Replication of the VERO Osteoporosis Trial in Healthcare Claims Data
Conditions: Osteoporosis
Sponsor: Brigham and Women's Hospital

Effects of teriparatide and risedronate on new fractures in post-menopausal 
women with severe osteoporosis (VERO): a multicentre, double-blind, double-
dummy, randomised controlled trial  (VERtebral fracture treatment comparisons in 
Osteoporotic women, VERO trial) 
DUPLICATE VERO
April 30, 2021 
NCT01709110 

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1. RCT Details 
This section provides a high-level overview of a published RCT that the described real-world evidence study is trying to replicate 
as closely as possible given the remaining limitations inherent in the healthcare databases. 
 
1.1 Title 
Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis 
(VERO): a multicentre, double-blind, double-dummy, randomised controlled trial (VERtebral fracture treatment 
comparisons in Osteoporotic women, VERO trial - NCT01709110) 
 
1.2 Intended aim(s) 
To assess the effects of 24 months of treatment with teriparatide compared with risedronate on the incidence of new fractures 
in post-menopausal women with preexisting vertebral fractures, regardless of previous osteoporosis treatment.  
 
1.3 Primary endpoint for replication  
New vertebral fracture. 
 
1.4 Required power for primary endpoint and noninferiority margin (if applicable) 
Assuming a 24-month new vertebral fracture incidence of 4.5% in the teriparatide group and 10% in the risedronate group, 
466 patients per group would provide 90% power to detect a difference between groups in the incidence of 
new vertebral fractures using a Pearson χ² test (two-sided α of 0.05). 
 
1.5 Secondary endpoint for replication (assay sensitivity) and RCT finding 
Non-vertebral fracture. 
 
1.6 Trial estimate 
Hazard Ratio, HR = 0.44 (95% CI, 0.29 to 0.68) comparing teriparatide vs. risedronate group during a 24-month period 
(Kendler et al., 2007).  
 
 
 
 
 
 

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2. Person responsible for implementation of replication in Aetion 
Elvira D’Andrea, MD, MPH, implemented the study design in the Aetion Evidence Platform. She is not responsible for the validity of 
the design and analytic choices. All implementation steps are recorded, and the implementation history is archived in the platform. 
 
3. Data Source(s) 
Optum CDM, IBM® MarketScan® 
 
4. Study Design Diagram 
The study design diagram visualizes key aspects of the longitudinal study design for expedited review. 
 
Figure 1. Design Diagram – VERO TRIAL REPLICATION 

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5. Cohort Identification  
 
5.1 Cohort Summary 
This study will involve a new user, parallel group, propensity score-matched, retrospective cohort design comparing injectable 
subcutaneous teriparatide (20 μg daily) to oral risedronate (35 mg weekly). The patients will be required to have continuous 
enrollment during a baseline period of 365 days before initiation of teriparatide or oral risedronate. We will restrict the analyses to 
women older than 45 with osteoporosis and history of vertebral fractures. 
 
5.2 Important steps for cohort formation 
New use of teriparatide (exposure) is defined as no use of the exposure drug within the 730 days (2 years) prior to index date. This 
will emulate the trial requirement for which treatment with teriparatide was not allowed any time before randomization. New use 
of risedronate (comparator) is defined as no use of the comparator drug within the 180 days prior to index date. The shorter 
washout period for risedronate users, compared to teriparatide users, will emulate the trial requirement of discontinuation of 
risedronate at the beginning of the screening period. Differently from teriparatide, history of risedronate use was allowed in the 
trial. New users of teriparatide are not allowed to receive risedronate within the 180 days prior to index date, and new users of 
risedronate are not allowed to receive teriparatide within the 730 days (2 years) prior to index date. 
 
5.2.1 Eligible cohort entry dates 
Teriparatide indication for treatment of osteoporosis in postmenopausal women was approved by FDA on Nov 26, 2002 
(the approval of risedronate for the same indication was antecedent to 2002). The initial eligible cohort entry date was the 
first date after Nov 26, 2002 commonly available in both the databases investigated (IBM® MarketScan®, Optum CDM). 
The last date eligible as cohort entry date was the end of available data for IBM® MarketScan®. For Optum CDM, we 
excluded the data cut that overlaps with the COVID-19 pandemic (range: April 1st - Jun 30th, 2020), since we assumed a 
higher proportion of drug discontinuation in that time period. The following eligible cohort entry dates were included: 
• IBM® MarketScan®: Jan 1, 2004 (start of available data) – December 31, 2018 (end of available data)  
• Optum CDM: Jan 1, 2004 (start of available data) – Mar 31, 2020  
 
5.2.2 Specify inclusion/exclusion criteria for cohort entry and define the index date 
Inclusion and exclusion criteria were adapted from the trial as closely as possible. Definitions for all inclusion/exclusion are 
provided in Appendix A and are summarized in the flowcharts below.  
 
5.3 Flowchart of the study cohort assembly 
For teriparatide vs. risedronate 

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Optum CDM 
IBM® MarketScan® 
  
Excluded 
Patients 
Remaining 
Patients 
Excluded 
Patients 
Remaining 
Patients 
All patients 
  
78202636 
  
200203908 
Did not meet cohort entry criteria 
-77830806 
371830 
-199450502 
753406 
Excluded due to insufficient enrollment 
-90897 
280933 
-176733 
576673 
Excluded due to prior use of referent 
-199055 
81878 
-403827 
172846 
Excluded due to prior use of exposure 
-19897 
61981 
-44254 
128592 
Excluded because patient qualified in >1 exposure category 
0 
61981 
0 
128592 
Excluded based on Inclusion criteria #1 - Age >= 45 
-1814 
60167 
-3865 
124727 
Excluded based on Inclusion criteria #2 - Female 
-4439 
55728 
-9140 
115587 
Excluded based on Inclusion criteria #3.1 - History of vertebral fracture (including from 
inception to 90 days) 
-48548 
7180 
-103348 
12239 
Excluded based on Inclusion criteria #3.2 - Vertebral fracture diagnosis excluded in the 90 
days before cohort entry 
-740 
6440 
-969 
11270 
Excluded based on Inclusion criteria #4 - Osteoporosis 
-3 
6437 
-18 
11252 
Excluded based on Exclusion criteria #1 - Pregnancy 
-1 
6436 
-1 
11251 
Excluded based on Exclusion criteria #2 - Paget’s Disease 
-5 
6431 
-9 
11242 
Excluded based on Exclusion criteria #3.1 - Renal Osteodystrophy 
-2 
6429 
-1 
11241 
Excluded based on Exclusion criteria #3.2 - Osteomalacia 
-11 
6418 
-12 
11229 
Excluded based on Exclusion criteria #3.3 - Cushing syndrome and other disorders of adrenal 
glands 
-35 
6383 
-62 
11167 
Excluded based on Exclusion criteria #3.4 - Hyperparathyroidism and hypoparathyroidism 
-60 
6323 
-86 
11081 
Excluded based on Exclusion criteria #3.5 - Intestinal malabsorption 
-27 
6296 
-41 
11040 
Excluded based on Exclusion criteria #4 - Hypercalcemia and Hypocalcemia 
-14 
6282 
-23 
11017 
Excluded based on Exclusion criteria #5 - Malignant neoplasm, excluding non-melanoma 
skin cancer 
-500 
5782 
-936 
10081 
Excluded based on Exclusion criteria #6 - End-stage liver disease (ESLD) 
-31 
5751 
-51 
10030 
Excluded based on Exclusion criteria #7 – End-stage renal disease (ESRD) 
-6 
5745 
-14 
10016 
Excluded based on Exclusion criteria #8 - Nephrolithiasis or urolithiasis 
-52 
5693 
-109 
9907 
Excluded based on Exclusion criteria #9 - Kyphoplasty or vertebroplasty 
-17 
5676 
-47 
9860 

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Excluded based on Exclusion criteria #10 - Osteonecrosis of the jaw 
0 
5676 
-2 
9858 
Excluded based on Exclusion criteria #11 - Atypical subtrochanteric or diaphyseal femoral 
fractures 
-28 
5648 
-55 
9803 
Excluded based on Exclusion criteria #12 - Upper gastrointestinal disorders 
-170 
5478 
-221 
9582 
Excluded based on Exclusion criteria #13 - CCI (180 days) 
-2 
5476 
-1 
9581 
Excluded based on Exclusion criteria #14 - Drug addiction or alcohol abuse or not compliant 
-91 
5385 
-58 
9523 
Excluded based on Exclusion criteria #15 - Oral bisphosphonate use 
-499 
4886 
-1024 
8499 
Excluded based on Exclusion criteria #16 - SERMs, Calcitonin, HRT 
-101 
4785 
-321 
8178 
Excluded based on Exclusion criteria #17 - Zoledronic acid use 
-2 
4783 
-7 
8171 
Excluded based on Exclusion criteria #18 - Intravenous ibandronate or pamidronate 
-1 
4782 
-1 
8170 
Excluded based on Exclusion criteria #19 - Denosumab use 
-10 
4772 
-4 
8166 
Excluded based on Exclusion criteria #20 - PTH or PTH analogue use 
-44 
4728 
-137 
8029 
Excluded based on Exclusion criteria #21 - Romosozumab 
0 
4728 
0 
8029 
Final cohort 
  
4728 
  
8029 
 
 
6. Variables  
 
6.1 Exposure-related variables:  
 
Study drug:  
New initiation of injectable subcutaneous teriparatide (20 μg daily). New initiation is defined as no use of teriparatide in the prior 730 
days before treatment initiation (washout period). New users of teriparatide are not allowed to receive risedronate within the 180 days 
prior to treatment initiation. 
 
Comparator agent: 
New initiation of oral risedronate (35 mg weekly). New initiation is defined as no use of risedronate in the prior 180 days before 
treatment initiation (washout period). New users of risedronate are not allowed to receive teriparatide within the 730 days prior to 
treatment initiation. 
 
6.2 Preliminary Covariates: 
• Age 
• Combined Comorbidity Index (CCI), measured over the baseline covariate assessment period, defined as 180 days prior to and 

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including index date. 
 
Covariates listed above represent only a small subset of covariates that will ultimately be controlled for in the design and analysis. 
We use the covariates above only for initial feasibility analyses to judge whether there is likely to be sufficient overlap between 
treatment groups to proceed with the study. Remaining covariates are defined only after the study has passed the initial feasibility 
analysis and the initial power assessment and are listed in Table 1 (Appendix B). Gender is not included since the study is already 
restricted to female subjects. 
 
6.3 Outcome variables and study follow-up:  
 
6.3.1 Outcome variables 
 
Effectiveness outcome variables of interest (definitions provided in Appendix A): 
§ Primary outcome: Vertebral fracture (algorithm adapted from Wright et al. 2019) 
§ Secondary outcome: Non-vertebral fracture 
 
6.3.2 Study follow-up 
As-treat (AT) analysis will be conducted with treatment defined as the index drug on the day of cohort entry. Similar to the trial, the 
patients will be followed for 24 months. A grace period and a risk exposure window of 60 days will be considered in the primary 
analysis. 
The follow-up will start the day after drug initiation (i.e., cohort entry date), as described in the VERO trial, and will continue until the 
earliest date of the following events: 
§ The first occurrence of the outcome of interest, 
§ The date of end of continuous registration in the database, 
§ Discontinuation of the index drugs, 
§ Addition of the index drug from the other group or crossover, 
§ End of the study period, 
§ Measured death event occurs, 
§ Nursing home admission 

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o Nursing home admissions are considered a censoring event because the data sources utilized typically provide little to 
no data on a patient, particularly on drug utilization, after admission. We will utilize this as an exclusion reason for 
cohorts for the same reason. 
 
A subgroup analysis will be performed by age categorized by tertiles () emulating one of the prespecified subgroup analyses of the 
VERO trial (Geusens P et al. 2018). 
 
7. Initial Feasibility Analysis  
Aetion report name: 
For teriparatide vs. risedronate 
Optum CDM - https://bwh-dope.aetion.com/projects/details/1640/results/66361/result/0 
IBM® MarketScan®- https://bwh-dope.aetion.com/projects/details/1641/results/66364/result/0 
 
Date conducted: 02/25/2021 
 
Complete Aetion feasibility analysis using age and CCI as the only covariates and the primary endpoint (Section 6.3.1) as the 
outcome. No measures of association will be computed nor will incidence rates stratified by treatment group. 
 
• Report patient characteristics by treatment group 
• Report summary parameters of study population FEASIBILITY- FOR STUDY OUTCOME 
• Report reasons for censoring in the overall study population 
• Report overall risk of the primary outcome. 
 
8. Initial Power Assessment 
 
Aetion report name: 
For teriparatide vs. risedronate 
Optum CDM - https://bwh-dope.aetion.com/projects/details/1640/results/66362/result/0 
IBM® MarketScan®- https://bwh-dope.aetion.com/projects/details/1641/results/66363/result/0 
 
Date conducted:  02/25/2021 
 

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In order to complete the initial power analysis, the dummy outcome of a 90-day gap in database enrollment will be used. This outcome 
is used to ensure that no information on the comparative risks of the outcomes of interest are available at this stage. Complete a 1:1 
PS-matched comparative analysis using this outcome. PS should include only 2 covariates: age and combined comorbidity index. 
Power calculations are based on the formulas from Chow et al. (2008). 
 
• Stop analyses until feasibility and power are reviewed by primary investigators and FDA. Reviewers evaluate the results of the 
analyses described above in Sections 7 and 8, including numbers of patients, patient characteristics, follow-up time, and reasons 
for censoring by treatment group, as well as overall rates of outcomes and study power. These parameters are re-evaluated and 
reported in the subsequent sections, after incorporating feedback and refining the protocol. 
 
