1. Epidemiology and Global Health
  2. Medicine

Association between bisphosphonate use and COVID-19 related outcomes

  1. Jeffrey Thompson
  2. Yidi Wang
  3. Tobias Dreischulte
  4. Olga Barreiro
  5. Rodrigo J Gonzalez
  6. Pavel Hanč
  7. Colette Matysiak
  8. Harold R Neely
  9. Marietta Rottenkolber
  10. Thomas Haskell
  11. Stefan Endres
  12. Ulrich H von Andrian  Is a corresponding author
  1. Cerner Enviza, United States
  2. Dept. of Immunology, Harvard Medical School, United States
  3. Institute of General Practice and Family Medicine, University Hospital of Ludwig Maximilians-University Munich, Germany
  4. Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, University Hospital, LMU Munich, Germany, Germany
https://doi.org/10.7554/eLife.79548
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Cite this article
  1. Jeffrey Thompson
  2. Yidi Wang
  3. Tobias Dreischulte
  4. Olga Barreiro
  5. Rodrigo J Gonzalez
  6. Pavel Hanč
  7. Colette Matysiak
  8. Harold R Neely
  9. Marietta Rottenkolber
  10. Thomas Haskell
  11. Stefan Endres
  12. Ulrich H von Andrian
(2023)
Association between bisphosphonate use and COVID-19 related outcomes
eLife 12:e79548.
https://doi.org/10.7554/eLife.79548
  2. Download BibTeX
  3. Download .RIS
8 figures and 54 tables

Figures

Figure 1
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Study periods, cohort selection, and analyses of BP use on COVID-19-related outcomes.

(A) Schematic overview of the study timeline. (B) Schematic flow diagram illustrating the identification of the study population and matched control populations for primary analysis and sensitivity analyses cohorts. BP: bisphosphonate; CA: California; CCI: Charlson comorbidity index; CI: confidence interval; COPD: chronic obstructive pulmonary disease; FL: Florida; IL: Illinois; NY: New York; OR: odds ratio; PCP: primary care physician; PS: propensity score; PSM: propensity score match.

Figure 2
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Association of BP use and COVID-19-related outcomes incidence (left) and regression-adjusted results for odds (right) of SARS-CoV-2 testing (blue), COVID-19 diagnosis (purple), and COVID-19-related hospitalizations (red) of BP users compared with BP non-users in the all-regions combined primary analysis cohort (i) and when stratified by region/state into: Northeast (ii), Midwest (iii), South (iv), West (v), and New York state (vi).

For details see Figure 2—source data 1.

Figure 2—source data 1

COVID-19-related outcomes in the primary analysis cohort.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig2-data1-v2.xlsx
Figure 3
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Timing of BP use and COVID-19-related outcomes.

(A) Schematic of BP user sub-stratification by timing of exposure to alendronic acid or zoledronic acid prior to outcome assessment. Broken lines represent periods of active BP dosing. For zoledronic acid users, days covered was considered to extend 1 year past the dosing period based on dosing guidelines. (B) Incidence (left) and regression-adjusted results (right) for odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations of BP users compared with BP non-users in pre-specified subgroups. For further details see Figure 3—source data 1. CI: confidence interval; OR: odds ratio.

Figure 3—source data 1

Primary analysis cohort by timing of BP dosing, COVID-19-related outcomes.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig3-data1-v2.xlsx
Figure 4
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COVID-19-related outcomes among the Bone-RX and Osteo-Dx-Rx restricted cohorts.

Incidence and forest plots summarizing regression-adjusted odds ratios of SARS-CoV-2 testing (blue), COVID-19 diagnosis (purple), and COVID-19-related hospitalizations (red) in the (A) ‘Bone-Rx’ (see also Figure 4—source data 1) and (B) ‘Osteo-Dx-Rx’ sensitivity analysis cohorts (see also Figure 4—source data 2).

Figure 4—source data 1

Source data for Figure 4A: Bone-Rx cohort COVID-19-related outcomes.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig4-data1-v2.xlsx
Figure 4—source data 2

Source data for Figure 4B: Osteo-Dx-Rx cohort COVID-19-related outcomes.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig4-data2-v2.xlsx
Figure 5
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Exploratory outcomes among BP users versus BP non-users.

Incidence and adjusted odds ratios of other respiratory infections, in the primary, ‘Bone-Rx’, and ‘Osteo-Dx-Rx’ cohorts. For details, see Figure 5—source data 1. CI: confidence interval; OR: odds ratio.

Figure 5—source data 1

Positive control outcomes by primary, bone-Rx, and osteo-Dx-Rx cohorts.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig5-data1-v2.xlsx
Figure 6
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Association of other preventive drugs with COVID-19-related outcomes.

(A). Schematic illustrating the identification of study populations and matched controls for each drug class. (B–E) Incidence and adjusted odds ratios of SARS-CoV-2 testing (blue), COVID-19 diagnosis (purple), and COVID-19-related hospitalizations (red) in users and non-users of (B) statins (see also Figure 6—source data 1), (C) antihypertensive medications (see also Figure 6—source data 2), (D) non-insulin antidiabetic medications (see also Figure 6—source data 3), and (E) antidepressant medications (see also Figure 6—source data 4). For each class of preventive medications, further analysis was performed comparing BP users and BP non-users within matched cohorts of medication users (middle) and medication non-users (bottom). BP: bisphosphonate; CCI: Charlson comorbidity index; CI: confidence interval; COPD: chronic obstructive pulmonary disease; OR: odds ratio; PCP: primary care physician; PS: propensity score; PSM: propensity score match.

Figure 6—source data 1

Source data for Figure 6B: COVID-19-related outcomes by statin use overall & sub-stratified by BP use.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig6-data1-v2.xlsx
Figure 6—source data 2

Source data for Figure 6C: COVID-19-related outcomes by antihypertensive use overall & sub-stratified by BP use.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig6-data2-v2.xlsx
Figure 6—source data 3

Source data for Figure 6D: COVID-19-related outcomes by antidiabetic use overall & sub-stratified by BP use.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig6-data3-v2.xlsx
Figure 6—source data 4

Source data for Figure 6E: COVID-19-related outcomes by antidepressant use overall & sub-stratified by BP use.

https://cdn.elifesciences.org/articles/79548/elife-79548-fig6-data4-v2.xlsx
Appendix 3—figure 1
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Full cohort: dds ratio by additional number of BP users classified as having COVID-19 diagnosis.Forest plot of the change in the crude odds ratio (OR) of BP users having a COVID-19 diagnosis as a factor of the additional number of BP users needed to be classified as having a COVID-19 diagnosis to reach statistical non-significance for all observations.
Appendix 3—figure 2
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Bone-Rx cohort: odds ratio by additional number of BP users classified as having COVID-19 diagnosis.

Forest plot of the change in the crude odds ratio (OR) of BP users having a COVID-19 diagnosis as a factor of the additional number of BP users needed to be classified as having a COVID-19 diagnosis to reach statistical non-significance when comparing BP users to users of non-BP anti-resorptive bone medication

