoporoticrelated fracture
1,173
(3.3)
784
(3.2)
389
(3.4)
871
(3.2)
457
(3.2)
414
(3.3)
Number of fractures
1851
1,233
618
1389
700
689
52
51
54
52
49
55
Number of
fractures/1,000
patient-years
A Values
are presented as N (%) unless otherwise indicated.
Conclusions
• Among women 50 years and over on treatment with oral
bisphosphonates, 3.9% experienced an osteoporotic-related fracture
while being compliant to bisphosphonate treatment.
• Despite being compliant to bisphosphonate treatment for one year,
3.3% of patients experienced a fracture in the subsequent year.
• Additional interventions may be needed to manage osteoporosis in
adherent patients who may not be well controlled with current
therapies.
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