• Stop analyses until feasibility and power are reviewed by primary investigators, FDA, and assigned members of advisory board. 
 
 
Reviewed by PI: 
Shirley Wang 
Jessica Franklin 
Date reviewed: 
03/17/2021 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
03/16/2021 
Reasons for stopping 
analysis (if required): 
 
 
 
9. Balance Assessment 
For teriparatide vs. risedronate 
Optum CDM: https://bwh-dope.aetion.com/projects/details/1640/rwrs/67726 
IBM® MarketScan®: https://bwh-dope.aetion.com/projects/details/1641/rwrs/67727 
 
 
Date conducted: 03/29/21 
 
After review of initial feasibility and power analyses, complete creation of the remaining covariates from Section 6.2. Again, using the 
dummy outcome of a 90-day gap in database enrollment, complete a 1:1 PS-matched analysis. The PS should include the complete list 
of covariates. 
 
• Provide plot of PS distributions stratified by treatment group. 

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Note- Please refer to Appendix B.  
 
 
• Report covariate balance after matching. 
 
Note- For Table 1, please refer to Appendix B.  
 
 
• Report reasons for censoring by treatment group. 
 
 
Overall 
Referent 
Exposure 
Dummy outcome 
0 (0%) 
0 (0%) 
0 (0%) 
Death 
28 (0.65%) 
9 (0.21%) 
19 (0.44%) 
End of patient enrollment 
715 (16.5%) 
300 (6.92%) 
415 (9.58%) 
End of index exposure 
157 (3.62%) 
70 (1.62%) 
87 (2.01%) 
Maximum follow-up time 
442 (10.20%) 
185 (4.27%)  
257 (5.93%) 
End of index exposure 
2775 (64.03%) 
1522 (35.12%) 
1253 (28.91%) 
Start of an additional exposure 
37 (0.85%) 
9 (0.21%) 
28 (0.65%) 
Nursing Home 
180 (4.15%) 
72 (1.66%) 
108 (2.49%) 
 
• Report follow-up time by treatment group. 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum CDM 
IBM® MarketScan® 
Overall Patient Population 
163.5 [88 - 415] 
190 [100 - 431.5] 
Referent - Risedronate 
148 [88 - 371] 
148 [88 - 331] 
Exposure - Teriparatide 
192 [88 - 446] 
234 [113 - 533] 
 
• Report overall risk of the primary outcome. 

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Optum CDM 
IBM® MarketScan® 
Pooled 
Risk per 1,000 patients 
15.9 
18.9 
17.8 
 
 
10. Final Power Assessment 
 
Date conducted:  
 
• Re-calculate power in the appropriate excel table, using the revised number of matched patients from the PS-match in Section 9. 
All other parameters in the table should be the same as in Section 8. 
o Pooled 
 
 
o Optum CDM 
Superiority Analysis
Number of patients matched
4,334
Reference
2,167
Exposed
2,167
Risk per 1,000 patients
17.80
Desired HR from RCT
0.44
Alpha (2-sided)
0.05
Number of events expected
77.1452
Power
0.950063363

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o IBM® MarketScan® 
 
 
Superiority Analysis
Number of patients matched
1,494
Reference
747
Exposed
747
Risk per 1,000 patients
15.90
Desired HR from RCT
0.44
Alpha (2-sided)
0.05
Number of events expected
23.7546
Power
0.516274582
Superiority Analysis
Number of patients matched
2,840
Reference
1,420
Exposed
1,420
Risk per 1,000 patients
18.90
Desired HR from RCT
0.44
Alpha (2-sided)
0.05
Number of events expected
53.676
Power
0.852553869

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
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•
Stop analyses until balance and final power assessment are reviewed by primary investigators, FDA, and assigned members of
advisory board.
Reviewed by PI: 
Shirley Wang 
Date reviewed: 
04/16/2021 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
04/15/2021 
Reasons for stopping 
analysis (if required): 
11. Study Confidence and Concerns
Deadline for voting on study confidence and listing concerns: 
Date votes and concerns are summarized:    
•
If final feasibility and power analyses are reviewed and approved, proceed to the remaining protocol steps.
•
All study team and advisory board members that review this protocol should at this stage provide their level of confidence for the
success of the RWD study in the Google Form. This form also provides space for reviewers to list any concerns that they feel may
contribute to a failure to replicate the findings of the RCT, including differences in study populations, poor measurement of study
variables, or residual confounding. All responses will be kept confidential and individual-level results will only be shared with the
individual respondent.
•
After the deadline for voting has passed, provide the distribution of responses and summarize all concerns here.
12. Register study protocol on clinicalTrials.gov
Date conducted:   
•
Register the study on clinicalTrials.gov and upload this document.
13. Comparative Analyses
Aetion report name: 
Date conducted:    
13.1 
For primary analysis: 
04/30/2021

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
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13.2 
For sensitivity analyses: 
14. Requested Results
14.1 
Table 1: Baseline characteristics before and after adjustment 
Variable 
Before adjustment 
After adjustment 
Referent 
Exposure 
Std. diff. 
Referent 
Exposure 
Std. diff. 
Number of patients 
- 
- 
Age categories 
… 
14.2 
Table 2: Follow-up time 
Patient Group 
Median Follow-Up Time (Days) [IQR] 
Overall Patient Population 
Referent 
Exposure 
14.3 
Table 3: Censoring events 
Overall 
Referent 
Exposure 

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Outcome 
Death 
Start of an additional exposure 
End of index exposure 
Specified date reached 
End of patient data 
End of patient enrollment 
… 
14.4 
Table 4: Results from primary analyses; 
Analysis 
No. exposed events 
No. referent events 
Exposed rate 
Referent rate 
HR (95% CI) 
Crude 
Analysis 1 
Analysis 2 
... 
HR, Hazard Ratio; CI, Confidence Interval. 
14.5 
Table 5: Results from secondary analyses. 

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15. References
Kendler DL, Marin F, Zerbini CAF, Russo LA, Greenspan SL, Zikan V, Bagur A, Malouf-Sierra J, Lakatos P, Fahrleitner-Pammer A, 
Lespessailles E, Minisola S, Body JJ, Geusens P, Möricke R, López-Romero P. Effects of teriparatide and risedronate on new fractures 
in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled 
trial. Lancet. 2018 Jan 20;391(10117):230-240. doi: 10.1016/S0140-6736(17)32137-2.  
Wright NC, Daigle SG, Melton ME, Delzell ES, Balasubramanian A, Curtis JR. The Design and Validation of a New Algorithm to 
Identify Incident Fractures in Administrative Claims Data. J Bone Miner Res. 2019 Oct;34(10):1798-1807. doi: 10.1002/jbmr.3807. 
Geusens P, Marin F, Kendler DL, Russo LA, Zerbini CA, Minisola S, Body JJ, Lespessailles E, Greenspan SL, Bagur A, Stepan JJ, 
Lakatos P, Casado E, Moericke R, López-Romero P, Fahrleitner-Pammer A. Effects of Teriparatide Compared with Risedronate on the 
Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial. J Bone Miner Res. 2018 
May;33(5):783-794. doi: 10.1002/jbmr.3384. 
Chow S, Shao J, Wang H. 2008.  Sample Size Calculations in Clinical Research. 2nd Ed. Chapman & Hall/CRC Biostatistics 
Series. page 177. 

#
VERO trial definitions
Implementation in routine care
References/Rationale
Color coding
E
Exposure: 20 μg of teriparatide once daily
Exposure: new use of Teriparatide (washout 730 days)
NDC Generic Name: TERIPARATIDE
NDC codes: 00002897101, 54868540600, 00002840001, 47781065289
Brand names: FORTEO
CPT/HCPCS Procedure Code: J3110
Washout period - Criteria 20.1, 20.7
Criteria
C
Reference: 35 mg of oral risedronate once weekly
Aim: To compare the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis
Comparator: new-use of Risedronate (washout 180 days)
NDC Generic Name: RISEDRONATE SODIUM, RISEDRONATE SODIUM/CALCIUM CARBONATE
NDC codes: 00093309819, 00093309829, 00093309844, 00093309956, 00093310056, 00093550919, 00093550944, 
00093777113, 00093777119, 00093777179, 00149047001, 00149047101, 00149047103, 00149047201, 00149047204, 
00149047501, 00149047701, 00149047801, 00149047803, 00378404493, 00378411493, 00378415032, 00378415053, 
00378471499, 00430047015, 00430047115, 00430047203, 00430047207, 00430047801, 00430047802, 00430097903, 
00591204403, 00591204454, 00591207504, 00591207539, 00591210230, 00591210930, 00591387604, 16590072104, 
16714087002, 23490924500, 33342010707, 33342010807, 33342010937, 33342010950, 47335066862, 47335066868, 
47335092860, 47335092867, 49999044804, 54569546200, 54868438600, 54868467100, 54868551800, 54868606900, 
59762040504, 59762040505, 59762040601, 59762040603, 59762040704, 60505309702, 60505309704, 60505316500, 
63304044009, 63304044011, 65862051730, 65862051830, 65862051904, 65862051908, 65862087003, 65862087011, 
68115068104
Brand names: ACTONEL, ATELVIA
Adequate mapping in claims
Intermediate mapping in claims
New radiographic vertebral fractures during a 24-month study period.
[Lateral spine radiographs were repeated at 12 and 24 months or early termination for new vertebral fractures. 
Additional unscheduled radiographs were done at any interim visit to detect new clinical vertebral fractures if the 
patient reported back pain clinically suggestive of a vertebral fracture.]
Measured 1 day after drug initiation:
Vertebral Fractures:
Algorithm include the following case-qualifyng (CQ):
CQ = 1 Inpatient claim with primary diagnosis code 
ICD9 dx: 805.x, 806.x, 733.13
ICD10 dx: S12.0xxA,S12.0xxB-S12.6xxA, S12.6xxB, S12 S22.0xxA, S22.0xxB (excluding “traumatic” and “burst” fractures 
which are high-energy fractures), M48.50XA, M80.08XA (excluding “stress” and “fatigue” fractures which are fractures caused 
by abnormal stress on normal bones)
OR
CQ = 2 Non-inpatient claim with any diagnosis code [ICD9 dx: 805.x, 806.x, 733.13; ICD10 dx: S12.0xxA,S12.0xxB-S12.6xxA, 
S12.6xxB, S12 S22.0xxA, S22.0xxB (excluding “traumatic” and “burst” fractures), M48.50XA, M80.08XA (excluding “stress” 
and “fatigue” fractures)] AND procedure code HCPCS (22305, 22310, 22315, 22318, 22319, 22325-22328, 22510-22515, 
22520-22525, 27200, 27202, 72291, 72292, 76012, 76013, 77082, 77085, 77086, S2360-S2363)
OR
CQ = 3 Non-inpatient claim with diagnosis code [ICD9 dx: 805.x, 806.x, 733.13; ICD10 dx: S12.0xxA,S12.0xxB-S12.6xxA, 
S12.6xxB, S12 S22.0xxA, S22.0xxB (excluding “traumatic” and “burst” fractures), M48.50XA, M80.08XA (excluding “stress” 
and “fatigue” fractures)] AND Physician E&M codes (HCPCS: 99024, 99058,99201-99215, 99241-99245, 99271-99285, 
99301–99355, 99366, 99385–99387,99395–99404, 99429, 99499) AND, up to 10 days earlier (or on the same day), 
Outpatient claim of spine imaging codes (HCPCS: 72010-72159, 72240-72285, 72295) []
Wright NC, Daigle SG, Melton ME, Delzell ES, 
Balasubramanian A, Curtis JR. The Design and Validation 
of a New Algorithm to Identify Incident Fractures in 
Administrative Claims Data. J Bone Miner Res. 2019 
Oct;34(10):1798-1807. doi: 10.1002/jbmr.3807. Epub 
2019 Aug 5. PMID: 31170317.
Poor mapping or cannot be measured in claims 
Can't be measured in claims but not important for the analysis
1
Postmenopausal women ≥ 45 years of age at the time of entry into the trial, whose last menstrual period occurred at 
least 2 years prior to entry into the trial, and are sufficiently mobile to complete study visits.
Female, ≥ 45 years of age at the time of drug initiation
2
Women < 55 years of age in whom a bilateral oophorectomy cannot clearly be documented must have their 
postmenopausal status confirmed by a serum FSH level > 40 IU/L and serum estradiol level < 20 pg/mL or < 73 pmol/L.
Measured 180 days prior to and including day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position):
Excluded if patients had pregnancy codes Pregnancy (see "Pregnancy codes")
INCLUSION CRITERIA
Please see the following Google Drive for further details or any missing information: 
https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV?usp=sharing
ICD-10 codes are not listed in this document because of excel cell size limitations and excessive number of ICD-10 codes. Full ICD-10 code 
lists will be available in the above Google Drive Folder (link above). ICD-9 to ICD-10 code conversions were completed using a SAS 
macro that implements forward/ backward mapping based on the CMS ICD-9 to ICD-10 mapping:
 https://www.nber.org/data/icd9-icd-10-cm-and-pcs-crosswalk-general-equivalence-mapping.html
Trial details - clinicaltrial.gov NCT01709110
EXPOSURE vs. COMPARISON
PRIMARY OUTCOME
Appendix A