Tables

Table 1
Most recent bisphosphonate claim among all users.
Drug (route)N%
Alendronate / alendronic acid (oral)340,81075.4%
Etidronate (oral)140.0%
Ibandronate / ibandronic acid (oral)37,9888.4%
Ibandronic acid (injection/infusion)11690.3%
Pamidronate (injection/infusion)11210.2%
Risedronate (oral)18,9914.2%
Zoledronic acid (injection/infusion)51,95811.5%
Table 2
Primary analysis cohort (all regions), patient characteristics pre/post match.
All Observations UnmatchedAll Observations Matched
AllBP Non-usersBP Usersp-valueAllBP Non-usersBP Usersp-value
N%N%N%N%N%N%
All Patients7,906,603100.00%7,454,55294.30%452,0515.70%900,732100.00%450,36650.00%450,36650.00%
Demographics
Age
 ≤201,840,05023.30%1,838,92224.70%1,1280.20%<0.0012,2530.30%1,1250.20%1,1280.30%1
 21-401,446,99918.30%1,443,90819.40%3,0910.70%6,1950.70%3,1040.70%3,0910.70%
 41-50925,30911.70%916,75812.30%8,5511.90%17,0961.90%8,5451.90%8,5511.90%
 51-601,250,19015.80%1,184,46915.90%65,72114.50%131,44514.60%65,72414.60%65,72114.60%
 61-701,181,26114.90%1,024,38313.70%156,87834.70%313,82234.80%156,94434.80%156,87834.80%
 71-80783,7759.90%642,0508.60%141,72531.40%280,80331.20%140,36631.20%140,43731.20%
 ≥81479,0196.10%404,0625.40%74,95716.60%149,11816.60%74,55816.60%74,56016.60%
Gender
 Female4,670,96059.10%4,263,52457.20%407,43690.10%<0.001811,49790.10%405,74690.10%405,75190.10%0.99
 Male3,235,64340.90%3,191,02842.80%44,6159.90%89,2359.90%44,6209.90%44,6159.90%
Region
 Midwest1,467,80218.60%1,391,83518.70%75,96716.80%<0.001151,80216.90%75,90116.90%75,90116.90%1
 Northeast2,152,56027.20%2,032,83227.30%119,72826.50%238,98826.50%119,49426.50%119,49426.50%
 South3,042,60438.50%2,881,71838.70%160,88635.60%319,40835.50%159,70435.50%159,70435.50%
 West1,243,63715.70%1,148,16715.40%95,47021.10%190,53421.20%95,26721.20%95,26721.20%
Insurance
 Commercial3,938,60349.80%3,791,54550.90%147,05832.50%<0.001294,07032.60%147,01232.60%147,05832.70%1
 Dual156,4972.00%125,0901.70%31,4076.90%59,9366.70%29,9806.70%29,9566.70%
 Medicaid2,594,50032.80%2,517,02033.80%77,48017.10%154,51917.20%77,27217.20%77,24717.20%
 Medicare1,217,00315.40%1,020,89713.70%196,10643.40%392,20743.50%196,10243.50%196,10543.50%
PCP Visit 2019
 No4,283,69754.20%4,119,83155.30%163,86636.20%<0.001327,38336.30%163,65936.30%163,72436.40%0.89
 Yes3,622,90645.80%3,334,72144.70%288,18563.80%573,34963.70%286,70763.70%286,64263.60%
Clinical Characteristics
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.621.380.61.350.951.76<0.0010.951.760.951.760.951.760.7
Regression Comorbidity Covariates
N%N%N%p-valueN%N%N%p-value
Osteoporosis267,0203.40%135,2311.80%131,78929.20%<0.001163,81418.20%32,3907.20%131,42429.20%<0.001
Cancer419,0835.30%366,7864.90%52,29711.60%<0.00194,14810.50%41,8619.30%52,28711.60%<0.001
CKD/ESRD361,4514.60%328,6334.40%32,8187.30%<0.00168,9997.70%36,1828.00%32,8177.30%<0.001
COPD466,0945.90%427,8505.70%38,2448.50%<0.00184,2349.40%45,99010.20%38,2448.50%<0.001
CVD1,084,03113.70%999,52613.40%84,50518.70%<0.001197,24321.90%112,93325.10%84,31018.70%<0.001
Dementia125,8111.60%113,7781.50%12,0332.70%<0.00124,9212.80%12,8892.90%12,0322.70%<0.001
Depression571,3037.20%531,3557.10%39,9488.80%<0.00186,2809.60%46,43110.30%39,8498.80%<0.001
Dyslipidemia1,532,25419.40%1,375,92018.50%156,33434.60%<0.001322,12535.80%166,36036.90%155,76534.60%<0.001
HIV/AIDS33,2290.40%31,7110.40%15180.30%<0.00128970.30%13790.30%1,5180.30%0.01
Hypertension1,899,06324.00%1,723,51923.10%175,54438.80%<0.001384,05942.60%209,18446.40%174,87538.80%<0.001
Liver Disease251,3313.20%231,6643.10%19,6674.40%<0.00138,6974.30%19,0314.20%19,6664.40%0.001
Obesity638,5068.10%608,0838.20%30,4236.70%<0.00176,8448.50%46,49810.30%30,3466.70%<0.001
Sickle Cell Anemia10,4990.10%10,2920.10%2070.00%<0.0014220.00%2150.00%2070.00%0.7
Stroke104,8591.30%97,0011.30%7,8581.70%<0.00119,3952.20%11,5692.60%7,8261.70%<0.001
Type 2 Diabetes978,23912.40%895,98312.00%82,25618.20%<0.001184,97820.50%103,03122.90%81,94718.20%<0.001
Appendix 2—table 1
Primary Analysis Cohort (Region=Northeast), Patient Characteristics Pre/Post Match.
Region=Northeast UnmatchedRegion=Northeast Matched
AllBP Non-usersBP Usersp-valueAllBP Non-usersBP Usersp-value
N%N%N%N%N%N%
All Patients2,152,560100.00%2,032,83294.40%119,7285.60%238,988100.00%119,49450.00%119,49450.00%
Age
 ≤20363,63716.90%363,40117.90%2360.20%<0.0014740.20%2380.20%2360.20%1
 21-40397,37718.50%396,61319.50%7640.60%1,5280.60%7640.60%7640.60%
 41-50261,57012.20%259,52812.80%2,0421.70%4,0841.70%2,0421.70%2,0421.70%
 51-60372,23817.30%354,22817.40%18,01015.00%36,02015.10%18,01015.10%18,01015.10%
 61-70354,33116.50%313,23715.40%41,09434.30%82,23334.40%41,13934.40%41,09434.40%
 71-80252,71211.70%215,15110.60%37,56131.40%74,83131.30%37,39331.30%37,43831.30%
 ≥81150,6957.00%130,6746.40%20,02116.70%39,81816.70%19,90816.70%19,91016.70%
Gender
 Female1,275,61159.30%1,167,24157.40%108,37090.50%<0.001216,27390.50%108,13790.50%108,13690.50%0.99
 Male876,94940.70%865,59142.60%11,3589.50%22,7159.50%11,3579.50%11,3589.50%
Insurance
 Commercial1,050,79548.80%1,017,50250.10%33,29327.80%<0.00166,55227.80%33,25927.80%33,29327.90%0.99
 Dual47,7732.20%40,1682.00%7,6056.40%15,1146.30%7,5766.30%7,5386.30%
 Medicaid631,86329.40%608,64929.90%23,21419.40%46,09419.30%23,04719.30%23,04719.30%
 Medicare422,12919.60%366,51318.00%55,61646.50%111,22846.50%55,61246.50%55,61646.50%
PCP Visit 2019
 No1,212,39456.30%1,162,52757.20%49,86741.70%<0.00199,74141.70%49,87441.70%49,86741.70%0.98
 Yes940,16643.70%870,30542.80%69,86158.30%139,24758.30%69,62058.30%69,62758.30%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.671.420.651.40.931.71<0.0010.931.710.931.710.931.710.96

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 2
Primary Analysis Cohort (Region=Midwest), Patient Characteristics Pre/Post Match.
Region=Midwest UnmatchedRegion=Midwest Matched
AllBP Non-usersBP Usersp-valueAllBP Non-usersBP Usersp-value
N%N%N%N%N%N%
All Patients1,467,802100.0%1,391,83594.8%75,9675.2%151,802100.0%75,90150.0%75,90150.0%
Age
 ≤20310,02721.1%309,75922.3%2680.4%<0.0015370.4%2690.4%2680.4%1.00
 21-40287,23619.6%286,64320.6%5930.8%1,1880.8%5950.8%5930.8%
 41-50185,24012.6%183,55613.2%1,6842.2%3,3672.2%1,6832.2%1,6842.2%
 51-60246,23016.8%233,99216.8%12,23816.1%24,47816.1%12,24016.1%12,23816.1%
 61-70224,66815.3%196,17214.1%28,49637.5%56,99137.5%28,49537.5%28,49637.5%
 71-80130,5638.9%109,4427.9%21,12127.8%42,15327.8%21,07527.8%21,07827.8%
 ≥8183,8385.7%72,2715.2%11,56715.2%23,08815.2%11,54415.2%11,54415.2%
Gender
 Female863,15658.8%794,57857.1%68,57890.3%<0.001137,02890.3%68,51690.3%68,51290.3%0.97
 Male604,64641.2%597,25742.9%7,3899.7%14,7749.7%7,3859.7%7,3899.7%
Insurance
 Commercial885,65160.3%854,51861.4%31,13341.0%<0.00162,24341.0%31,11041.0%31,13341.0%1.00
 Dual28,1901.9%24,5841.8%3,6064.7%7,2114.8%3,6054.7%3,6064.8%
 Medicaid318,59621.7%310,47322.3%8,12310.7%16,13610.6%8,07910.6%8,05710.6%
 Medicare235,36516.0%202,26014.5%33,10543.6%66,21243.6%33,10743.6%33,10543.6%
PCP Visit 2019
 No711,30848.5%682,60149.0%28,70737.8%<0.00157,39837.8%28,69137.8%28,70737.8%0.93
 Yes756,49451.5%709,23451.0%47,26062.2%94,40462.2%47,21062.2%47,19462.2%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.591.370.561.340.991.86<0.0010.991.860.991.851.001.860.77

