Appendix E-1: Baseline Characteristics of Patients with or without Fracture History

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FU ET AL.

BISPHOSPHONATE USE AND THE RISK OF UNDERGOING TOTAL KNEE ARTHROPLASTY IN OSTEOPOROTIC PATIENTS WITH

OSTEOARTHRITIS.ANATIONWIDE COHORT STUDY IN TAIWAN

http://dx.doi.org/10.2106/JBJS.16.00385 Page

1 Appendix E-1: Baseline Characteristics of Patients with or without Fracture History

With Fracture History

(N = 18,492) Without Fracture History

(N = 121,575) P Value

Age* (yr) 73.51 ± 12.4 67.43 ± 12.4 <0.001

Male sex (%) 25.02 24.21 0.0021

Comorbidity (%)

Hypertension 51.52 43.44 <0.001

Diabetes mellitus 27.88 22.11 <0.001

Fall history 0.68 0.11 <0.001

Chronic obstructive lung

disease 6.79 3.46 <0.001

Urinary incontinence 2.47 1.64 <0.001

Parkinson disease 6.04 2.53 <0.001

Chronic mental disorder 0.77 0.40 <0.001

Dementia 10.55 3.97 <0.001

Depression 5.64 4.07 <0.001

Liver disease 9.82 10.88 <0.001

Peripheral vascular disease 1.34 1.27 0.4227

Cerebrovascular disease 7.05 4.42 <0.001

Arthritis 16.65 17.50 0.0041

Chronic kidney disease 6.56 4.06 <0.001

Co-medications (%)

Opiates 15.67 5.69 <0.001

Nonopioid analgesics 83.05 78.00 <0.001

Antipsychotics 16.69 8.94 <0.001

Anxiolytics 62.83 59.49 <0.001

Sedatives 32.02 24.09 <0.001

Corticosteroids 39.88 37.12 <0.001

Diuretics 30.68 20.91 <0.001

Hormone replacement therapy 5.61 6.67 <0.001

Antiepileptic drugs 18.45 13.16 <0.001

NSAIDs 93.65 93.14 0.0109

Antidepressants 21.09 15.06 <0.001

*The values are given as the mean and the standard deviation.

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FU ET AL.

2 Appendix E-2: Results of Fully Adjusted Regression Model of the Risk of Total Knee Arthroplasty

N HR (95% CI) P Value

Total population 140,067 0.71 (0.65-0.78) <0.001

Without fracture history 121,575 0.66 (0.60-0.74) <0.001

With fracture history 18,492 0.91 (0.74-1.11) 0.3646

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FU ET AL.

3 Appendix E-3: Results of Bisphosphonate Use as a Time-Dependent Variable

Unadjusted Model Propensity-Score Adjusted Model

HR (95% CI) P Value HR (95% CI) P Value

Total population (n =

140,067) 0.632 (0.581-0.687) <0.001 0.660 (0.603-0.723) <0.001 Without fracture history (n

= 121,575) 0.687 (0.623-0.756) <0.001 0.613 (0.554-0.679) <0.001 With fracture history (n =

18,492) 0.717 (0.597-0.862) 0.0004 0.824 (0.675-1.005) 0.0565

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FU ET AL.

4 Appendix E-4: Sensitivity Analysis Assessing the Strength of an Unmeasured Confounder Needed to Move the Apparent HR to the Null

In the causal graphs (see below), a factor can be a confounder when it is associated with drug exposure and is also an independent predictor of the study outcome (i.e., disease).

By conducting the “rule out” method

³¹

, we can find all combinations of OR

_EC

(odds ratio for the exposure-confounder association) and RR

_CD

(relative risk for the confounder-disease association) needed for a confounder to fully explain the observed association between exposure and disease.

Exposure

Confounder

Disease

OR

EC

RR

CD

Based on an observed apparent HR (AHR) of 0.76, and assuming that the prevalence of bisphosphonate exposure (P

_E

) is 10% and the prevalence of the confounder (P

_C

) is 30%.

The “x’s” on the yellow line represent all combinations of OR

_EC

and RR

_CD

Appendix E-1: Baseline Characteristics of Patients with or without Fracture History

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