2
A minimum of 2 moderate (SQ2) or 1 severe (SQ3) vertebral fragility fractures
[radiographic evidence of at least two moderate (ie, a reduction in vertebral body height of 26–40%) or one severe 
(more than 40% reduction) prevalent vertebral fragility fracture]
Measured from enorlment to 90 days prior to the day of drug initiation in inpatient or outpatient care setting (any position):
Vertebral Fractures diagnosis:
ICD9 diagnosis codes: 805.x, 806.x, 733.13
ICD10 diagnosis codes: M48.4, M48.5, M80.x, S12.x, S22.x, S32.x
Vertebral fracture procedures:
HCPCS codes: 22305, 22310, 22315, 22318, 22319, 22325-22328, 22510-22515, 22520-22525, 27200, 27202, 72291, 
72292, 76012, 76013, 77082, 77085, 77086, S2360-S2363
ICD10 px: 0PQ3xx, 0PQ4xx, 0PR3xx, 0PR4xx, 0PS3xx, 0PS4xx
ICD-9 px: 03.53
NB. We excluded patients with diagnosis of vertebral 
fractures from 89 days prior to and including the day of 
drug initiation to increase the probability of measuring 
incident vertebral fractures and not prevalent vertebral 
fractures. The 90-day gap is described in: Wright NC, 
Daigle SG, Melton ME, Delzell ES, Balasubramanian A, 
Curtis JR. The Design and Validation of a New Algorithm 
to Identify Incident Fractures in Administrative Claims 
Data. J Bone Miner Res. 2019 Oct;34(10):1798-1807. 
doi: 10.1002/jbmr.3807. 
3
AP lumbar spine or total hip or femoral neck BMD ≥ 1.5 SD below the average BMD for young healthy, non-Hispanic, 
Caucasian women (T-score ≤ –1.5 SD).
Measured start of all available data and including day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
Osteoporosis diagnosis
ICD-9 diagnosis: 733.00, 733.01, 733.02, 733.03, 733.09, 733.13
ICD-10 diagnosis: M81.0, M81.6, M81.8, M80.88*, M80.00*, M80.01*, M80.02*, M80.03*, M80.04*, M80.05*, M80.06*, 
M80.07*, M80.08*
OR
Osteoporosis treatments:
Alendronate, Ibandronate, Risedronate, Etidronate, Tiludronate, Denosumab, Calcitonin, Romosozumab, Raloxifene, ZA, 
Pamidronate (reported as osteoporosis drug in the VERO trial) 
4
Without language barrier, cooperative, able to come to the clinic for all follow-up visits; has given informed consent 
before entering the study and after being informed of the medications and procedures to be used in this study.
N/A
5
In the opinion of the investigator, is willing to be trained and to use the pen injector daily, is able to satisfactorily use a 
pen-type injection delivery system, or is willing to receive daily subcutaneous injections from a caregiver who has been 
trained to use the pen injector.
N/A
1.1
Increased baseline risk of osteosarcoma. This includes patients with Paget’s disease of the bone [..]. As elevation of 
serum alkaline phosphatase activity may indicate the presence of Paget’s disease, an unexplained elevation of this 
enzyme activity will also be exclusionary.
Measured 365 days prior to and including the day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
ICD-9 diagnosis: 731.0 Osteitis deformans without mention of bone tumor (Paget's Disease)
ICD-10 diagnosis: M88.xxx Osteitis deformans [Paget's disease of bone]
+  Tiludronate (exclusion criteria 21.1)
1.2
[...] previous primary skeletal malignancy, or skeletal exposure to therapeutic irradiation.
Captured in criteria 13
2
History of unresolved skeletal diseases that affect bone metabolism, other than osteoporosis, including renal 
osteodystrophy, osteomalacia, hyperparathyroidism (uncorrected), hypoparathyroidism, and intestinal 
malabsorption.
Measured 365 days prior to and including the day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position):
Renal osteodystrophy
ICD-9 diagnosis: 588.0 
ICD-10 diagnosis: N25.0 
Osteomalacia
ICD-9 diagnosis: 268.2 
ICD-10 diagnosis: M83.x 
Cushing syndrome and disorders of adrenal glands:
ICD-9 diagnosis: 255.xx
ICD-10 diagnosis: E24.x
Hyperparathyroidism and hypoparathyroidism:
ICD-9 diagnosis: 252.x, 588.81 
ICD-10 diagnosis: E21.x, E20.x, N25.81
Intestinal Malabsorption:
Celiac disease, Tropical sprue, Pancreatic steatorrhea, Non-celiac gluten sensitivity, Malabsorption due to intolerance 
elsewhere classified, Whipple's disease, Other intestinal malabsorption:
ICD-9 diagnosis: 579.xx, 040.2
ICD-10 diagnosis: K90.xx
3
Abnormally elevated values of serum albumin-corrected calcium levels at baseline, defined as ≥ 10.6 mg/dL (or ≥ 2.65 
mmol/L). In cases with borderline non-eligible values (≥ 10.6 and ≤ 10.7 mg/dL), a re-test would be allowed during the 
screening period.
Measured 30 days prior to and including the day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
Hypercalcemia and Hypocalcemia:
ICD-9 diagnosis: 275.41, 275.42
ICD-10 diagnosis: E83.51, E83.52
4
Abnormally low values of serum albumin- corrected calcium levels at baseline, defined as < 8.0 mg/dL (or < 2.0 mmol/L). 
In cases with borderline non-eligible values (> 7.8 to < 8.0 mg/dL), a re-test would be allowed during the screening 
period to allow normalization with vitamin D and calcium supplements before the randomization visit.
see Criteria 3
EXCLUSION CRITERIA
Appendix A

5
Abnormally elevated values of serum intact PTH(1-84) at baseline defined as > 72 pg/mL (or > 7.6 pmol/L). In cases with 
borderline non-eligible values (> 72 and < 79 pg/mL), a re-test would be allowed during the screening period to allow 
normalization with vitamin D and calcium supplements before the randomization visit.
see Criteria 2, 3 and 6
6
Severe vitamin D deficiency at baseline defined as 25-hydroxy-vitamin D levels < 9.2 ng/mL (or < 23 nmol/L). In cases 
with borderline non-eligible values (> 8.0 and < 9.2 ng/mL), a re-test would be allowed during the screening period to 
allow normalization with vitamin D supplement before the randomization visit.
N/A
7
Abnormal thyroid function not corrected by therapy. Patients with subclinical hyperthyroidism or hypothyroidism, 
defined as abnormally low or high TSH values respectively, with normal fT4 values are eligible to participate in the 
study.
N/A
8
History of malignant neoplasms in the 5 years prior to Visit 2, with the exception of superficial basal cell or squamous 
cell carcinomas of the skin that have been definitively treated. Patients with carcinoma in situ of the uterine cervix 
treated definitively more than 1 year prior to entry into the study may be randomized. Patients with multiple myeloma 
or metastases to bone are excluded.
Measured 1825 days (5 years) prior to and including the day of drug initiation in inpatient or outpatient care setting (any 
diagnosis position): 
Malignant neoplasm:
ICD-9 diagnosis: 140.xx-208.xx (except 173.xx, non-melanoma skin cancer)
ICD-10 diagnosis: C00-C43, C45-C97, D45
9
Active liver disease or clinical jaundice. Significantly impaired hepatic function, defined as aspartate aminotransferase 
(AST) > 75 U/L or alanine aminotransferase (ALT) > 75 U/L or gamma-glutamyl transpeptidase (GGT) > 300 U/L.
Measured 365 days prior to and including the day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
Cirrhosis: 
ICD-9 Diagnosis: 571.2, 571.5, 571.6
ICD-10 Diagnosis: K70.11, K70.2, K70.3x, K70.4x, K74.x
Hepatic decompensation: 
ICD-9 Diagnosis: 456.0, 456.20, 456.1, 456.21, 789.5, 789.59, 572.2, 567.0, 567.2, 567.21, 567.22, 567.29, 567.8, 567.89, 
567.9, 572.4 
ICD-10 Diagnosis: R18.x, I85.x, K72.x, K65.x, K66.x, K67
HCC is already excluded with exclusion criteria 13
10
Significantly impaired renal function as defined by a calculated endogenous creatinine clearance (ClCr) < 30 mL/min 
using the following Cockcroft-Gault formula for ClCr (Cockcroft and Gold 1976)
Measured 365 days prior to and including the day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
Chronic kidney disease stages IV-V, ESRD
2 codes for occurrence of ESRD/dialysis (either inpatient or outpatient), separated by at least 30 days:
ICD-9 Diagnosis: 585.6, V45.1, V56.0, V56.8, 585.5
ICD-9 Procedure: 39.95, 54.98 
ICD-10 Diagnosis:  N18.5, N18.6, Z49.31, Z49.32, Z99.2
ICD-10 Procedure: 3E1M39Z, 5A1D60Z, 5A1D00Z, 3E1M39Z, 5A1D60Z, 5A1D00Z
HCPCS/CPT codes: 50360, 50380, 90921, 90925, 90935, 90937, 90940, 90947, 90957, 90959, 90960, 90961, 90962, 
90966, 90969, 90989, 99512, G0257, G0318, G0319, G0322, G0326, S9335, S9339, 50365, 90920, 90924, 90945, 90958, 
90965, 90970, 90993, 90999, 99559, G0314, G0315, G0316, G0317, G0323, G0327
OR
Kidney transplant:
ICD-9 Diagnosis: 996.81, V42.0
ICD-9 Procedure: 55.6, 55.69
ICD-10 Diagnosis: T86.10, T86.13, T86.19, Z48.22, Z94.0, T86.11, T86.12
ICD-10 Procedure: 0TY00Z0, 0TY00Z2, 0TY10Z0, 0TY00Z1, 0TY10Z1, 0TY10Z2
HCPCS/CPT Code: 50360, 50365
11
History of nephrolithiasis or urolithiasis within 1 year prior to Visit 2.
Measured 365 days prior to and including the day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
ICD-9 Diagnosis: 592.xx, 274.11
ICD-10 Diagnosis: N20.xx-N23.xx
ICD-9 Px: 57.0, 59.95, 56.0, 98.19, 98.51
ICD-10 Px: 0TCB7ZZ, 0TCB8ZZ, 0TFB0ZZ, 0TFB3ZZ, 0TFB4ZZ, 0TFB7ZZ, 0TFB8ZZ, 0TFC0ZZ, 0TFC3ZZ, 0TFC4ZZ, 0TFC7ZZ, 0TFC8ZZ, 
0T9B7ZZ, 0T9B8ZZ, 0T9C7ZZ, 0T9C8ZZ, 0TCC7ZZ, 0TCC8ZZ, 0TC37ZZ, 0TC38ZZ, 0TC47ZZ, 0TC48ZZ, 0TC67ZZ, 0TC68ZZ, 
0TC77ZZ, 0TC78ZZ, 0TC68ZZ, 0TC77ZZ, 0TC78ZZ, 0T768DZ, 0T778DZ, 0T788DZ, 0TF38ZZ, 0TF48ZZ, 0TF68ZZ, 0TF78ZZ
CPT: 52005, 52310, 52332, 52352, 52353, 52356, 52317, 52318
12
Considered imminent candidates for kyphoplasty or vertebroplasty before Visit 2.
N/A
13
Patients who have been treated with kyphoplasty or vertebroplasty at 3 or more levels before Visit 2, regardless of the 
time since the last procedure.
see Criteria 14
14
Patients who have been treated with kyphoplasty or vertebroplasty within the last 6 months before Visit 2.
Measured 180 days prior to and including the day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
ICD-9 Procedure: 
Kyphoplasty: 81.66
Vertebroplasty: 81.65
ICD-10 Procedure: 
Kyphoplasty 0PS33ZZ, OPU33JZ, OPS43ZZ, OPU43JZ, OQS03ZZ, OQU03JZ, 0QS13ZZ, QS13JZ0, 0QSS3ZZ, 0QUS3JZ 
Vertebroplasty 0PU33JZ, 0PU34JZ, 0PU43JZ, 0PU44JZ, 0QU03JZ, 0QU04JZ, 0QU13JZ, 0QU14JZ
CPT: 22514, 22515, 22520, 22521, 22522, 22523, 22524, 22525, 0200T, C9718, C9719, S2362, S2363
Appendix A