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 3
Primary Analysis Cohort (Region=South), Patient Characteristics Pre/Post Match.
Region=South UnmatchedRegion=South Matched
AllBP Non-usersBP Usersp-valueAllBP Non-usersBP Usersp-value
N%N%N%N%N%N%
All Patients3,042,604100.0%2,881,71894.7%160,8865.3%319,408100.0%159,70450.0%159,70450.0%
Age
 ≤20890,67729.3%890,20330.9%4740.3%<0.0019430.3%4690.3%4740.3%1.00
 21-40527,97117.4%526,79418.3%1,1770.7%2,3640.7%1,1870.7%1,1770.7%
 41-50338,26211.1%334,84111.6%3,4212.1%6,8392.1%3,4182.1%3,4212.1%
 51-60442,75714.6%417,66414.5%25,09315.6%50,18615.7%25,09315.7%25,09315.7%
 61-70409,85413.5%353,95812.3%55,89634.7%111,80035.0%55,90435.0%55,89635.0%
 71-80272,7619.0%222,1567.7%50,60531.5%99,22331.1%49,60531.1%49,61831.1%
 ≥81160,3225.3%136,1024.7%24,22015.1%48,05315.0%24,02815.0%24,02515.0%
Gender
 Female1,800,16659.2%1,654,35157.4%145,81590.6%<0.001289,26390.6%144,63090.6%144,63390.6%0.99
 Male1,242,43840.8%1,227,36742.6%15,0719.4%30,1459.4%15,0749.4%15,0719.4%
Insurance
 Commercial1,475,45648.5%1,416,16649.1%59,29036.9%<0.001118,58737.1%59,29737.1%59,29037.1%1.00
 Dual53,4741.8%39,4141.4%14,0608.7%25,7528.1%12,8748.1%12,8788.1%
 Medicaid1,121,60636.9%1,099,95738.2%21,64913.5%43,29913.6%21,65013.6%21,64913.6%
 Medicare392,06812.9%326,18111.3%65,88741.0%131,77041.3%65,88341.3%65,88741.3%
PCP Visit 2019
 No1,701,04055.9%1,646,57257.1%54,46833.9%<0.001108,60134.0%54,27534.0%54,32634.0%0.85
 Yes1,341,56444.1%1,235,14642.9%106,41866.1%210,80766.0%105,42966.0%105,37866.0%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.571.310.551.280.861.70<0.0010.861.700.861.700.861.710.84

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 4
Primary Analysis Cohort (Region=West), Patient Characteristics Pre/Post Match.
Region=West UnmatchedRegion=West Matched
AllBP Non-usersBP Usersp-valueAllBP Non-usersBP Usersp-value
N%N%N%N%N%N%
All Patients1,243,637100.0%1,148,16792.3%95,4707.7%190,534100.0%95,26750.0%95,26750.0%
Age
 ≤20275,70922.2%275,55924.0%1500.2%<0.0012990.2%1490.2%1500.2%1.00
 21-40234,41518.8%233,85820.4%5570.6%1,1150.6%5580.6%5570.6%
 41-50140,23711.3%138,83312.1%1,4041.5%2,8061.5%1,4021.5%1,4041.5%
 51-60188,96515.2%178,58515.6%10,38010.9%20,76110.9%10,38110.9%10,38010.9%
 61-70192,40815.5%161,01614.0%31,39232.9%62,79833.0%31,40633.0%31,39233.0%
 71-80127,73910.3%95,3018.3%32,43834.0%64,59633.9%32,29333.9%32,30333.9%
 ≥8184,1646.8%65,0155.7%19,14920.1%38,15920.0%19,07820.0%19,08120.0%
Gender
 Female732,02758.9%647,35456.4%84,67388.7%<0.001168,93388.7%84,46388.7%84,47088.7%0.96
 Male511,61041.1%500,81343.6%10,79711.3%21,60111.3%10,80411.3%10,79711.3%
Insurance
 Commercial526,70142.4%503,35943.8%23,34224.4%<0.00146,68824.5%23,34624.5%23,34224.5%1.00
 Dual27,0602.2%20,9241.8%6,1366.4%11,8596.2%5,9256.2%5,9346.2%
 Medicaid522,43542.0%497,94143.4%24,49425.7%48,99025.7%24,49625.7%24,49425.7%
 Medicare167,44113.5%125,94311.0%41,49843.5%82,99743.6%41,50043.6%41,49743.6%
PCP Visit 2019
 No658,95553.0%628,13154.7%30,82432.3%<0.00161,64332.4%30,81932.4%30,82432.4%0.98
 Yes584,68247.0%520,03645.3%64,64667.7%128,89167.6%64,44867.6%64,44367.6%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.691.460.661.421.081.84<0.0011.091.831.081.831.091.840.73

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 5
Primary Analysis Cohort (Region=New York State), Patient Characteristics Pre/Post Match.
Region=New York State UnmatchedRegion=New York State Matched
AllBP Non-usersBP Usersp-valueAllBP Non-usersBP Usersp-value
N%N%N%N%N%N%
All Patients968,296100.0%918,26194.8%50,0355.2%99,724100.0%49,86250.0%49,86250.0%
Age
≤20133,17813.8%133,12814.5%500.1%<0.0011020.1%520.1%500.1%1.00
21-40192,95919.9%192,73121.0%2280.5%4530.5%2250.5%2280.5%
41-50127,79413.2%127,13913.8%6551.3%1,3111.3%6561.3%6551.3%
51-60172,44417.8%166,08018.1%6,36412.7%12,73212.8%6,36812.8%6,36412.8%
61-70159,91216.5%143,77615.7%16,13632.2%32,26532.4%16,12932.3%16,13632.4%
71-80120,11712.4%102,65511.2%17,46234.9%34,69334.8%17,35234.8%17,34134.8%
≥8161,8926.4%52,7525.7%9,14018.3%18,16818.2%9,08018.2%9,08818.2%
Gender
Female573,61059.2%528,15257.5%45,45890.9%<0.00190,56790.8%45,28290.8%45,28590.8%0.97
Male394,68640.8%390,10942.5%4,5779.1%9,1579.2%4,5809.2%4,5779.2%
Insurance
Commercial500,91851.7%490,50353.4%10,41520.8%<0.00120,83020.9%10,41520.9%10,41520.9%1.00
Dual6,8140.7%5,2180.6%1,5963.2%3,1543.2%1,5813.2%1,5733.2%
Medicaid252,36626.1%243,19126.5%9,17518.3%18,04418.1%9,01918.1%9,02518.1%
Medicare208,19821.5%179,34919.5%28,84957.7%57,69657.9%28,84757.9%28,84957.9%
PCP Visit 2019
No521,28253.8%502,60954.7%18,67337.3%<0.00137,25337.4%18,61637.3%18,63737.4%0.89
Yes447,01446.2%415,65245.3%31,36262.7%62,47162.6%31,24662.7%31,22562.6%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.651.390.631.370.951.68<0.0010.951.680.951.670.951.680.93