15
Patients with history of osteonecrosis of the jaw or who are, according to the clinical judgment of the investigator, at 
high risk to develop osteonecrosis of the jaw, including poor oral hygiene, scheduled invasive dental procedures, high 
doses of bisphosphonates and/or chemotherapy to treat malignancy.
Measured start of all available data and including day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
History of osteonecrosis of the jaw:
ICD-9 diagnosis: 733.45
ICD-10 diagnosis: M87.180
16
Patients with history of atypical subtrochanteric or diaphyseal femoral fractures, according to the diagnostic criteria of 
the American Society for Bone and Mineral Research Task Force (Shane et al. 2010).
Measured start of all available data and including day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
ICD-9 diagnosis: 733.15, 821.0x, 821.1x
ICD-10 diagnosis: M84.75, S72.3x
17
Active or recent history of significant upper gastrointestinal disorders, such as esophageal disorders which delay 
esophageal transit or emptying (e.g. stricture or achalasia).
Measured 365 days prior to and including day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
ICD-9 diagnosis: 530.x
ICD-10 diagnosis: K22.x
18
Unable to stand or sit in the upright position for at least 30 minutes.
N/A
19
Poor medical or psychiatric condition for participating in a clinical study, in the opinion of the investigator.
Measured on the day of drug initiation:
CCI >=10  (life expectancy less than the expected duration of the trial)
20
History of excessive consumption of alcohol or abuse of drugs in the 1 year prior to Visit 2, in the opinion of the 
investigator.
Measured 365 days prior to and including day of drug initiation in inpatient or outpatient care setting (any diagnosis 
position): 
Alcohol Abuse or Dependence
ICD-9 diagnosis: 291.xx, 303.xx, 305.0x, 571.0x, 571.1x, 571.2x, 571.3x, 357.5x, 425.5x, E860.0x (CMS has not released 
mapping for new ICD10 for this code), V11.3x
ICD-10 diagnosis: F10.x, K70.x, G62.1, I42.6, 099.31x
OR
Drug Abuse or Dependence 
ICD-9 diagnosis: 292.xx, 304.xx, 305.2x-305.9x, 648.3x
ICD-10 diagnosis: F11.x, F12.x, F13.x, F14.x, F15.x, F16.x, F17.2x, F18.x, F19.x, F55.2, G62.0, 099.32x
OR
Non-compliance: 
ICD-9 diagnosis: V45.12, V15.81 
ICD-10 diagnosis: Z91.19, Z91.15 
Patorno, Elisabetta et al. "Cardiovascular outcomes 
associated with canagliflozin versus other non-gliflozin 
antidiabetic drugs: population based cohort study." 
BMJ 2018;360:k119 
http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of 
Heart Failure Hospitalization in Routine Clinical Care: A 
First Analysis from the Empagliflozin Comparative 
Effectiveness and Safety (EMPRISE) Study."  Circulation. 
2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
21.1
Previous treatment with the following bone active drugs is allowed but treatment must be discontinued at Visit 1 or at 
the time indicated below: 
1. Oral bisphosphonates (including alendronate, risedronate, ibandronate, etidronate).
Measured 180 days prior to and 1 day before the day of drug initiation:
Generic names:
Alendronate, Ibandronate, Risedronate, Etidronate, Tiludronate
21.2
2. SERMs, calcitonin, estrogen (oral, transdermal, or injectable), progestin, estrogen analog, estrogen agonist, estrogen
antagonist or tibolone, androgens, strontium ranelate, or active vitamin D3 analogues.
Measured 30 days prior to and 1 day before the day of drug initiation:
Generic names: 
SERMs: OSPEMIFENE, RALOXIFENE HCL, ESTROGENS, CONJUGATED/BAZEDOXIFENE ACETATE
Calcitonin
HRT: estrogens, progestins, androgens
Strontium not approved in USA for treatment of 
osteoporosis.
Vitamin D3 analogues over the counter
21.3
Intravenous zoledronate, if the last dose was administered at least 12 months before Visit 1.
Measured  365 days prior to and 1 day before the day of drug initiation:
Generic name:
Zoledronic Acid
21.4
Intravenous ibandronate or pamidronate, if the last dose was administered at least 3 months before Visit 1.
Measured  90 days prior to and 1 day before the day of drug initiation:
Generic name:
 ibandronate or pamidronate
CPT codes:
C9229, J1740, C9411, J2430
21.5
Subcutaneous denosumab, if the last dose was administered at least 6 months before Visit 1.
Measured  180 days prior to and 1 day before the day of drug initiation:
Generic name:
Denosumab
21.6
Fluoride unless given at therapeutic doses (> 20 mg/day) for more than 3 months in the 2 years prior to Visit 1, or for 
more than a total of 2 years, or at any dosages within the 6 months prior to Visit 2 (previous or current use of 
fluoridated water or topical dental fluoride treatment is permitted).
N/A
Sodium Fluoride is not used to treat the osteoporosiss 
since 2001/2002 when a RCT and sub meta-analysis 
showed an increased of risk of fractures in the exp arm
21.7
Prior treatment with PTH, teriparatide, or other PTH analogs; or prior participation in any other clinical trial studying 
PTH, teriparatide, or other PTH analogs.
Measured 730 days (2 years) prior to and 1 day before the day of drug initiation:
Generic names:
parathyroid hormone , teriparatide, abaloparatide
Brand names:
Natpara® (parathyroid hormone) Forteo® Bonsity (teriparatide) Tymlos® (abaloparatide)
22
Known hypersensitivity to teriparatide or risedronate, or to any diluents or excipients of teriparatide or risedronate 35 
mg/week oral tablet.
N/A
Appendix A

23
Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product 
or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to 
be scientifically or medically compatible with this study.
N/A
24
Site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a 
spouse, parent, child, or sibling, whether biological or legally adopted.
N/A
25
Lilly employees or employees of third-party organizations (TPOs) involved in study who require exclusion of their 
employees.
N/A
26
Romosozumab
Measured 180 days prior to and 1 day before the day of drug initiation:
Generic name:
Romosozumab
Appendix A

Pregnancy 
Dx codes 
650   NORMAL DELIVERY
660   OBSTRUCTED LABOR
661   ABNORMALITY OF FORCES OF LABOR
662   LONG LABOR
663   UMBILICAL CORD COMPLICATIONS DURING LABOR AND DELIVERY
664   TRAUMA TO PERINEUM AND VULVA DURING DELIVERY
665   OTHER OBSTETRICAL TRAUMA
667   RETAINED PLACENTA OR MEMBRANES WITHOUT HEMORRHAGE
668   COMPLICATIONS OF THE ADMINISTRATION OF ANESTHETIC OR OTHER SEDATION IN LABOR AND DELIVERY
669.94   UNSPECIFIED COMPLICATION OF LABOR AND DELIVERY POSTPARTUM CONDITION OR COMPLICATION
V24   POSTPARTUM CARE AND EXAMINATION
V24.0   POSTPARTUM CARE AND EXAMINATION IMMEDIATELY AFTER DELIVERY
V24.1   POSTPARTUM CARE AND EXAMINATION OF LACTATING MOTHER
V24.2   ROUTINE POSTPARTUM FOLLOW
V27   OUTCOME OF DELIVERY
V27.0   MOTHER WITH SINGLE LIVEBORN
V27.1   MOTHER WITH SINGLE STILLBORN
V27.2   MOTHER WITH TWINS BOTH LIVEBORN
V27.3   MOTHER WITH TWINS ONE LIVEBORN AND ONE STILLBORN
V27.4   MOTHER WITH TWINS BOTH STILLBORN
V27.5   MOTHER WITH OTHER MULTIPLE BIRTH ALL LIVEBORN
V27.6   MOTHER WITH OTHER MULTIPLE BIRTH SOME LIVEBORN
V27.7   MOTHER WITH OTHER MULTIPLE BIRTH ALL STILLBORN
V27.9   MOTHER WITH UNSPECIFIED OUTCOME OF DELIVERY
Procedure codes 
72.0   LOW FORCEPS OPERATION
72.1   LOW FORCEPS OPERATION WITH EPISIOTOMY
72.2   MID FORCEPS OPERATION
72.21   MID FORCEPS OPERATION WITH EPISIOTOMY
72.29   OTHER MID FORCEPS OPERATION
72.3   HIGH FORCEPS OPERATION
72.31   HIGH FORCEPS OPERATION WITH EPISIOTOMY
72.39   OTHER HIGH FORCEPS OPERATION
72.4   FORCEPS ROTATION OF FETAL HEAD
72.5   BREECH EXTRACTION
72.51   PARTIAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.52   OTHER PARTIAL BREECH EXTRACTION
72.53 TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
Appendix A

72.53   TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.54   OTHER TOTAL BREECH EXTRACTION
72.6   FORCEPS APPLICATION TO AFTERCOMING HEAD
72.7   VACUUM EXTRACTION
72.71   VACUUM EXTRACTION WITH EPISIOTOMY
72.79   OTHER VACUUM EXTRACTION
72.8   OTHER SPECIFIED INSTRUMENTAL DELIVERY
72.9   UNSPECIFIED INSTRUMENTAL DELIVERY
73.0   ARTIFICIAL RUPTURE OF MEMBRANES
73.01   INDUCTION OF LABOR BY ARTIFICIAL RUPTURE OF MEMBRANES
73.09   OTHER ARTIFICIAL RUPTURE OF MEMBRANES
73.1   OTHER SURGICAL INDUCTION OF LABOR
73.2   INTERNAL AND COMBINED VERSION AND EXTRACTION
73.21   INTERNAL AND COMBINED VERSION WITHOUT EXTRACTION
73.22   INTERNAL AND COMBINED VERSION WITH EXTRACTION
73.3   FAILED FORCEPS
73.4   MEDICAL INDUCTION OF LABOR
73.5   MANUALLY ASSISTED DELIVERY
73.51   MANUAL ROTATION OF FETAL HEAD
73.59   OTHER MANUALLY ASSISTED DELIVERY
73.6   EPISIOTOMY
73.8   OPERATIONS ON FETUS TO FACILITATE DELIVERY
73.9   OTHER OPERATIONS ASSISTING DELIVERY
73.91   EXTERNAL VERSION ASSISTING DELIVERY
73.92   REPLACEMENT OF PROLAPSED UMBILICAL CORD
73.93   INCISION OF CERVIX TO ASSIST DELIVERY
73.94   PUBIOTOMY TO ASSIST DELIVERY
73.99   OTHER OPERATIONS ASSISTING DELIVERY
74.0   CLASSICAL CESAREAN SECTION
74.1   LOW CERVICAL CESAREAN SECTION
74.2   EXTRAPERITONEAL CESAREAN SECTION
74.3   REMOVAL OF EXTRATUBAL ECTOPIC PREGNANCY
74.4   CESAREAN SECTION OF OTHER SPECIFIED TYPE
74.9   CESAREAN SECTION OF UNSPECIFIED TYPE
74.91   HYSTEROTOMY TO TERMINATE PREGNANCY
74.99   OTHER CESAREAN SECTION OF UNSPECIFIED TYPE
75.4   MANUAL REMOVAL OF RETAINED PLACENTA
75.5   REPAIR OF CURRENT OBSTETRIC LACERATION OF UTERUS
75.6   REPAIR OF OTHER CURRENT OBSTETRIC LACERATION
75.7   MANUAL EXPLORATION OF UTERINE CAVITY, POSTPARTUM
75.9   OTHER OBSTETRIC OPERATIONS
Appendix A

AFTER PS MATCHING
Optum
MarketScan
BEFORE PS MATCHING
The c-statistics for the propensity score model, pre-matching was 0.781. 
The post-matching c-statistic was 0.578.
The c-statistics for the propensity score model, pre-matching was 0.758. 
The post-matching c-statistic was 0.554.
Appendix B

Variable
Risedronate
Teriparatide
St. Diff.
Risedronate
Teriparatide
St. Diff.
Risedronate
Teriparatide
St. Diff.
Number of patients
3,875
853
6,464
1,565
10,339 
2,418 
Demographic characteristics
6,812 
5,344 
6,691 
13,208 
13,503 
18,552 
Age
...mean (sd)
72.33 (10.26)
71.04 (10.08)
0.127
70.65 (12.30)
70.66 (11.23)
-0.001
71.28 (11.58)
70.79 (10.84)
0.044
...median [IQR]
74.00 [65.00, 81.00]
72.00 [63.00, 79.50]
0.197
71.00 [60.00, 81.00]
71.00 [62.00, 80.00]
0.000
72.12 (11.58)
71.35 (10.84)
0.069
Age categories
...< 50; n (%)
46 (1.2%)
12 (1.4%)
-0.018
138 (2.1%)
24 (1.5%)
0.045
184 (1.8%)
036 (1.5%)
0.024
...50 - 64; n (%)
906 (23.4%)
250 (29.3%)
-0.134
2,387 (36.9%)
526 (33.6%)
0.069
3,293 (31.9%)
776 (32.1%)
-0.004
...65 - 79; n (%)
1,787 (46.1%)
378 (44.3%)
0.036
2,013 (31.1%)
616 (39.4%)
-0.174
3,800 (36.8%)
994 (41.1%)
-0.088
...>= 80; n (%)
1,136 (29.3%)
213 (25.0%)
0.097
1,926 (29.8%)
399 (25.5%)
0.096
3,062 (29.6%)
612 (25.3%)
0.096
Region
...Northeast; n (%)
352 (9.1%)
78 (9.1%)
0.000
1,422 (22.0%)
260 (16.6%)
0.137
1,774 (17.2%)
338 (14.0%)
0.088
...Midwest; n (%)
580 (15.0%)
149 (17.5%)
-0.068
1,712 (26.5%)
475 (30.4%)
-0.087
2,292 (22.2%)
624 (25.8%)
-0.084
...South; n (%)
1,522 (39.3%)
350 (41.0%)
-0.035
2,085 (32.3%)
593 (37.9%)
-0.118
3,607 (34.9%)
943 (39.0%)
-0.085
...West; n (%)
1,421 (36.7%)
276 (32.4%)
0.091
1,245 (19.3%)
237 (15.1%)
0.111
2,666 (25.8%)
513 (21.2%)
0.109
Calendar Time year of initiation
...Jan 2004 - Dec 2006; n (%)
288 (7.4%)
44 (5.2%)
0.091
1,402 (21.7%)
150 (9.6%)
0.338
1,690 (16.3%)
194 (8.0%)
0.256
...Jan 2007 - Dec 2009; n (%)
1,164 (30.0%)
126 (14.8%)
0.371
1,880 (29.1%)
301 (19.2%)
0.233
3,044 (29.4%)
427 (17.7%)
0.278
...Jan 2010 - Dec 2012; n (%)
1,142 (29.5%)
157 (18.4%)
0.262
1,629 (25.2%)
416 (26.6%)
-0.032
2,771 (26.8%)
573 (23.7%)
0.071
...Jan 2013 - Dec 2015; n (%)
658 (17.0%)
232 (27.2%)
-0.248
1,014 (15.7%)
416 (26.6%)
-0.269
1,672 (16.2%)
648 (26.8%)
-0.260
...Jan 2016 - Mar 2020; n (%) #
623 (16.1%)
294 (34.5%)
-0.433
539 (8.3%)
282 (18.0%)
-0.027
1,162 (11.2%)
576 (23.8%)
-0.336
Race
...White; n (%)
2,764 (71.3%)
640 (75.0%)
-0.084
NA
NA
NA
2,764 (71.3%)
640 (75.0%)
-0.084
...Black or African American; n (%)
216 (5.6%)
44 (5.2%)
0.018
NA
NA
NA
216 (5.6%)
44 (5.2%)
0.018
...Asian; n (%)
185 (4.8%)
31 (3.6%)
0.060
NA
NA
NA
185 (4.8%)
31 (3.6%)
0.060
...Others; n (%)
710 (18.3%)
138 (16.2%)
0.056
NA
NA
NA
710 (18.3%)
138 (16.2%)
0.056
Metropolitan Statistical Area
...Urban; n (%)
NA
NA
NA
4,979 (77.0%)
1,173 (75.0%)
0.047
4,979 (77.0%)
1,173 (75.0%)
0.047
...Rural; n (%)
NA
NA
NA
37 (0.6%)
41 (2.6%)
-0.160
37 (0.6%)
41 (2.6%)
-0.160
...Unknown/Missing; n (%)
NA
NA
NA
1,448 (22.4%)
351 (22.4%)
0.000
1,448 (22.4%)
351 (22.4%)
0.000
General Health Related Measures
Smoking; n (%)
355 (9.2%)
123 (14.4%)
-0.162
290 (4.5%)
108 (6.9%)
-0.104
645 (6.2%)
231 (9.6%)
-0.126
Obesity or Overweight; n (%)
259 (6.7%)
85 (10.0%)
-0.120
222 (3.4%)
88 (5.6%)
-0.106
481 (4.7%)
173 (7.2%)
-0.106
   Obesity; n (%)
175 (4.5%)
57 (6.7%)
-0.096
174 (2.7%)
64 (4.1%)
-0.077
349 (3.4%)
121 (5.0%)
-0.080
   Overweight; n (%)
97 (2.5%)
33 (3.9%)
-0.080
58 (0.9%)
28 (1.8%)
-0.078
155 (1.5%)
061 (2.5%)
-0.071
Cardiovascular Measures
Hypertension; n (%)
2,391 (61.7%)
503 (59.0%)
0.055
2,945 (45.6%)
744 (47.5%)
-0.038
5,336 (51.6%)
1,247 (51.6%)
0.000
Hyperlipidemia; n (%)
2,236 (57.7%)
439 (51.5%)
0.125
2,462 (38.1%)
620 (39.6%)
-0.031
4,698 (45.4%)
1,059 (43.8%)
0.032
Coronary artery disease (MI, angina, Coronary atherosclerosis and other forms of 
chronic ischemic heart disease); n (%)
669 (17.3%)
126 (14.8%)
0.068
897 (13.9%)
262 (16.7%)
-0.078
1,566 (15.1%)
388 (16.0%)
-0.025
    Old MI; n (%)
103 (2.7%)
21 (2.5%)
0.013
62 (1.0%)
20 (1.3%)
-0.028
165 (1.6%)
041 (1.7%)
-0.008
    Acute MI; n (%)
48 (1.2%)
6 (0.7%)
0.052
65 (1.0%)
18 (1.2%)
-0.019
113 (1.1%)
024 (1.0%)
0.010
    ACS/unstable angina; n (%)
63 (1.6%)
10 (1.2%)
0.034
90 (1.4%)
25 (1.6%)
-0.016
153 (1.5%)
035 (1.4%)
0.008
    Stable angina; n (%)
119 (3.1%)
18 (2.1%)
0.063
145 (2.2%)
37 (2.4%)
-0.013
264 (2.6%)
055 (2.3%)
0.019
    Coronary atherosclerosis and other CHD; n (%)
576 (14.9%)
107 (12.5%)
0.070
800 (12.4%)
232 (14.8%)
-0.070
1,376 (13.3%)
339 (14.0%)
-0.020
    History of CABG or PTCA; n (%)
104 (2.7%)
19 (2.2%)
0.032
57 (0.9%)
24 (1.5%)
-0.055
161 (1.6%)
043 (1.8%)
-0.015
Cerebrovascular disease (Stroke, TIA, Late effects); n (%)
290 (7.5%)
61 (7.2%)
0.011
415 (6.4%)
94 (6.0%)
0.017
705 (6.8%)
155 (6.4%)
0.016
   Stroke (Ischemic or hemorrhagic); n (%)
160 (4.1%)
39 (4.6%)
-0.025
260 (4.0%)
54 (3.5%)
0.026
420 (4.1%)
093 (3.8%)
0.015
   TIA; n (%)
126 (3.3%)
20 (2.3%)
0.061
187 (2.9%)
47 (3.0%)
-0.006
313 (3.0%)
067 (2.8%)
0.012
   Late effects of cerebrovascular disease; n (%)
95 (2.5%)
27 (3.2%)
-0.042
92 (1.4%)
20 (1.3%)
0.009
187 (1.8%)
047 (1.9%)
-0.007
Heart Failure; n (%)
279 (7.2%)
44 (5.2%)
0.083
466 (7.2%)
128 (8.2%)
-0.038
745 (7.2%)
172 (7.1%)
0.004
Peripheral Vascular Disease (PVD) or PVD Surgery; n (%)
310 (8.0%)
73 (8.6%)
-0.022
393 (6.1%)
102 (6.5%)
-0.016
703 (6.8%)
175 (7.2%)
-0.016
Atrial fibrillation and Other cardiac dysrhythmia; n (%)
593 (15.3%)
154 (18.1%)
-0.075
906 (14.0%)
259 (16.5%)
-0.070
1,499 (14.5%)
413 (17.1%)
-0.071
   Atrial fibrillation; n (%)
323 (8.3%)
81 (9.5%)
-0.042
492 (7.6%)
153 (9.8%)
-0.078
815 (7.9%)
234 (9.7%)
-0.064
   Other cardiac dysrhythmia; n (%)
416 (10.7%)
121 (14.2%)
-0.106
602 (9.3%)
175 (11.2%)
-0.063
1,018 (9.8%)
296 (12.2%)
-0.077
Diabetes Related Measures
Diabetes with or w/o complications; n (%)
763 (19.7%)
175 (20.5%)
-0.020
1,010 (15.6%)
277 (17.7%)
-0.056
1,773 (17.1%)
452 (18.7%)
-0.042
   Diabetes mellitus without mention of complications; n (%)
689 (17.8%)
151 (17.7%)
0.003
891 (13.8%)
236 (15.1%)
-0.037
1,580 (15.3%)
387 (16.0%)
-0.019
   Diabetes with specified complications; n (%)
248 (6.4%)
61 (7.2%)
-0.032
292 (4.5%)
101 (6.5%)
-0.088
540 (5.2%)
162 (6.7%)
-0.063
   Diabetes with unspecified complications; n (%)
34 (0.9%)
6 (0.7%)
0.022
41 (0.6%)
14 (0.9%)
-0.035
075 (0.7%)
020 (0.8%)
-0.012
Hypoglycemia; n (%)
54 (1.4%)
17 (2.0%)
-0.046
56 (0.9%)
24 (1.5%)
-0.055
110 (1.1%)
041 (1.7%)
-0.051
GI Conditions
Upper GI (Diseases of esophagus, stomach and duodenum); n (%)
852 (22.0%)
254 (29.8%)
-0.179
861 (13.3%)
334 (21.3%)
-0.213
1,713 (16.6%)
588 (24.3%)
-0.192
GI bleeding; n (%)
167 (4.3%)
30 (3.5%)
0.041
269 (4.2%)
54 (3.5%)
0.036
436 (4.2%)
084 (3.5%)
0.036
Marketscan
POOLED
Unmatched
Optum
Appendix B