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 6
Unadjusted COVID-19-Related Outcomes Stratified by Age, Sex, & Age by Sex; Matched Primary Analysis Cohort, All-Regions Combined.
Primary Analysis Cohort, All Regions Matched
AllSARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
N%N%ORp-valueN%ORp-valueN%ORp-value
LLULLLULLLUL
All Patients900,732100.0%28,1373.1%16,2891.8%3,7100.4%
BP User450,36650.0%5,1891.2%0.22<0.0013,0240.7%0.22<0.0017150.2%0.24<0.001
BP Non-user450,36650.0%22,9485.1%0.210.2213,2652.9%0.210.232,9950.7%0.220.26
By Age
Age ≤202,253100.0%673.0%140.6%20.1%
BP User1,12850.1%292.6%0.750.2620.2%0.160.00720.2%NANA
BP Non-user1,12549.9%383.4%0.461.23121.1%0.040.7400.0%NANA
Age 21-406,195100.0%3355.4%1151.9%130.2%
BP User3,09149.9%581.9%0.20<0.001150.5%0.15<0.00140.1%0.450.27
BP Non-user3,10450.1%2778.9%0.150.261003.2%0.080.2590.3%0.141.45
Age 41-5017,096100.0%8945.2%2701.6%540.3%
BP User8,55150.0%1882.2%0.25<0.001480.6%0.21<0.001140.2%0.35<0.001
BP Non-user8,54550.0%7068.3%0.210.292222.6%0.150.29400.5%0.190.64
Age 51-60131,445100.0%5,7654.4%2,3711.8%3970.3%
BP User65,72150.0%1,1041.7%0.22<0.0014560.7%0.23<0.001830.1%0.26<0.001
BP Non-user65,72450.0%4,6617.1%0.210.241,9152.9%0.210.263140.5%0.210.34
Age 61-70313,822100.0%10,4383.3%5,0291.6%1,0350.3%
BP User156,87850.0%1,8431.2%0.21<0.0019390.6%0.23<0.0011730.1%0.20<0.001
BP Non-user156,94450.0%8,5955.5%0.200.224,0902.6%0.210.248620.5%0.170.24
Age 71-80280,803100.0%7,1792.6%4,8271.7%1,2120.4%
BP User140,43750.0%1,3090.9%0.22<0.0018770.6%0.22<0.0012340.2%0.24<0.001
BP Non-user140,36650.0%5,8704.2%0.200.233,9502.8%0.200.239780.7%0.210.27
Age ≥81149,118100.0%3,4592.3%3,6632.5%9970.7%
BP User74,56050.0%6580.9%0.23<0.0016870.9%0.22<0.0012050.3%0.26<0.001
BP Non-user74,55850.0%2,8013.8%0.210.252,9764.0%0.210.247921.1%0.220.30
Female Patients811,497100.0%24,9363.1%14,3671.8%3,1270.4%
BP User405,75150.0%4,5191.1%0.21<0.0012,6670.7%0.22<0.0015930.1%0.23<0.001
BP Non-user405,74650.0%20,4175.0%0.210.2211,7002.9%0.210.232,5340.6%0.210.25
By Age
Age ≤20885100.0%262.9%70.8%10.1%
BP User44249.9%112.5%0.730.4310.2%0.170.1210.2%NANA
BP Non-user44350.1%153.4%0.331.6061.4%0.021.3800.0%NANA
Age 21-403,765100.0%2185.8%641.7%90.2%
BP User1,87949.9%402.1%0.21<0.001120.6%0.23<0.00130.2%0.500.51
BP Non-user1,88650.1%1789.4%0.150.30522.8%0.120.4360.3%0.132.01
Age 41-5013,542100.0%7305.4%2061.5%370.3%
BP User6,77450.0%1572.3%0.26<0.001430.6%0.26<0.001110.2%0.420.01
BP Non-user6,76850.0%5738.5%0.210.311632.4%0.180.36260.4%0.210.85
Age 51-60119,205100.0%5,2004.4%2,0931.8%3270.3%
BP User59,60250.0%9731.6%0.22<0.0013990.7%0.23<0.001640.1%0.24<0.001
BP Non-user59,60350.0%4,2277.1%0.200.231,6942.8%0.210.262630.4%0.180.32
Age 61-70290,276100.0%9,4743.3%4,5061.6%8850.3%
BP User145,13150.0%1,6391.1%0.20<0.0018510.6%0.23<0.0011440.1%0.19<0.001
BP Non-user145,14550.0%7,8355.4%0.190.213,6552.5%0.210.257410.5%0.160.23
Age 71-80253,094100.0%6,3042.5%4,2541.7%1,0260.4%
BP User126,55950.0%1,1400.9%0.21<0.0017690.6%0.22<0.0011930.2%0.23<0.001
BP Non-user126,53550.0%5,1644.1%0.200.233,4852.8%0.200.238330.7%0.200.27
Age ≥81130,730100.0%2,9842.3%3,2372.5%8420.6%
BP User65,36450.0%5590.9%0.22<0.0015920.9%0.22<0.0011770.3%0.26<0.001
BP Non-user65,36650.0%2,4253.7%0.200.252,6454.0%0.200.246651.0%0.220.31
Male Patients89,235100.0%3,2013.6%1,9222.2%5830.7%
BP User44,61550.0%6701.5%0.25<0.0013570.8%0.22<0.0011220.3%0.26<0.001
BP Non-user44,62050.0%2,5315.7%0.230.281,5653.5%0.200.254611.0%0.220.32
By Age
Age ≤201,368100.0%413.0%70.5%10.1%
BP User68650.1%182.6%0.770.4210.1%0.160.0710.1%NANA
BP Non-user68249.9%233.4%0.411.4460.9%0.021.3700.0%NANA
Age 21-402,430100.0%1174.8%512.1%40.2%
BP User1,21249.9%181.5%0.17<0.00130.2%0.06<0.00110.1%0.330.63
BP Non-user1,21850.1%998.1%0.100.28483.9%0.020.1930.2%0.033.22
Age 41-503,554100.0%1644.6%641.8%170.5%
BP User1,77750.0%311.7%0.22<0.00150.3%0.08<0.00130.2%0.210.01
BP Non-user1,77750.0%1337.5%0.150.33593.3%0.030.21140.8%0.060.74
Age 51-6012,240100.0%5654.6%2782.3%700.6%
BP User6,11950.0%1312.1%0.29<0.001570.9%0.25<0.001190.3%0.37<0.001
BP Non-user6,12150.0%4347.1%0.240.352213.6%0.190.34510.8%0.220.63
Age 61-7023,546100.0%9644.1%5232.2%1500.6%
BP User11,74749.9%2041.7%0.26<0.001880.7%0.20<0.001290.2%0.24<0.001
BP Non-user11,79950.1%7606.4%0.220.304353.7%0.160.251211.0%0.160.36
Age 71-8027,709100.0%8753.2%5732.1%1860.7%
BP User13,87850.1%1691.2%0.23<0.0011080.8%0.23<0.001410.3%0.28<0.001
BP Non-user13,83149.9%7065.1%0.190.274653.4%0.180.281451.0%0.200.40
Age ≥8118,388100.0%4752.6%4262.3%1550.8%
BP User9,19650.0%991.1%0.26<0.001951.0%0.28<0.001280.3%0.22<0.001
BP Non-user9,19250.0%3764.1%0.200.323313.6%0.220.351271.4%0.140.33