Eating disorders, Non-infective enteritis and colitis, postoperative disorders of the 
digestive system; n (%)
616 (15.9%)
165 (19.3%)
-0.089
794 (12.3%)
238 (15.2%)
-0.084
1,410 (13.6%)
403 (16.7%)
-0.087
   Eating disorders (Anorexia and Bulimia); n (%)
238 (6.1%)
68 (8.0%)
-0.074
190 (2.9%)
74 (4.7%)
-0.094
428 (4.1%)
142 (5.9%)
-0.083
Non-infective enteritis and colitis; n (%)
323 (8.3%)
85 (10.0%)
-0.059
469 (7.3%)
143 (9.1%)
-0.066
792 (7.7%)
228 (9.4%)
-0.061
   Intraoperative and postprocedural complications and disorders of    digestive system; 
n (%)
158 (4.1%)
38 (4.5%)
-0.020
257 (4.0%)
55 (3.5%)
0.026
415 (4.0%)
093 (3.8%)
0.010
Disorders of gallbladder, biliary tract and pancreas; n (%)
100 (2.6%)
40 (4.7%)
-0.112
188 (2.9%)
57 (3.6%)
-0.039
288 (2.8%)
097 (4.0%)
-0.066
Rheumatic Conditions
Rheumatoid arthritis and other inflammatory polyarthropathies; n (%)
317 (8.2%)
116 (13.6%)
-0.174
426 (6.6%)
184 (11.8%)
-0.181
743 (7.2%)
300 (12.4%)
-0.176
Osteoarthrosis; n (%)
1,276 (32.9%)
347 (40.7%)
-0.162
1,580 (24.4%)
528 (33.7%)
-0.206
2,856 (27.6%)
875 (36.2%)
-0.185
Other rheumatic disorders (including gout); n (%)
2,635 (68.0%)
630 (73.9%)
-0.130
4,107 (63.5%)
1,129 (72.1%)
-0.185
6,742 (65.2%)
1,759 (72.7%)
-0.163
    Gout and other crystal arthropathies; n (%)
80 (2.1%)
15 (1.8%)
0.022
68 (1.1%)
29 (1.9%)
-0.066
148 (1.4%)
044 (1.8%)
-0.032
    Other rheumatic disorders; n (%)
2,620 (67.6%)
628 (73.6%)
-0.132
4,090 (63.3%)
1,123 (71.8%)
-0.182
6,710 (64.9%)
1,751 (72.4%)
-0.162
Neuro Conditions
Parkinson's disease; n (%)
10 (0.3%)
1 (0.1%)
0.045
8 (0.1%)
2 (0.1%)
0.000
018 (0.2%)
003 (0.1%)
0.026
Alzheimer and other Dementia Disease ; n (%)
373 (9.6%)
62 (7.3%)
0.083
462 (7.1%)
100 (6.4%)
0.028
835 (8.1%)
162 (6.7%)
0.054
Seizure disorders (epilepsy); n (%)
61 (1.6%)
21 (2.5%)
-0.064
73 (1.1%)
31 (2.0%)
-0.073
134 (1.3%)
052 (2.2%)
-0.069
Delirium/Psychosis; n (%)
148 (3.8%)
33 (3.9%)
-0.005
192 (3.0%)
62 (4.0%)
-0.054
340 (3.3%)
095 (3.9%)
-0.032
Other Conditions
Vitamin D deficiency; n (%)
633 (16.3%)
250 (29.3%)
-0.314
546 (8.4%)
263 (16.8%)
-0.255
1,179 (11.4%)
513 (21.2%)
-0.268
Liver disease; n (%)
128 (3.3%)
37 (4.3%)
-0.052
194 (3.0%)
56 (3.6%)
-0.034
322 (3.1%)
093 (3.8%)
-0.038
Chronic kidney disease stages I-III; n (%)
414 (10.7%)
81 (9.5%)
0.040
181 (2.8%)
72 (4.6%)
-0.095
595 (5.8%)
153 (6.3%)
-0.021
Chronic kidney disease stages IV-V, ESRD; n (%)
130 (3.4%)
18 (2.1%)
0.080
60 (0.9%)
27 (1.7%)
-0.071
190 (1.8%)
045 (1.9%)
-0.007
Premature menopause; n (%)
5 (0.1%)
3 (0.4%)
-0.060
9 (0.1%)
1 (0.1%)
0.000
014 (0.1%)
004 (0.2%)
-0.026
Oophorectomy; n (%)
5 (0.1%)
0 (0.0%)
0.045
1 (0.0%)
1 (0.1%)
-0.045
006 (0.1%)
001 (0.0%)
0.045
COPD; n (%)
623 (16.1%)
142 (16.6%)
-0.014
798 (12.3%)
244 (15.6%)
-0.095
1,421 (13.7%)
386 (16.0%)
-0.065
Asthma; n (%)
384 (9.9%)
102 (12.0%)
-0.067
484 (7.5%)
147 (9.4%)
-0.068
868 (8.4%)
249 (10.3%)
-0.065
Obstructive sleep apnea; n (%)
151 (3.9%)
60 (7.0%)
-0.137
143 (2.2%)
62 (4.0%)
-0.104
294 (2.8%)
122 (5.0%)
-0.114
Syncope; n (%)
215 (5.5%)
49 (5.7%)
-0.009
343 (5.3%)
89 (5.7%)
-0.018
558 (5.4%)
138 (5.7%)
-0.013
Falls; n (%)
499 (12.9%)
180 (21.1%)
-0.220
173 (2.7%)
128 (8.2%)
-0.244
672 (6.5%)
308 (12.7%)
-0.212
VTE; n (%)
142 (3.7%)
36 (4.2%)
-0.026
203 (3.1%)
58 (3.7%)
-0.033
345 (3.3%)
094 (3.9%)
-0.032
Gait abnormality; n (%)
498 (12.9%)
179 (21.0%)
-0.217
578 (8.9%)
202 (12.9%)
-0.129
1,076 (10.4%)
381 (15.8%)
-0.161
Osteopenia; n (%)
1,260 (32.5%)
279 (32.7%)
-0.004
1,720 (26.6%)
344 (22.0%)
0.107
2,980 (28.8%)
623 (25.8%)
0.067
History of hip and femur fractures; n (%)
162 (4.2%)
66 (7.7%)
-0.148
280 (4.3%)
141 (9.0%)
-0.189
442 (4.3%)
207 (8.6%)
-0.176
Other Fractures ; n (%)
267 (6.9%)
123 (14.4%)
-0.245
425 (6.6%)
199 (12.7%)
-0.208
692 (6.7%)
322 (13.3%)
-0.221
Glucocorticoid-Induced Osteoporosis; n (%)
4 (0.1%)
3 (0.4%)
-0.060
1 (0.0%)
2 (0.1%)
-0.045
005 (0.0%)
005 (0.2%)
-0.063
Combined comorbidity score
...mean (sd)
1.03 (2.10)
1.28 (2.22)
-0.116
0.66 (1.57)
0.92 (1.78)
-0.155
0.80 (1.79)
1.05 (1.95)
-0.134
...median [IQR]
0.00 [0.00, 2.00]
1.00 [0.00, 2.00]
-0.463
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.000
0.00 (1.79)
0.35 (1.95)
-0.187
Frailty Score: Empirical Version 365 days as Categories
...< 0.12908; n (%)
1,600 (41.3%)
372 (43.6%)
-0.047
2,630 (40.7%)
507 (32.4%)
0.173
4,230 (40.9%)
879 (36.4%)
0.093
...0.12908 - 0.1631167; n (%)
852 (22.0%)
173 (20.3%)
0.042
1,510 (23.4%)
342 (21.9%)
0.036
2,362 (22.8%)
515 (21.3%)
0.036
...>= 0.1631167; n (%)
1,423 (36.7%)
308 (36.1%)
0.012
2,324 (36.0%)
716 (45.8%)
-0.200
3,747 (36.2%)
1,024 (42.3%)
-0.125
Medication Use
Use of oral corticosteroids; n (%)
1,089 (28.1%)
314 (36.8%)
-0.187
1,859 (28.8%)
572 (36.5%)
-0.165
2,948 (28.5%)
886 (36.6%)
-0.174
Use of antidepressants; n (%)
1,247 (32.2%)
327 (38.3%)
-0.128
2,143 (33.2%)
654 (41.8%)
-0.178
3,390 (32.8%)
981 (40.6%)
-0.162
Use of anticonvulsants; n (%)
565 (14.6%)
180 (21.1%)
-0.170
904 (14.0%)
376 (24.0%)
-0.257
1,469 (14.2%)
556 (23.0%)
-0.228
Use of beta blocker OR calcium channel blocker; n (%)
1,270 (32.8%)
270 (31.7%)
0.024
2,060 (31.9%)
537 (34.3%)
-0.051
3,330 (32.2%)
807 (33.4%)
-0.026
Use of PPIs; n (%)
965 (24.9%)
254 (29.8%)
-0.110
1,761 (27.2%)
569 (36.4%)
-0.199
2,726 (26.4%)
823 (34.0%)
-0.166
Use of opioids; n (%)
1,674 (43.2%)
488 (57.2%)
-0.283
2,972 (46.0%)
976 (62.4%)
-0.334
4,646 (44.9%)
1,464 (60.5%)
-0.316
Use of antipsychotics; n (%)
108 (2.8%)
28 (3.3%)
-0.029
230 (3.6%)
61 (3.9%)
-0.016
338 (3.3%)
089 (3.7%)
-0.022
Use of anxiolytics/hypnotics; n (%)
435 (11.2%)
91 (10.7%)
0.016
816 (12.6%)
255 (16.3%)
-0.105
1,251 (12.1%)
346 (14.3%)
-0.065
Use of dementia meds; n (%)
219 (5.7%)
34 (4.0%)
0.079
349 (5.4%)
77 (4.9%)
0.023
568 (5.5%)
111 (4.6%)
0.041
Use of antiparkinsonian meds; n (%)
127 (3.3%)
33 (3.9%)
-0.032
226 (3.5%)
67 (4.3%)
-0.041
353 (3.4%)
100 (4.1%)
-0.037
Use of Benzodiazepine; n (%)
568 (14.7%)
200 (23.4%)
-0.223
1,491 (23.1%)
433 (27.7%)
-0.106
2,059 (19.9%)
633 (26.2%)
-0.150
All antidiabetic medications; n (%)
439 (11.3%)
82 (9.6%)
0.056
670 (10.4%)
188 (12.0%)
-0.051
1,109 (10.7%)
270 (11.2%)
-0.016
ACEI/ARB; n (%)
1,555 (40.1%)
280 (32.8%)
0.152
2,234 (34.6%)
527 (33.7%)
0.019
3,789 (36.6%)
807 (33.4%)
0.067
Use of Anticoagulants; n (%)
301 (7.8%)
81 (9.5%)
-0.061
548 (8.5%)
176 (11.2%)
-0.091
849 (8.2%)
257 (10.6%)
-0.082
Use of Amiodarone; n (%)
36 (0.9%)
10 (1.2%)
-0.029
81 (1.3%)
26 (1.7%)
-0.033
117 (1.1%)
036 (1.5%)
-0.035
Digoxin; n (%)
92 (2.4%)
17 (2.0%)
0.027
233 (3.6%)
45 (2.9%)
0.039
325 (3.1%)
062 (2.6%)
0.030
Use of Diuretics; n (%)
1,273 (32.9%)
251 (29.4%)
0.076
2,096 (32.4%)
515 (32.9%)
-0.011
3,369 (32.6%)
766 (31.7%)
0.019
Use of Aspirin; n (%)
24 (0.6%)
6 (0.7%)
-0.012
90 (1.4%)
25 (1.6%)
-0.016
114 (1.1%)
031 (1.3%)
-0.018
NSAIDs (NOT including aspirin); n (%)
807 (20.8%)
218 (25.6%)
-0.114
1,496 (23.1%)
365 (23.3%)
-0.005
2,303 (22.3%)
583 (24.1%)
-0.043
HRT (Use of estrogens, progestins, androgens); n (%)
240 (6.2%)
50 (5.9%)
0.013
445 (6.9%)
102 (6.5%)
0.016
685 (6.6%)
152 (6.3%)
0.012
Other Pressors; n (%)
24 (0.6%)
5 (0.6%)
0.000
38 (0.6%)
24 (1.5%)
-0.088
062 (0.6%)
029 (1.2%)
-0.064
Use of Statins ; n (%)
1,599 (41.3%)
276 (32.4%)
0.185
2,393 (37.0%)
568 (36.3%)
0.015
3,992 (38.6%)
844 (34.9%)
0.077
Selective Estrogen Receptor Modulators (SERMs); n (%)
61 (1.6%)
19 (2.2%)
-0.044
128 (2.0%)
39 (2.5%)
-0.034
189 (1.8%)
058 (2.4%)
-0.042
Appendix B

Healthcare Utilization Measures
Use of any drugs claims
...mean (sd)
21.89 (16.94)
25.76 (18.99)
-0.215
20.60 (16.91)
26.58 (19.21)
-0.330
21.08 (16.92)
26.29 (19.13)
-0.289
Number of office visits
...mean (sd)
8.64 (6.54)
12.05 (7.91)
-0.470
9.37 (7.10)
12.43 (8.14)
-0.401
9.10 (6.90)
12.30 (8.06)
-0.427
Number of ED visits
...mean (sd)
0.59 (1.17)
0.77 (1.14)
-0.156
0.49 (1.14)
0.65 (1.25)
-0.134
0.53 (1.15)
0.69 (1.21)
-0.136
Number of Hospitalizations
...mean (sd)
0.32 (0.86)
0.48 (1.01)
-0.171
1.83 (6.41)
2.30 (5.88)
-0.076
1.26 (5.10)
1.66 (4.77)
-0.081
Recent hospitalization (-30 days to Index Rx date); n (%)
55 (1.4%)
21 (2.5%)
-0.080
125 (1.9%)
37 (2.4%)
-0.034
180 (1.7%)
058 (2.4%)
-0.049
Old hospitalizations (-450 to -31 days); n (%)
579 (14.9%)
200 (23.4%)
-0.217
1,301 (20.1%)
420 (26.8%)
-0.159
1,880 (18.2%)
620 (25.6%)
-0.180
Number of Endocrinologist visits
...mean (sd)
0.14 (0.67)
0.52 (1.28)
-0.372
1.52 (2.62)
1.77 (2.97)
-0.089
1.00 (2.11)
1.33 (2.51)
-0.142
Number of DXA test performed
...mean (sd)
0.57 (0.57)
0.74 (0.56)
-0.301
0.41 (0.51)
0.50 (0.53)
-0.173
0.47 (0.53)
0.58 (0.54)
-0.206
Number of hospital days
...mean (sd)
3.68 (14.88)
5.21 (17.30)
-0.095
1.83 (6.41)
2.30 (5.88)
-0.076
2.52 (10.42)
3.33 (11.31)
-0.074
Occurrence of basic or comprehensive blood chemistry test; n (%)
2,611 (67.4%)
660 (77.4%)
-0.012
2,508 (38.8%)
720 (46.0%)
-0.146
5,119 (49.5%)
1,380 (57.1%)
-0.153
Number of HbA1C test ordered
...mean (sd)
0.55 (1.14)
0.53 (1.13)
0.018
0.28 (0.84)
0.27 (0.79)
0.012
0.38 (0.96)
0.36 (0.92)
0.021
Flexible Sigmoidoscopy or colonoscopy or CT virtual colonoscopy; n (%)
305 (7.9%)
77 (9.0%)
-0.040
649 (10.0%)
146 (9.3%)
0.024
954 (9.2%)
223 (9.2%)
0.000
Number of Mammograms (Breast cancer screening); n (%)
1,955 (50.5%)
408 (47.8%)
0.054
3,028 (46.8%)
583 (37.3%)
0.193
4,983 (48.2%)
991 (41.0%)
0.145
Number of Pap smear (Cervical cancer screening); n (%)
873 (22.5%)
153 (17.9%)
0.115
1,683 (26.0%)
279 (17.8%)
0.199
2,556 (24.7%)
432 (17.9%)
0.167
Flu vaccine; n (%)
1,331 (34.3%)
318 (37.3%)
-0.063
1,329 (20.6%)
349 (22.3%)
-0.041
2,660 (25.7%)
667 (27.6%)
-0.043
Pneumococcal vaccine; n (%)
493 (12.7%)
168 (19.7%)
-0.191
417 (6.5%)
155 (9.9%)
-0.124
910 (8.8%)
323 (13.4%)
-0.147
Copay for pharmacy cost (charges in U.S. $)
...mean (sd)
32.47 (33.44)
39.58 (80.44)
-0.115
24.71 (28.10)
21.31 (23.34)
0.132
27.62 (30.21)
27.76 (51.33)
-0.003
...median [IQR]
24.33 [13.75, 40.90]
25.00 [12.09, 41.51]
-0.011
18.73 [8.26, 32.00]
16.84 [7.92, 28.17]
0.073
20.83 (30.21)
19.72 (51.33)
0.026
...Missing; n (%)
0 (0.0%)
1 (0.1%)
-0.018
0 (0.0%)
5 (0.3%)
-0.078
000 (0.0%)
006 (0.2%)
-0.063
Business Type
...Commercial; n (%)
1,313 (33.9%)
344 (40.3%)
-0.133
NA
NA
NA
1,313 (33.9%)
344 (40.3%)
-0.133
...Medicare; n (%)
2,562 (66.1%)
509 (59.7%)
0.133
NA
NA
NA
2,562 (66.1%)
509 (59.7%)
0.133
Insurance Plan Type
...Comprehensive; n (%)
NA
NA
NA
1,771 (27.4%)
476 (30.4%)
-0.066
1,771 (27.4%)
476 (30.4%)
-0.066
...HMO; n (%)
NA
NA
NA
922 (14.3%)
109 (7.0%)
0.238
922 (14.3%)
109 (7.0%)
0.238
...PPO; n (%)
NA
NA
NA
3,087 (47.8%)
780 (49.8%)
-0.040
3,087 (47.8%)
780 (49.8%)
-0.040
...Others; n (%)
NA
NA
NA
684 (10.6%)
200 (12.8%)
-0.068
684 (10.6%)
200 (12.8%)
-0.068
Aetion link to Optum results: https://bwh-dope.aetion.com/projects/details/1640/rwrs/67726
Aetion link to Marketscan results: https://bwh-dope.aetion.com/projects/details/1641/rwrs/67727
# The last cohort entry date in Optum is Mar 31, 2020 and in Marketscan is Dec 31, 2018
Appendix B