  1. BP: bisphosphonate; LL: lower 95% confidence interval level; NA: not applicable; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 7
Unadjusted COVID-19-Related Outcomes Stratified by Age, Sex, & Age by Sex; Matched Primary Analysis Cohort, Region=Northeast.
Region=Northeast Matched
AllSARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
N%N%ORp-valueN%ORp-valueN%ORp-value
LLULLLULLLUL
All Patients238,988100.0%8,8313.7%7,8203.3%1,5050.6%
BP User119,49450.0%1,6841.4%0.22<0.0011,5781.3%0.24<0.0013140.3%0.26<0.001
BP Non-user119,49450.0%7,1476.0%0.210.246,2425.2%0.230.261,1911.0%0.230.30
By Age
Age ≤20474100.0%143.0%71.5%20.4%
BP User23649.8%73.0%1.010.9920.8%0.400.4520.8%NANA
BP Non-user23850.2%72.9%0.352.9252.1%0.082.0700.0%NANA
Age 21-401,528100.0%936.1%553.6%50.3%
BP User76450.0%141.8%0.16<0.00170.9%0.14<0.00110.1%0.250.37
BP Non-user76450.0%7910.3%0.090.29486.3%0.060.3140.5%0.032.23
Age 41-504,084100.0%2345.7%1182.9%180.4%
BP User2,04250.0%532.6%0.27<0.001170.8%0.16<0.00160.3%0.500.16
BP Non-user2,04250.0%1818.9%0.200.371014.9%0.100.27120.6%0.191.33
Age 51-6036,020100.0%1,8635.2%1,1903.3%1600.4%
BP User18,01050.0%3532.0%0.22<0.0012371.3%0.24<0.001380.2%0.31<0.001
BP Non-user18,01050.0%1,5108.4%0.190.259535.3%0.210.281220.7%0.220.45
Age 61-7082,233100.0%3,2003.9%2,4242.9%4030.5%
BP User41,09450.0%5971.5%0.22<0.0015071.2%0.26<0.001790.2%0.24<0.001
BP Non-user41,13950.0%2,6036.3%0.200.241,9174.7%0.230.283240.8%0.190.31
Age 71-8074,831100.0%2,2663.0%2,3063.1%4930.7%
BP User37,43850.0%4421.2%0.23<0.0014751.3%0.25<0.001990.3%0.25<0.001
BP Non-user37,39350.0%1,8244.9%0.210.261,8314.9%0.230.283941.1%0.200.31
Age ≥8139,818100.0%1,1612.9%1,7204.3%4241.1%
BP User19,91050.0%2181.1%0.22<0.0013331.7%0.23<0.001890.4%0.26<0.001
BP Non-user19,90850.0%9434.7%0.190.261,3877.0%0.200.263351.7%0.210.33
Female Patients216,273100.0%7,8973.7%6,9413.2%1,2630.6%
BP User108,13650.0%1,4831.4%0.22<0.0011,3921.3%0.24<0.0012550.2%0.25<0.001
BP Non-user108,13750.0%6,4145.9%0.210.235,5495.1%0.230.261,0080.9%0.220.29
By Age
Age ≤20180100.0%42.2%31.7%10.6%
BP User9050.0%22.2%1.001.0011.1%0.491.0011.1%NANA
BP Non-user9050.0%22.2%0.147.2622.2%0.045.5500.0%NANA
Age 21-40864100.0%596.8%323.7%40.5%
BP User43149.9%102.3%0.19<0.00161.4%0.22<0.00110.2%0.330.62
BP Non-user43350.1%4911.3%0.090.37266.0%0.090.5430.7%0.033.22
Age 41-503,176100.0%1765.5%872.7%130.4%
BP User1,58850.0%402.5%0.28<0.001150.9%0.20<0.00150.3%0.620.40
BP Non-user1,58850.0%1368.6%0.190.40724.5%0.110.3580.5%0.201.91
Age 51-6032,612100.0%1,6905.2%1,0483.2%1250.4%
BP User16,30650.0%3101.9%0.21<0.0012061.3%0.24<0.001310.2%0.33<0.001
BP Non-user16,30650.0%1,3808.5%0.180.248425.2%0.200.27940.6%0.220.49
Age 61-7076,403100.0%2,9333.8%2,1812.9%3430.4%
BP User38,20050.0%5361.4%0.21<0.0014561.2%0.26<0.001630.2%0.22<0.001
BP Non-user38,20350.0%2,3976.3%0.190.231,7254.5%0.230.282800.7%0.170.29
Age 71-8067,857100.0%2,0213.0%2,0633.0%4160.6%
BP User33,93050.0%3931.2%0.23<0.0014131.2%0.24<0.001770.2%0.23<0.001
BP Non-user33,92750.0%1,6284.8%0.210.261,6504.9%0.220.273391.0%0.180.29
Age ≥8135,181100.0%1,0142.9%1,5274.3%3611.0%
BP User17,59150.0%1921.1%0.23<0.0012951.7%0.23<0.001770.4%0.27<0.001
BP Non-user17,59050.0%8224.7%0.190.261,2327.0%0.200.262841.6%0.210.34
Male Patients22,715100.0%9344.1%8793.9%2421.1%
BP User11,35850.0%2011.8%0.26<0.0011861.6%0.26<0.001590.5%0.32<0.001
BP Non-user11,35750.0%7336.5%0.220.316936.1%0.220.301831.6%0.240.43
By Age
Age ≤20294100.0%103.4%41.4%10.3%
BP User14649.7%53.4%1.010.9810.7%0.330.6210.7%NANA
BP Non-user14850.3%53.4%0.293.5832.0%0.033.2400.0%NANA
Age 21-40664100.0%345.1%233.5%10.2%
BP User33350.2%41.2%0.12<0.00110.3%0.04<0.00100.0%NANA
BP Non-user33149.8%309.1%0.040.35226.6%0.010.3210.3%NANA
Age 41-50908100.0%586.4%313.4%50.6%
BP User45450.0%132.9%0.27<0.00120.4%0.06<0.00110.2%0.250.37
BP Non-user45450.0%459.9%0.140.50296.4%0.020.2740.9%0.032.23
Age 51-603,408100.0%1735.1%1424.2%351.0%
BP User1,70450.0%432.5%0.31<0.001311.8%0.27<0.00170.4%0.25<0.001
BP Non-user1,70450.0%1307.6%0.220.451116.5%0.180.40281.6%0.110.57
Age 61-705,830100.0%2674.6%2434.2%601.0%
BP User2,89449.6%612.1%0.29<0.001511.8%0.26<0.001160.6%0.37<0.001
BP Non-user2,93650.4%2067.0%0.210.381926.5%0.190.35441.5%0.210.65
Age 71-806,974100.0%2453.5%2433.5%771.1%
BP User3,50850.3%491.4%0.24<0.001621.8%0.33<0.001220.6%0.39<0.001
BP Non-user3,46649.7%1965.7%0.170.321815.2%0.240.44551.6%0.240.64
Age ≥814,637100.0%1473.2%1934.2%631.4%
BP User2,31950.0%261.1%0.21<0.001381.6%0.23<0.001120.5%0.23<0.001
BP Non-user2,31850.0%1215.2%0.130.321556.7%0.160.33512.2%0.120.43

  1. BP: bisphosphonate; LL: lower 95% confidence interval level; NA: not applicable; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 8
Unadjusted COVID-19-Related Outcomes Stratified by Age, Sex, & Age by Sex; Matched Primary Analysis Cohort, Region=Midwest.
Region=Midwest Matched
AllSARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
N%N%ORp-valueN%ORp-valueN%ORp-value
LLULLLULLLUL
All Patients151,802100.0%4,4512.9%2,0991.4%6360.4%
BP User75,90150.0%8681.1%0.23<0.0013830.5%0.22<0.0011210.2%0.23<0.001
BP Non-user75,90150.0%3,5834.7%0.220.251,7162.3%0.200.255150.7%0.190.29
By Age
Age ≤20537100.0%152.8%20.4%00.0%
BP User26849.9%62.2%0.660.4400.0%NANA00.0%NANA
BP Non-user26950.1%93.3%0.231.8920.7%NANA00.0%NANA
Age 21-401,188100.0%625.2%171.4%10.1%
BP User59349.9%71.2%0.12<0.00120.3%0.130.00200.0%NANA
BP Non-user59550.1%559.2%0.050.26152.5%0.030.5710.2%NANA
Age 41-503,367100.0%1845.5%461.4%160.5%
BP User1,68450.0%362.1%0.23<0.001100.6%0.27<0.00120.1%0.140.002
BP Non-user1,68350.0%1488.8%0.160.33362.1%0.140.55140.8%0.030.62
Age 51-6024,478100.0%9513.9%2931.2%800.3%
BP User12,23850.0%1801.5%0.22<0.001520.4%0.21<0.001150.1%0.23<0.001
BP Non-user12,24050.0%7716.3%0.190.262412.0%0.160.29650.5%0.130.40
Age 61-7056,991100.0%1,7643.1%6711.2%1890.3%
BP User28,49650.0%3221.1%0.21<0.0011230.4%0.22<0.001350.1%0.23<0.001
BP Non-user28,49550.0%1,4425.1%0.190.245481.9%0.180.271540.5%0.160.33
Age 71-8042,153100.0%1,0092.4%5771.4%2000.5%
BP User21,07850.0%2091.0%0.25<0.001950.5%0.19<0.001370.2%0.23<0.001
BP Non-user21,07550.0%8003.8%0.220.304822.3%0.160.241630.8%0.160.32
Age ≥8123,088100.0%4662.0%4932.1%1500.6%
BP User11,54450.0%1080.9%0.30<0.0011010.9%0.25<0.001320.3%0.27<0.001
BP Non-user11,54450.0%3583.1%0.240.373923.4%0.200.311181.0%0.180.40
Female Patients137,028100.0%3,9452.9%1,8281.3%5430.4%
BP User68,51250.0%7621.1%0.23<0.0013330.5%0.22<0.0011030.2%0.23<0.001
BP Non-user68,51650.0%3,1834.6%0.210.251,4952.2%0.190.254400.6%0.190.29
By Age
Age ≤20226100.0%73.1%10.4%00.0%
BP User11350.0%32.7%0.741.0000.0%NANA00.0%NANA
BP Non-user11350.0%43.5%0.163.4010.9%NANA00.0%NANA
Age 21-40700100.0%344.9%71.0%00.0%
BP User34949.9%61.7%0.20<0.00110.3%0.170.1200.0%NANA
BP Non-user35150.1%288.0%0.080.4961.7%0.021.3800.0%NANA
Age 41-502,639100.0%1575.9%321.2%100.4%
BP User1,31950.0%312.4%0.23<0.00180.6%0.330.00510.1%0.110.02
BP Non-user1,32050.0%1269.5%0.150.34241.8%0.150.7490.7%0.010.87
Age 51-6022,101100.0%8563.9%2601.2%700.3%
BP User11,05050.0%1591.4%0.22<0.001470.4%0.22<0.001130.1%0.23<0.001
BP Non-user11,05150.0%6976.3%0.180.262131.9%0.160.30570.5%0.120.42
Age 61-7052,520100.0%1,5943.0%5911.1%1650.3%
BP User26,26050.0%2861.1%0.21<0.0011070.4%0.22<0.001290.1%0.21<0.001
BP Non-user26,26050.0%1,3085.0%0.180.244841.8%0.180.271360.5%0.140.32
Age 71-8038,367100.0%8772.3%5011.3%1720.4%
BP User19,18450.0%1800.9%0.25<0.001850.4%0.20<0.001330.2%0.24<0.001
BP Non-user19,18350.0%6973.6%0.210.304162.2%0.160.251390.7%0.160.35
Age ≥8120,475100.0%4202.1%4362.1%1260.6%
BP User10,23750.0%970.9%0.29<0.001850.8%0.24<0.001270.3%0.27<0.001
BP Non-user10,23850.0%3233.2%0.230.373513.4%0.190.30991.0%0.180.41
Male Patients14,774100.0%5063.4%2711.8%930.6%
BP User7,38950.0%1061.4%0.25<0.001500.7%0.22<0.001180.2%0.24<0.001
BP Non-user7,38550.0%4005.4%0.200.322213.0%0.160.30751.0%0.140.40
By Age
Age ≤20311100.0%82.6%10.3%00.0%
BP User15549.8%31.9%0.600.7200.0%NANA00.0%NANA
BP Non-user15650.2%53.2%0.142.5410.6%NANA00.0%NANA
Age 21-40488100.0%285.7%102.0%10.2%
BP User24450.0%10.4%0.03<0.00110.4%0.110.0200.0%NANA
BP Non-user24450.0%2711.1%0.000.2593.7%0.010.8510.4%NANA
Age 41-50728100.0%273.7%141.9%60.8%
BP User36550.1%51.4%0.22<0.00120.5%0.160.00710.3%0.200.12
BP Non-user36349.9%226.1%0.080.57123.3%0.040.7351.4%0.021.69
Age 51-602,377100.0%954.0%331.4%100.4%
BP User1,18850.0%211.8%0.27<0.00150.4%0.18<0.00120.2%0.250.11
BP Non-user1,18950.0%746.2%0.170.44282.4%0.070.4680.7%0.051.17
Age 61-704,471100.0%1703.8%801.8%240.5%
BP User2,23650.0%361.6%0.26<0.001160.7%0.24<0.00160.3%0.330.01
BP Non-user2,23550.0%1346.0%0.180.37642.9%0.140.42180.8%0.130.84
Age 71-803,786100.0%1323.5%762.0%280.7%
BP User1,89450.0%291.5%0.27<0.001100.5%0.15<0.00140.2%0.16<0.001
BP Non-user1,89250.0%1035.4%0.180.41663.5%0.080.29241.3%0.060.48
Age ≥812,613100.0%461.8%572.2%240.9%
BP User1,30750.0%110.8%0.31<0.001161.2%0.38<0.00150.4%0.260.004
BP Non-user1,30650.0%352.7%0.160.61413.1%0.210.69191.5%0.100.70

  1. BP: bisphosphonate; LL: lower 95% confidence interval level; NA: not applicable; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 9
Unadjusted COVID-19-Related Outcomes Stratified by Age, Sex, & Age by Sex; Matched Primary Analysis Cohort, Region=South.
Region=South Matched
AllSARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
N%N%ORp-valueN%ORp-valueN%ORp-value
LLULLLULLLUL
All Patients319,408100.0%8,4182.6%3,5351.1%8490.3%
BP User159,70450.0%1,5531.0%0.22<0.0016240.4%0.21<0.0011670.1%0.24<0.001
BP Non-user159,70450.0%6,8654.3%0.210.232,9111.8%0.190.236820.4%0.210.29
By Age
Age ≤20943100.0%293.1%40.4%00.0%
BP User47450.3%153.2%1.060.8700.0%NANA00.0%NANA
BP Non-user46949.7%143.0%0.512.2340.9%NANA00.0%NANA
Age 21-402,364100.0%1134.8%251.1%40.2%
BP User1,17749.8%201.7%0.20<0.00140.3%0.19<0.00120.2%1.011.00
BP Non-user1,18750.2%937.8%0.120.33211.8%0.060.5520.2%0.147.17
Age 41-506,839100.0%3294.8%731.1%100.1%
BP User3,42150.0%722.1%0.26<0.001180.5%0.32<0.00150.1%1.000.99
BP Non-user3,41850.0%2577.5%0.200.34551.6%0.190.5550.1%0.293.45
Age 51-6050,186100.0%1,9994.0%5841.2%1030.2%
BP User25,09350.0%3931.6%0.23<0.0011140.5%0.24<0.001230.1%0.29<0.001
BP Non-user25,09350.0%1,6066.4%0.210.264701.9%0.190.29800.3%0.180.46
Age 61-70111,800100.0%3,2462.9%1,1061.0%2470.2%
BP User55,89650.0%5831.0%0.21<0.0011910.3%0.21<0.001380.1%0.18<0.001
BP Non-user55,90450.0%2,6634.8%0.190.239151.6%0.180.242090.4%0.130.26
Age 71-8099,223100.0%1,9422.0%1,0291.0%2600.3%
BP User49,61850.0%3220.6%0.19<0.0011700.3%0.20<0.001550.1%0.27<0.001
BP Non-user49,60550.0%1,6203.3%0.170.228591.7%0.170.232050.4%0.200.36
Age ≥8148,053100.0%7601.6%7141.5%2250.5%
BP User24,02550.0%1480.6%0.24<0.0011270.5%0.21<0.001440.2%0.24<0.001
BP Non-user24,02850.0%6122.5%0.200.285872.4%0.180.261810.8%0.170.34
Female Patients289,263100.0%7,5192.6%3,1591.1%7450.3%
BP User144,63350.0%1,3650.9%0.21<0.0015620.4%0.21<0.0011430.1%0.24<0.001
BP Non-user144,63050.0%6,1544.3%0.200.232,5971.8%0.190.236020.4%0.200.28
By Age
Age ≤20372100.0%113.0%30.8%00.0%
BP User18549.7%63.2%1.220.7500.0%NANA00.0%NANA
BP Non-user18750.3%52.7%0.374.0731.6%NANA00.0%NANA
Age 21-401,543100.0%815.2%161.0%30.2%
BP User77049.9%141.8%0.20<0.00140.5%0.330.0820.3%2.010.62
BP Non-user77350.1%678.7%0.110.35121.6%0.111.0310.1%0.1822.22
Age 41-505,569100.0%2734.9%661.2%90.2%
BP User2,78750.0%652.3%0.30<0.001180.6%0.37<0.00150.2%1.251.00
BP Non-user2,78250.0%2087.5%0.220.39481.7%0.210.6440.1%0.334.65
Age 51-6046,012100.0%1,8194.0%5211.1%890.2%
BP User23,00750.0%3581.6%0.23<0.0011000.4%0.23<0.001160.1%0.22<0.001
BP Non-user23,00550.0%1,4616.4%0.210.264211.8%0.190.29730.3%0.130.38
Age 61-70103,825100.0%2,9482.8%1,0071.0%2180.2%
BP User51,91050.0%5171.0%0.20<0.0011770.3%0.21<0.001330.1%0.18<0.001
BP Non-user51,91550.0%2,4314.7%0.190.238301.6%0.180.251850.4%0.120.26
Age 71-8089,474100.0%1,7291.9%9151.0%2300.3%
BP User44,74250.0%2830.6%0.19<0.0011530.3%0.20<0.001470.1%0.26<0.001
BP Non-user44,73250.0%1,4463.2%0.170.227621.7%0.170.241830.4%0.190.35
Age ≥8142,468100.0%6581.5%6311.5%1960.5%
BP User21,23250.0%1220.6%0.22<0.0011100.5%0.21<0.001400.2%0.26<0.001
BP Non-user21,23650.0%5362.5%0.180.275212.5%0.170.251560.7%0.180.36
Male Patients30,145100.0%8993.0%3761.2%1040.3%
BP User15,07150.0%1881.2%0.26<0.001620.4%0.19<0.001240.2%0.30<0.001
BP Non-user15,07450.0%7114.7%0.220.303142.1%0.150.26800.5%0.190.47
By Age
Age ≤20571100.0%183.2%10.2%00.0%
BP User28950.6%93.1%0.980.9600.0%NANA00.0%NANA
BP Non-user28249.4%93.2%0.382.4910.4%NANA00.0%NANA
Age 21-40821100.0%323.9%91.1%10.1%
BP User40749.6%61.5%0.22<0.00100.0%NANA00.0%NANA
BP Non-user41450.4%266.3%0.090.5592.2%NANA10.2%NANA
Age 41-501,270100.0%564.4%70.6%10.1%
BP User63449.9%71.1%0.13<0.00100.0%NANA00.0%NANA
BP Non-user63650.1%497.7%0.060.3071.1%NANA10.2%NANA
Age 51-604,174100.0%1804.3%631.5%140.3%
BP User2,08650.0%351.7%0.23<0.001140.7%0.28<0.00170.3%1.000.99
BP Non-user2,08850.0%1456.9%0.160.33492.3%0.150.5170.3%0.352.86
Age 61-707,975100.0%2983.7%991.2%290.4%
BP User3,98650.0%661.7%0.27<0.001140.4%0.16<0.00150.1%0.21<0.001
BP Non-user3,98950.0%2325.8%0.210.36852.1%0.090.29240.6%0.080.54
Age 71-809,749100.0%2132.2%1141.2%300.3%
BP User4,87650.0%390.8%0.22<0.001170.3%0.17<0.00180.2%0.360.01
BP Non-user4,87350.0%1743.6%0.150.31972.0%0.100.29220.5%0.160.81
Age ≥815,585100.0%1021.8%831.5%290.5%
BP User2,79350.0%260.9%0.34<0.001170.6%0.25<0.00140.1%0.16<0.001
BP Non-user2,79250.0%762.7%0.210.53662.4%0.150.43250.9%0.060.46