Variable
Risedronate
Teriparatide
St. Diff.
Risedronate
Teriparatide
St. Diff.
Risedronate
Teriparatide
St. Diff.
Number of patients
747
747
1,420
1,420
2,167 
2,167 
Demographic characteristics
Age
...mean (sd)
71.16 (10.45)
71.32 (10.12)
-0.016
70.57 (11.42)
70.82 (11.22)
-0.022
70.77 (11.10)
70.99 (10.85)
-0.020
...median [IQR]
73.00 [63.00, 79.00]
72.00 [63.00, 80.00]
0.097
71.00 [61.00, 79.00]
71.00 [62.00, 80.00]
0.000
71.69 (11.10)
71.34 (10.85)
0.032
Age categories*
...< 50; n (%)
8 (1.1%)
12 (1.6%)
-0.043
22 (1.5%)
23 (1.6%)
-0.008
030 (1.4%)
035 (1.6%)
-0.016
...50 - 64; n (%)
207 (27.7%)
208 (27.8%)
-0.002
478 (33.7%)
472 (33.2%)
0.011
685 (31.6%)
680 (31.4%)
0.004
...65 - 79; n (%)
350 (46.9%)
333 (44.6%)
0.046
571 (40.2%)
551 (38.8%)
0.029
921 (42.5%)
884 (40.8%)
0.034
...>= 80; n (%)
182 (24.4%)
194 (26.0%)
-0.037
349 (24.6%)
374 (26.3%)
-0.039
531 (24.5%)
568 (26.2%)
-0.039
Region*
...Northeast; n (%)
73 (9.8%)
69 (9.2%)
0.020
267 (18.8%)
250 (17.6%)
0.031
340 (15.7%)
319 (14.7%)
0.028
...Midwest; n (%)
117 (15.7%)
125 (16.7%)
-0.027
402 (28.3%)
419 (29.5%)
-0.026
519 (24.0%)
544 (25.1%)
-0.026
...South; n (%)
317 (42.4%)
302 (40.4%)
0.041
545 (38.4%)
530 (37.3%)
0.023
862 (39.8%)
832 (38.4%)
0.029
...West; n (%)
240 (32.1%)
251 (33.6%)
-0.032
206 (14.5%)
221 (15.6%)
-0.031
446 (20.6%)
472 (21.8%)
-0.029
Calendar Time year of initiation*
...Jan 2004 - Dec 2006; n (%)
44 (5.9%)
43 (5.8%)
0.004
150 (10.6%)
149 (10.5%)
0.003
194 (9.0%)
192 (8.9%)
0.004
...Jan 2007 - Dec 2009; n (%)
122 (16.3%)
123 (16.5%)
-0.005
297 (20.9%)
292 (20.6%)
0.007
419 (19.3%)
415 (19.2%)
0.003
...Jan 2010 - Dec 2012; n (%)
158 (21.2%)
153 (20.5%)
0.017
402 (28.3%)
397 (28.0%)
0.007
560 (25.8%)
550 (25.4%)
0.009
...Jan 2013 - Dec 2015; n (%)
190 (25.4%)
200 (26.8%)
-0.032
369 (26.0%)
361 (25.4%)
0.014
559 (25.8%)
561 (25.9%)
-0.002
...Jan 2016 - Mar 2020; n (%) #
233 (31.2%)
228 (30.5%)
0.015
202 (14.2%)
221 (15.6%)
-0.039
435 (20.1%)
449 (20.7%)
-0.015
Race*
...White; n (%)
562 (75.2%)
556 (74.4%)
0.018
NA
NA
NA
562 (75.2%)
556 (74.4%)
0.018
...Black or African American; n (%)
43 (5.8%)
40 (5.4%)
0.017
NA
NA
NA
43 (5.8%)
40 (5.4%)
0.017
...Asian; n (%)
29 (3.9%)
30 (4.0%)
-0.005
NA
NA
NA
29 (3.9%)
30 (4.0%)
-0.005
...Others; n (%)
113 (15.1%)
121 (16.2%)
-0.030
NA
NA
NA
113 (15.1%)
121 (16.2%)
-0.030
Metropolitan Statistical Area*
...Urban; n (%)
NA
NA
NA
1,089 (76.7%)
1,069 (75.3%)
0.033
1,089 (76.7%)
1,069 (75.3%)
0.033
...Rural; n (%)
NA
NA
NA
25 (1.8%)
28 (2.0%)
-0.015
25 (1.8%)
28 (2.0%)
-0.015
...Unknown/Missing; n (%)
NA
NA
NA
306 (21.5%)
323 (22.7%)
-0.029
306 (21.5%)
323 (22.7%)
-0.029
General Health Related Measures
Smoking; n (%)*
100 (13.4%)
93 (12.4%)
0.030
82 (5.8%)
91 (6.4%)
-0.025
182 (8.4%)
184 (8.5%)
-0.004
Obesity or Overweight; n (%)*
61 (8.2%)
68 (9.1%)
-0.032
68 (4.8%)
76 (5.4%)
-0.027
129 (6.0%)
144 (6.6%)
-0.025
   Obesity; n (%)
44 (5.9%)
45 (6.0%)
-0.004
51 (3.6%)
54 (3.8%)
-0.011
095 (4.4%)
099 (4.6%)
-0.010
   Overweight; n (%)
22 (2.9%)
27 (3.6%)
-0.039
22 (1.5%)
26 (1.8%)
-0.024
044 (2.0%)
053 (2.4%)
-0.027
Cardiovascular Measures
Hypertension; n (%)*
452 (60.5%)
446 (59.7%)
0.016
636 (44.8%)
663 (46.7%)
-0.038
1,088 (50.2%)
1,109 (51.2%)
-0.020
Hyperlipidemia; n (%)*
413 (55.3%)
403 (53.9%)
0.028
544 (38.3%)
551 (38.8%)
-0.010
957 (44.2%)
954 (44.0%)
0.004
Coronary artery disease (MI, angina, Coronary atherosclerosis and other forms of chronic 
ischemic heart disease); n (%)*
117 (15.7%)
111 (14.9%)
0.022
212 (14.9%)
222 (15.6%)
-0.019
329 (15.2%)
333 (15.4%)
-0.006
    Old MI; n (%)
14 (1.9%)
20 (2.7%)
-0.053
18 (1.3%)
17 (1.2%)
0.009
032 (1.5%)
037 (1.7%)
-0.016
    Acute MI; n (%)
7 (0.9%)
6 (0.8%)
0.011
16 (1.1%)
15 (1.1%)
0.000
023 (1.1%)
021 (1.0%)
0.010
    ACS/unstable angina; n (%)
12 (1.6%)
9 (1.2%)
0.034
16 (1.1%)
23 (1.6%)
-0.043
028 (1.3%)
032 (1.5%)
-0.017
    Stable angina; n (%)
24 (3.2%)
14 (1.9%)
0.083
33 (2.3%)
32 (2.3%)
0.000
057 (2.6%)
046 (2.1%)
0.033
    Coronary atherosclerosis and other CHD; n (%)
103 (13.8%)
94 (12.6%)
0.035
190 (13.4%)
195 (13.7%)
-0.009
293 (13.5%)
289 (13.3%)
0.006
    History of CABG or PTCA; n (%)
17 (2.3%)
16 (2.1%)
0.014
12 (0.8%)
18 (1.3%)
-0.049
029 (1.3%)
034 (1.6%)
-0.025
Cerebrovascular disease (Stroke, TIA, Late effects); n (%)*
39 (5.2%)
56 (7.5%)
-0.094
79 (5.6%)
88 (6.2%)
-0.025
118 (5.4%)
144 (6.6%)
-0.051
   Stroke (Ischemic or hemorrhagic); n (%)
23 (3.1%)
36 (4.8%)
-0.087
48 (3.4%)
50 (3.5%)
-0.005
071 (3.3%)
086 (4.0%)
-0.037
   TIA; n (%)
19 (2.5%)
18 (2.4%)
0.006
36 (2.5%)
45 (3.2%)
-0.042
055 (2.5%)
063 (2.9%)
-0.025
   Late effects of cerebrovascular disease; n (%)
12 (1.6%)
24 (3.2%)
-0.105
17 (1.2%)
19 (1.3%)
-0.009
029 (1.3%)
043 (2.0%)
-0.055
Heart Failure; n (%)*
36 (4.8%)
41 (5.5%)
-0.032
99 (7.0%)
115 (8.1%)
-0.042
135 (6.2%)
156 (7.2%)
-0.040
Peripheral Vascular Disease (PVD) or PVD Surgery; n (%)*
64 (8.6%)
62 (8.3%)
0.011
98 (6.9%)
88 (6.2%)
0.028
162 (7.5%)
150 (6.9%)
0.023
Atrial fibrillation and Other cardiac dysrhythmia; n (%)*
138 (18.5%)
132 (17.7%)
0.021
237 (16.7%)
226 (15.9%)
0.022
375 (17.3%)
358 (16.5%)
0.021
   Atrial fibrillation; n (%)
76 (10.2%)
70 (9.4%)
0.027
128 (9.0%)
131 (9.2%)
-0.007
204 (9.4%)
201 (9.3%)
0.003
   Other cardiac dysrhythmia; n (%)
111 (14.9%)
101 (13.5%)
0.040
164 (11.5%)
152 (10.7%)
0.025
275 (12.7%)
253 (11.7%)
0.031
Diabetes Related Measures
Diabetes with or w/o complications; n (%)*
161 (21.6%)
149 (19.9%)
0.042
255 (18.0%)
240 (16.9%)
0.029
416 (19.2%)
389 (18.0%)
0.031
   Diabetes mellitus without mention of complications; n (%)
143 (19.1%)
133 (17.8%)
0.034
220 (15.5%)
206 (14.5%)
0.028
363 (16.8%)
339 (15.6%)
0.033
   Diabetes with specified complications; n (%)
59 (7.9%)
48 (6.4%)
0.058
89 (6.3%)
86 (6.1%)
0.008
148 (6.8%)
134 (6.2%)
0.024
   Diabetes with unspecified complications; n (%)
7 (0.9%)
5 (0.7%)
0.022
11 (0.8%)
11 (0.8%)
0.000
018 (0.8%)
016 (0.7%)
0.012
PS-matched
Optum
Marketscan
POOLED
Appendix B