  1. BP: bisphosphonate; LL: lower 95% confidence interval level; NA: not applicable; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 10
Unadjusted COVID-19-Related Outcomes Stratified by Age, Sex, & Age by Sex; Matched Primary Analysis Cohort, Region=West.
Region=West Matched
AllSARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
N%N%ORp-valueN%ORp-valueN%ORp-value
LLULLLULLLUL
All Patients190,534100.0%6,4373.4%2,8351.5%7200.4%
BP User95,26750.0%1,0841.1%0.19<0.0014390.5%0.18<0.0011130.1%0.19<0.001
BP Non-user95,26750.0%5,3535.6%0.180.212,3962.5%0.160.206070.6%0.150.23
By Age
Age ≤20299100.0%93.0%10.3%00.0%
BP User15050.2%10.7%0.120.0200.0%NANA00.0%NANA
BP Non-user14949.8%85.4%0.010.9610.7%NANA00.0%NANA
Age 21-401,115100.0%676.0%181.6%30.3%
BP User55750.0%173.1%0.32<0.00120.4%0.120.00110.2%0.501.00
BP Non-user55850.0%509.0%0.180.56162.9%0.030.5320.4%0.055.53
Age 41-502,806100.0%1475.2%331.2%100.4%
BP User1,40450.0%271.9%0.21<0.00130.2%0.10<0.00110.1%0.110.01
BP Non-user1,40250.0%1208.6%0.140.32302.1%0.030.3290.6%0.010.87
Age 51-6020,761100.0%9524.6%3041.5%540.3%
BP User10,38050.0%1781.7%0.22<0.001530.5%0.21<0.00170.1%0.15<0.001
BP Non-user10,38150.0%7747.5%0.180.262512.4%0.150.28470.5%0.070.33
Age 61-7062,798100.0%2,2283.5%8281.3%1960.3%
BP User31,39250.0%3411.1%0.17<0.0011180.4%0.16<0.001210.1%0.12<0.001
BP Non-user31,40650.0%1,8876.0%0.150.197102.3%0.130.201750.6%0.080.19
Age 71-8064,596100.0%1,9623.0%9151.4%2590.4%
BP User32,30350.0%3361.0%0.20<0.0011370.4%0.17<0.001430.1%0.20<0.001
BP Non-user32,29350.0%1,6265.0%0.180.227782.4%0.140.212160.7%0.140.27
Age ≥8138,159100.0%1,0722.8%7361.9%1980.5%
BP User19,08150.0%1841.0%0.20<0.0011260.7%0.20<0.001400.2%0.25<0.001
BP Non-user19,07850.0%8884.7%0.170.236103.2%0.170.241580.8%0.180.36
Female Patients168,933100.0%5,5753.3%2,4391.4%5760.3%
BP User84,47050.0%9091.1%0.19<0.0013800.4%0.18<0.001920.1%0.19<0.001
BP Non-user84,46350.0%4,6665.5%0.170.202,0592.4%0.160.204840.6%0.150.24
By Age
Age ≤20107100.0%43.7%00.0%00.0%
BP User5450.5%00.0%NANA00.0%NANA00.0%NANA
BP Non-user5349.5%47.5%NANA00.0%NANA00.0%NANA
Age 21-40658100.0%446.7%91.4%20.3%
BP User32950.0%103.0%0.27<0.00110.3%0.120.0400.0%NANA
BP Non-user32950.0%3410.3%0.130.5682.4%0.020.9820.6%NANA
Age 41-502,158100.0%1245.7%211.0%50.2%
BP User1,08050.0%211.9%0.19<0.00120.2%0.10<0.00100.0%NANA
BP Non-user1,07850.0%1039.6%0.120.30191.8%0.020.4550.5%NANA
Age 51-6018,480100.0%8354.5%2641.4%430.2%
BP User9,23950.0%1461.6%0.20<0.001460.5%0.21<0.00140.0%0.10<0.001
BP Non-user9,24150.0%6897.5%0.170.242182.4%0.150.29390.4%0.040.29
Age 61-7057,528100.0%1,9993.5%7271.3%1590.3%
BP User28,76150.0%3001.0%0.17<0.0011110.4%0.18<0.001190.1%0.14<0.001
BP Non-user28,76750.0%1,6995.9%0.150.196162.1%0.140.221400.5%0.080.22
Age 71-8057,396100.0%1,6772.9%7751.4%2080.4%
BP User28,70350.0%2841.0%0.20<0.0011180.4%0.18<0.001360.1%0.21<0.001
BP Non-user28,69350.0%1,3934.9%0.170.226572.3%0.140.211720.6%0.150.30
Age ≥8132,606100.0%8922.7%6432.0%1590.5%
BP User16,30450.0%1480.9%0.19<0.0011020.6%0.18<0.001330.2%0.26<0.001
BP Non-user16,30250.0%7444.6%0.160.235413.3%0.150.231260.8%0.180.38
Male Patients21,601100.0%8624.0%3961.8%1440.7%
BP User10,79750.0%1751.6%0.24<0.001590.5%0.17<0.001210.2%0.17<0.001
BP Non-user10,80450.0%6876.4%0.210.293373.1%0.130.231231.1%0.110.27
By Age
Age ≤20192100.0%52.6%10.5%00.0%
BP User9650.0%11.0%0.240.3700.0%NANA00.0%NANA
BP Non-user9650.0%44.2%0.032.2111.0%NANA00.0%NANA
Age 21-40457100.0%235.0%92.0%10.2%
BP User22849.9%73.1%0.420.0610.4%0.120.0410.4%NANA
BP Non-user22950.1%167.0%0.171.0583.5%0.020.9800.0%NANA
Age 41-50648100.0%233.5%121.9%50.8%
BP User32450.0%61.9%0.340.0210.3%0.090.00610.3%0.250.37
BP Non-user32450.0%175.2%0.130.88113.4%0.010.6941.2%0.032.23
Age 51-602,281100.0%1175.1%401.8%110.5%
BP User1,14150.0%322.8%0.36<0.00170.6%0.21<0.00130.3%0.370.15
BP Non-user1,14050.0%857.5%0.240.54332.9%0.090.4780.7%0.101.41
Age 61-705,270100.0%2294.3%1011.9%370.7%
BP User2,63149.9%411.6%0.21<0.00170.3%0.07<0.00120.1%0.06<0.001
BP Non-user2,63950.1%1887.1%0.150.29943.6%0.030.16351.3%0.010.24
Age 71-807,200100.0%2854.0%1401.9%510.7%
BP User3,60050.0%521.4%0.21<0.001190.5%0.15<0.00170.2%0.16<0.001
BP Non-user3,60050.0%2336.5%0.160.291213.4%0.090.25441.2%0.070.35
Age ≥815,553100.0%1803.2%931.7%390.7%
BP User2,77750.0%361.3%0.24<0.001240.9%0.34<0.00170.3%0.22<0.001
BP Non-user2,77650.0%1445.2%0.170.35692.5%0.210.55321.2%0.100.49