Hypoglycemia; n (%)*
9 (1.2%)
15 (2.0%)
-0.064
17 (1.2%)
22 (1.5%)
-0.026
026 (1.2%)
037 (1.7%)
-0.042
GI Conditions
Upper GI (Diseases of esophagus, stomach and duodenum); n (%)*
211 (28.2%)
217 (29.0%)
-0.018
269 (18.9%)
275 (19.4%)
-0.013
480 (22.2%)
492 (22.7%)
-0.012
GI bleeding; n (%)*
26 (3.5%)
27 (3.6%)
-0.005
58 (4.1%)
51 (3.6%)
0.026
084 (3.9%)
078 (3.6%)
0.016
Eating disorders, Non-infective enteritis and colitis, postoperative disorders of the 
digestive system; n (%)*
145 (19.4%)
146 (19.5%)
-0.003
206 (14.5%)
203 (14.3%)
0.006
351 (16.2%)
349 (16.1%)
0.003
   Eating disorders (Anorexia and Bulimia); n (%)
63 (8.4%)
60 (8.0%)
0.015
50 (3.5%)
62 (4.4%)
-0.046
113 (5.2%)
122 (5.6%)
-0.018
Non-infective enteritis and colitis; n (%)
69 (9.2%)
75 (10.0%)
-0.027
133 (9.4%)
124 (8.7%)
0.024
202 (9.3%)
199 (9.2%)
0.003
Intraoperative and postprocedural complications and disorders of digestive system; n 
(%)
34 (4.6%)
34 (4.6%)
0.000
58 (4.1%)
46 (3.2%)
0.048
092 (4.2%)
080 (3.7%)
0.026
Disorders of gallbladder, biliary tract and pancreas; n (%)*
33 (4.4%)
35 (4.7%)
-0.014
57 (4.0%)
52 (3.7%)
0.016
090 (4.2%)
087 (4.0%)
0.010
Rheumatic Conditions
Rheumatoid arthritis and other inflammatory polyarthropathies; n (%)*
95 (12.7%)
97 (13.0%)
-0.009
163 (11.5%)
150 (10.6%)
0.029
258 (11.9%)
247 (11.4%)
0.016
Osteoarthrosis; n (%)*
283 (37.9%)
298 (39.9%)
-0.041
445 (31.3%)
456 (32.1%)
-0.017
728 (33.6%)
754 (34.8%)
-0.025
Other rheumatic disorders (including gout); n (%)*
550 (73.6%)
548 (73.4%)
0.005
997 (70.2%)
1,005 (70.8%)
-0.013
1,547 (71.4%)
1,553 (71.7%)
-0.007
    Gout and other crystal arthropathies; n (%)
21 (2.8%)
15 (2.0%)
0.052
25 (1.8%)
25 (1.8%)
0.000
046 (2.1%)
040 (1.8%)
0.022
    Other rheumatic disorders; n (%)*
547 (73.2%)
546 (73.1%)
0.002
991 (69.8%)
1,000 (70.4%)
-0.013
1,538 (71.0%)
1,546 (71.3%)
-0.007
Neuro Conditions
Parkinson's disease; n (%)
1 (0.1%)
0 (0.0%)
0.045
3 (0.2%)
1 (0.1%)
0.026
004 (0.2%)
001 (0.0%)
0.063
Alzheimer and other Dementia Disease ; n (%)*
49 (6.6%)
56 (7.5%)
-0.035
71 (5.0%)
86 (6.1%)
-0.048
120 (5.5%)
142 (6.6%)
-0.046
Seizure disorders (epilepsy); n (%)
17 (2.3%)
13 (1.7%)
0.043
26 (1.8%)
27 (1.9%)
-0.007
043 (2.0%)
040 (1.8%)
0.015
Delirium/Psychosis; n (%)
30 (4.0%)
31 (4.1%)
-0.005
35 (2.5%)
57 (4.0%)
-0.085
065 (3.0%)
088 (4.1%)
-0.059
Other Conditions
Vitamin D deficiency; n (%)*
212 (28.4%)
206 (27.6%)
0.018
218 (15.4%)
217 (15.3%)
0.003
430 (19.8%)
423 (19.5%)
0.008
Liver disease; n (%)*
26 (3.5%)
33 (4.4%)
-0.046
49 (3.5%)
47 (3.3%)
0.011
075 (3.5%)
080 (3.7%)
-0.011
Chronic kidney disease stages I-III; n (%)*
70 (9.4%)
74 (9.9%)
-0.017
65 (4.6%)
59 (4.2%)
0.020
135 (6.2%)
133 (6.1%)
0.004
Chronic kidney disease stages IV-V, ESRD; n (%)
21 (2.8%)
17 (2.3%)
0.032
18 (1.3%)
21 (1.5%)
-0.017
039 (1.8%)
038 (1.8%)
0.000
Premature menopause; n (%)
1 (0.1%)
3 (0.4%)
-0.060
1 (0.1%)
1 (0.1%)
0.000
002 (0.1%)
004 (0.2%)
-0.026
Oophorectomy; n (%)
1 (0.1%)
0 (0.0%)
0.045
0 (0.0%)
1 (0.1%)
-0.045
001 (0.0%)
001 (0.0%)
0.000
COPD; n (%)*
123 (16.5%)
130 (17.4%)
-0.024
214 (15.1%)
207 (14.6%)
0.014
337 (15.6%)
337 (15.6%)
0.000
Asthma; n (%)*
80 (10.7%)
88 (11.8%)
-0.035
132 (9.3%)
135 (9.5%)
-0.007
212 (9.8%)
223 (10.3%)
-0.017
Obstructive sleep apnea; n (%)*
49 (6.6%)
48 (6.4%)
0.008
56 (3.9%)
50 (3.5%)
0.021
105 (4.8%)
098 (4.5%)
0.014
Syncope; n (%)*
39 (5.2%)
45 (6.0%)
-0.035
77 (5.4%)
85 (6.0%)
-0.026
116 (5.4%)
130 (6.0%)
-0.026
Falls; n (%)*
134 (17.9%)
142 (19.0%)
-0.028
79 (5.6%)
81 (5.7%)
-0.004
213 (9.8%)
223 (10.3%)
-0.017
VTE; n (%)
33 (4.4%)
32 (4.3%)
0.005
49 (3.5%)
47 (3.3%)
0.011
082 (3.8%)
079 (3.6%)
0.011
Gait abnormality; n (%)*
141 (18.9%)
140 (18.7%)
0.005
167 (11.8%)
166 (11.7%)
0.003
308 (14.2%)
306 (14.1%)
0.003
Osteopenia; n (%)*
256 (34.3%)
247 (33.1%)
0.025
316 (22.3%)
315 (22.2%)
0.002
572 (26.4%)
562 (25.9%)
0.011
History of hip and femur fractures; n (%)*
41 (5.5%)
45 (6.0%)
-0.021
105 (7.4%)
102 (7.2%)
0.008
146 (6.7%)
147 (6.8%)
-0.004
Other Fractures ; n (%)*
90 (12.0%)
95 (12.7%)
-0.021
170 (12.0%)
160 (11.3%)
0.022
260 (12.0%)
255 (11.8%)
0.006
Glucocorticoid-Induced Osteoporosis; n (%)*
2 (0.3%)
2 (0.3%)
0.000
1 (0.1%)
2 (0.1%)
0.000
003 (0.1%)
004 (0.2%)
-0.026
Combined comorbidity score
...mean (sd)
1.20 (2.17)
1.25 (2.25)
-0.023
0.90 (1.71)
0.86 (1.72)
0.023
1.00 (1.88)
0.99 (1.92)
0.005
...median [IQR]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.000
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.000
0.34 (1.88)
0.34 (1.92)
0.000
Frailty Score: Empirical Version 365 days as Categories
...< 0.12908; n (%)
317 (42.4%)
318 (42.6%)
-0.004
476 (33.5%)
472 (33.2%)
0.006
793 (36.6%)
790 (36.5%)
0.002
...0.12908 - 0.1631167; n (%)
158 (21.2%)
155 (20.7%)
0.012
309 (21.8%)
318 (22.4%)
-0.014
467 (21.6%)
473 (21.8%)
-0.005
...>= 0.1631167; n (%)
272 (36.4%)
274 (36.7%)
-0.006
635 (44.7%)
630 (44.4%)
0.006
907 (41.9%)
904 (41.7%)
0.004
Medication Use
Use of oral corticosteroids; n (%)*
268 (35.9%)
266 (35.6%)
0.006
498 (35.1%)
506 (35.6%)
-0.010
766 (35.3%)
772 (35.6%)
-0.006
Use of antidepressants; n (%)*
256 (34.3%)
275 (36.8%)
-0.052
606 (42.7%)
576 (40.6%)
0.043
862 (39.8%)
851 (39.3%)
0.010
Use of anticonvulsants; n (%)*
159 (21.3%)
149 (19.9%)
0.035
323 (22.7%)
311 (21.9%)
0.019
482 (22.2%)
460 (21.2%)
0.024
Use of beta blocker OR calcium channel blocker; n (%)*
250 (33.5%)
235 (31.5%)
0.043
471 (33.2%)
478 (33.7%)
-0.011
721 (33.3%)
713 (32.9%)
0.009
Use of PPIs; n (%)*
222 (29.7%)
219 (29.3%)
0.009
488 (34.4%)
501 (35.3%)
-0.019
710 (32.8%)
720 (33.2%)
-0.009
Use of opioids; n (%)*
419 (56.1%)
420 (56.2%)
-0.002
848 (59.7%)
853 (60.1%)
-0.008
1,267 (58.5%)
1,273 (58.7%)
-0.004
Use of antipsychotics; n (%)*
21 (2.8%)
24 (3.2%)
-0.023
53 (3.7%)
54 (3.8%)
-0.005
074 (3.4%)
078 (3.6%)
-0.011
Use of anxiolytics/hypnotics; n (%)*
74 (9.9%)
88 (11.8%)
-0.061
249 (17.5%)
228 (16.1%)
0.037
323 (14.9%)
316 (14.6%)
0.008
Use of dementia meds; n (%)*
34 (4.6%)
32 (4.3%)
0.015
73 (5.1%)
69 (4.9%)
0.009
107 (4.9%)
101 (4.7%)
0.009
Use of antiparkinsonian meds; n (%)*
21 (2.8%)
26 (3.5%)
-0.040
58 (4.1%)
64 (4.5%)
-0.020
079 (3.6%)
090 (4.2%)
-0.031
Use of Benzodiazepine; n (%)*
146 (19.5%)
162 (21.7%)
-0.054
404 (28.5%)
382 (26.9%)
0.036
550 (25.4%)
544 (25.1%)
0.007
All antidiabetic medications; n (%)*
78 (10.4%)
73 (9.8%)
0.020
162 (11.4%)
166 (11.7%)
-0.009
240 (11.1%)
239 (11.0%)
0.003
ACEI/ARB; n (%)*
261 (34.9%)
256 (34.3%)
0.013
470 (33.1%)
475 (33.5%)
-0.008
731 (33.7%)
731 (33.7%)
0.000
Use of Anticoagulants; n (%)*
71 (9.5%)
72 (9.6%)
-0.003
158 (11.1%)
148 (10.4%)
0.023
229 (10.6%)
220 (10.2%)
0.013
Use of Amiodarone; n (%)
9 (1.2%)
8 (1.1%)
0.009
19 (1.3%)
23 (1.6%)
-0.025
028 (1.3%)
031 (1.4%)
-0.009
Appendix B

Digoxin; n (%)
18 (2.4%)
14 (1.9%)
0.034
45 (3.2%)
38 (2.7%)
0.030
063 (2.9%)
052 (2.4%)
0.031
Use of Diuretics; n (%)*
205 (27.4%)
220 (29.5%)
-0.047
466 (32.8%)
466 (32.8%)
0.000
671 (31.0%)
686 (31.7%)
-0.015
Use of Aspirin; n (%)
5 (0.7%)
5 (0.7%)
0.000
25 (1.8%)
24 (1.7%)
0.008
030 (1.4%)
029 (1.3%)
0.009
NSAIDs (NOT including aspirin); n (%)
203 (27.2%)
188 (25.2%)
0.045
377 (26.5%)
318 (22.4%)
0.096
580 (26.8%)
506 (23.4%)
0.078
HRT (Use of estrogens, progestins, androgens); n (%)*
47 (6.3%)
44 (5.9%)
0.017
84 (5.9%)
93 (6.5%)
-0.025
131 (6.0%)
137 (6.3%)
-0.012
Other Pressors; n (%)
5 (0.7%)
5 (0.7%)
0.000
8 (0.6%)
20 (1.4%)
-0.080
013 (0.6%)
025 (1.2%)
-0.064
Use of Statins ; n (%)*
258 (34.5%)
252 (33.7%)
0.017
521 (36.7%)
523 (36.8%)
-0.002
779 (35.9%)
775 (35.8%)
0.002
Selective Estrogen Receptor Modulators (SERMs); n (%)*
7 (0.9%)
19 (2.5%)
-0.124
31 (2.2%)
38 (2.7%)
-0.032
038 (1.8%)
057 (2.6%)
-0.055
Healthcare Utilization Measures
Use of any drugs claims*
...mean (sd)
24.76 (18.01)
24.95 (18.56)
-0.010
25.89 (19.03)
25.43 (18.22)
0.025
25.50 (18.68)
25.26 (18.34)
0.013
Number of office visits*
...mean (sd)
11.57 (7.84)
11.48 (7.34)
0.012
11.99 (8.51)
11.90 (7.78)
0.011
11.85 (8.29)
11.76 (7.63)
0.011
Number of ED visits*
...mean (sd)
0.69 (1.22)
0.76 (1.17)
-0.059
0.59 (1.19)
0.60 (1.22)
-0.008
0.62 (1.20)
0.66 (1.20)
-0.033
Number of Hospitalizations*
...mean (sd)
0.46 (1.02)
0.46 (1.02)
0.000
2.09 (5.83)
2.09 (5.52)
0.000
1.53 (4.76)
1.53 (4.51)
0.000
Recent hospitalization (-30 days to Index Rx date); n (%)
14 (1.9%)
19 (2.5%)
-0.041
28 (2.0%)
29 (2.0%)
0.000
042 (1.9%)
048 (2.2%)
-0.021
Old hospitalizations (-450 to -31 days); n (%)
163 (21.8%)
167 (22.4%)
-0.014
356 (25.1%)
360 (25.4%)
-0.007
519 (24.0%)
527 (24.3%)
-0.007
Number of Endocrinologist visits*
...mean (sd)
0.41 (1.19)
0.43 (1.11)
-0.017
1.75 (2.89)
1.73 (2.94)
0.007
1.29 (2.44)
1.28 (2.47)
0.004
Number of DXA test performed*
...mean (sd)
0.73 (0.63)
0.73 (0.54)
0.000
0.49 (0.52)
0.49 (0.52)
0.000
0.57 (0.56)
0.57 (0.53)
0.000
Number of hospital days*
...mean (sd)
5.18 (17.50)
4.98 (17.59)
0.011
2.09 (5.83)
2.09 (5.52)
0.000
3.16 (11.30)
3.09 (11.25)
0.006
Occurrence of basic or comprehensive blood chemistry test; n (%)*
577 (77.2%)
573 (76.7%)
0.012
626 (44.1%)
615 (43.3%)
0.016
1,203 (55.5%)
1,188 (54.8%)
0.014
Number of HbA1C test ordered*
...mean (sd)
0.55 (1.09)
0.54 (1.15)
0.009
0.27 (0.78)
0.26 (0.79)
0.013
0.37 (0.90)
0.36 (0.93)
0.011
Flexible Sigmoidoscopy or colonoscopy or CT virtual colonoscopy; n (%)*
64 (8.6%)
68 (9.1%)
-0.018
142 (10.0%)
138 (9.7%)
0.010
206 (9.5%)
206 (9.5%)
0.000
Number of Mammograms (Breast cancer screening); n (%)*
352 (47.1%)
359 (48.1%)
-0.020
547 (38.5%)
545 (38.4%)
0.002
899 (41.5%)
904 (41.7%)
-0.004
Number of Pap smear (Cervical cancer screening); n (%)*
144 (19.3%)
138 (18.5%)
0.020
264 (18.6%)
265 (18.7%)
-0.003
408 (18.8%)
403 (18.6%)
0.005
Flu vaccine; n (%)*
278 (37.2%)
273 (36.5%)
0.015
312 (22.0%)
314 (22.1%)
-0.002
590 (27.2%)
587 (27.1%)
0.002
Pneumococcal vaccine; n (%)*
132 (17.7%)
135 (18.1%)
-0.010
125 (8.8%)
134 (9.4%)
-0.021
257 (11.9%)
269 (12.4%)
-0.015
Copay for pharmacy cost (charges in U.S. $)*
...mean (sd)
36.14 (46.87)
34.80 (42.78)
0.030
21.56 (22.23)
21.55 (23.62)
0.000
26.59 (32.88)
26.12 (31.56)
0.015
...median [IQR]
23.44 [13.37, 42.35]
25.00 [11.82, 41.43]
-0.035
17.18 [7.87, 29.33]
17.29 [8.09, 28.68]
-0.005
19.34 (32.88)
19.95 (31.56)
-0.019
...Missing; n (%)
NA
NA
NA
NA
NA
NA
NA
NA
NA
Business Type*
...Commercial; n (%)
291 (39.0%)
291 (39.0%)
0.000
NA
NA
NA
291 (39.0%)
291 (39.0%)
0.000
...Medicare; n (%)
456 (61.0%)
456 (61.0%)
0.000
NA
NA
NA
456 (61.0%)
456 (61.0%)
0.000
Insurance Plan Type*
...Comprehensive; n (%)
NA
NA
NA
413 (29.1%)
431 (30.4%)
-0.028
413 (29.1%)
431 (30.4%)
-0.028
...HMO; n (%)
NA
NA
NA
97 (6.8%)
104 (7.3%)
-0.020
97 (6.8%)
104 (7.3%)
-0.020
...PPO; n (%)
NA
NA
NA
731 (51.5%)
705 (49.6%)
0.038
731 (51.5%)
705 (49.6%)
0.038
...Others; n (%)
NA
NA
NA
179 (12.6%)
180 (12.7%)
-0.003
179 (12.6%)
180 (12.7%)
-0.003
*Included in the 1:1 PS matching model
Appendix B