  1. BP: bisphosphonate; LL: lower 95% confidence interval level; NA: not applicable; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 11
Unadjusted COVID-19-Related Outcomes Stratified by Age, Sex, & Age by Sex; Matched Primary Analysis Cohort, Region=New York State.
Region=New York State Matched
AllSARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
N%N%ORp-valueN%ORp-valueN%ORp-value
LLULLLULLLUL
All Patients99,724100.0%3,5983.6%3,6073.6%6220.6%
BP User49,86250.0%7721.5%0.26<0.0018111.6%0.28<0.0011360.3%0.28<0.001
BP Non-user49,86250.0%2,8265.7%0.240.282,7965.6%0.260.304861.0%0.230.34
By Age
Age ≤20102100.0%43.9%22.0%11.0%
BP User5049.0%24.0%1.041.0012.0%1.041.0012.0%NANA
BP Non-user5251.0%23.8%0.147.6911.9%0.0617.1100.0%NANA
Age 21-40453100.0%214.6%153.3%10.2%
BP User22850.3%31.3%0.15<0.00120.9%0.140.00410.4%NANA
BP Non-user22549.7%188.0%0.040.53135.8%0.030.6500.0%NANA
Age 41-501,311100.0%775.9%362.7%40.3%
BP User65550.0%223.4%0.38<0.00181.2%0.28<0.00110.2%0.330.62
BP Non-user65650.0%558.4%0.230.63284.3%0.130.6130.5%0.033.21
Age 51-6012,732100.0%6885.4%5274.1%580.5%
BP User6,36450.0%1552.4%0.27<0.0011181.9%0.28<0.001170.3%0.410.002
BP Non-user6,36850.0%5338.4%0.230.334096.4%0.220.34410.6%0.230.73
Age 61-7032,265100.0%1,2944.0%1,1503.6%1410.4%
BP User16,13650.0%2771.7%0.26<0.0012671.7%0.29<0.001270.2%0.24<0.001
BP Non-user16,12950.0%1,0176.3%0.230.308835.5%0.250.331140.7%0.150.36
Age 71-8034,693100.0%9572.8%1,1963.4%2400.7%
BP User17,34150.0%2041.2%0.26<0.0012571.5%0.26<0.001450.3%0.23<0.001
BP Non-user17,35250.0%7534.3%0.220.319395.4%0.230.301951.1%0.170.32
Age ≥8118,168100.0%5573.1%6813.7%1771.0%
BP User9,08850.0%1091.2%0.23<0.0011581.7%0.29<0.001440.5%0.33<0.001
BP Non-user9,08050.0%4484.9%0.190.295235.8%0.240.351331.5%0.230.46
Female Patients90,567100.0%3,2553.6%3,2353.6%5370.6%
BP User45,28550.0%6871.5%0.26<0.0017261.6%0.28<0.0011080.2%0.25<0.001
BP Non-user45,28250.0%2,5685.7%0.240.282,5095.5%0.260.304290.9%0.200.31
By Age
Age ≤2033100.0%00.0%13.0%13.0%
BP User1648.5%00.0%NANA16.3%NANA16.3%NANA
BP Non-user1751.5%00.0%NANA00.0%NANA00.0%NANA
Age 21-40261100.0%166.1%83.1%10.4%
BP User13250.6%21.5%0.130.00221.5%0.320.1710.8%NANA
BP Non-user12949.4%1410.9%0.030.5764.7%0.061.5900.0%NANA
Age 41-501,032100.0%585.6%282.7%30.3%
BP User51650.0%183.5%0.430.00371.4%0.320.00700.0%NANA
BP Non-user51650.0%407.8%0.240.76214.1%0.140.7730.6%NANA
Age 51-6011,699100.0%6375.4%4824.1%470.4%
BP User5,84950.0%1382.4%0.26<0.0011101.9%0.28<0.001140.2%0.420.006
BP Non-user5,85050.0%4998.5%0.210.313726.4%0.230.35330.6%0.230.79
Age 61-7030,115100.0%1,2044.0%1,0703.6%1260.4%
BP User15,06050.0%2571.7%0.26<0.0012481.6%0.29<0.001230.2%0.22<0.001
BP Non-user15,05550.0%9476.3%0.220.308225.5%0.250.331030.7%0.140.35
Age 71-8031,385100.0%8582.7%1,0523.4%2080.7%
BP User15,68850.0%1761.1%0.25<0.0012211.4%0.26<0.001330.2%0.19<0.001
BP Non-user15,69750.0%6824.3%0.210.308315.3%0.220.301751.1%0.130.27
Age ≥8116,042100.0%4823.0%5943.7%1510.9%
BP User8,02450.0%961.2%0.24<0.0011371.7%0.29<0.001360.4%0.31<0.001
BP Non-user8,01850.0%3864.8%0.190.304575.7%0.240.351151.4%0.210.45
Male Patients9,157100.0%3433.7%3724.1%850.9%
BP User4,57750.0%851.9%0.32<0.001851.9%0.28<0.001280.6%0.490.002
BP Non-user4,58050.0%2585.6%0.250.412876.3%0.220.36571.2%0.310.77
By Age
Age ≤2069100.0%45.8%11.4%00.0%
BP User3449.3%25.9%1.031.0000.0%NANA00.0%NANA
BP Non-user3550.7%25.7%0.147.7712.9%NANA00.0%NANA
Age 21-40192100.0%52.6%73.6%00.0%
BP User9650.0%11.0%0.240.3700.0%NANA00.0%NANA
BP Non-user9650.0%44.2%0.032.2177.3%NANA00.0%NANA
Age 41-50279100.0%196.8%82.9%10.4%
BP User13949.8%42.9%0.250.0210.7%0.140.0710.7%NANA
BP Non-user14050.2%1510.7%0.080.7675.0%0.021.1300.0%NANA
Age 51-601,033100.0%514.9%454.4%111.1%
BP User51549.9%173.3%0.490.0281.6%0.21<0.00130.6%0.370.22
BP Non-user51850.1%346.6%0.270.88377.1%0.090.4481.5%0.101.42
Age 61-702,150100.0%904.2%803.7%150.7%
BP User1,07650.0%201.9%0.27<0.001191.8%0.30<0.00140.4%0.360.08
BP Non-user1,07450.0%706.5%0.160.45615.7%0.180.50111.0%0.111.14
Age 71-803,308100.0%993.0%1444.4%321.0%
BP User1,65350.0%281.7%0.38<0.001362.2%0.32<0.001120.7%0.600.16
BP Non-user1,65550.0%714.3%0.250.601086.5%0.220.47201.2%0.291.23
Age ≥812,126100.0%753.5%874.1%261.2%
BP User1,06450.0%131.2%0.20<0.001212.0%0.30<0.00180.8%0.440.05
BP Non-user1,06250.0%625.8%0.110.37666.2%0.180.50181.7%0.191.02

  1. BP: bisphosphonate; LL: lower 95% confidence interval level; NA: not applicable; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 12
Unadjusted COVID-19-Related Outcomes Stratified by Age, Sex, & Age by Sex; Matched Primary Analysis Cohort, Region=New York State.
SARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.220.210.22<0.0010.220.210.23<0.0010.240.220.26<0.001
Adjusted0.220.210.23<0.0010.230.220.24<0.0010.260.240.29<0.001
NortheastUnadjusted0.220.210.24<0.0010.240.230.26<0.0010.260.230.30<0.001
Adjusted0.230.210.24<0.0010.250.230.26<0.0010.290.260.33<0.001
MidwestUnadjusted0.230.220.25<0.0010.220.200.25<0.0010.230.190.29<0.001
Adjusted0.240.220.26<0.0010.240.220.27<0.0010.260.210.32<0.001
SouthUnadjusted0.220.210.23<0.0010.210.190.23<0.0010.240.210.29<0.001
Adjusted0.220.210.23<0.0010.220.200.24<0.0010.260.230.30<0.001
WestUnadjusted0.190.180.21<0.0010.180.160.20<0.0010.190.150.23<0.001
Adjusted0.200.180.21<0.0010.190.170.21<0.0010.200.160.25<0.001
New YorkUnadjusted0.260.240.28<0.0010.280.260.30<0.0010.280.230.34<0.001
Adjusted0.260.240.28<0.0010.280.260.31<0.0010.330.270.40<0.001

  1. LL: lower 95% confidence interval level; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 13
Statin Use Sensitivity Analysis, Unadjusted/Adjusted Odds Ratio for COVID-19-Related Outcomes, Stratified by Region and New York State.
SARS-CoV-2 TestCOVID-19 DiagnosisCOVID-19 Hospitalization
Statin Uses versus Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.900.890.91<0.0010.910.900.92<0.0011.121.091.15<0.001
Adjusted0.870.860.87<0.0010.790.780.81<0.0010.990.961.020.48
NortheastUnadjusted0.870.850.88<0.0010.880.860.90<0.0011.161.111.21<0.001
Adjusted0.850.840.87<0.0010.770.750.78<0.0011.030.981.070.22
MidwestUnadjusted0.970.950.990.021.101.071.14<0.0011.271.191.36<0.001
Adjusted0.920.900.94<0.0010.990.961.030.751.151.081.23<0.001
SouthUnadjusted0.900.880.91<0.0010.900.880.93<0.0011.000.951.060.90
Adjusted0.850.840.87<0.0010.800.780.83<0.0010.880.830.94<0.001
WestUnadjusted0.880.860.90<0.0010.830.800.86<0.0011.020.951.100.58
Adjusted0.860.830.88<0.0010.710.680.74<0.0010.870.800.94<0.001
New YorkUnadjusted0.910.890.93<0.0010.930.910.96<0.0011.211.141.29<0.001
Adjusted0.920.900.95<0.0010.790.770.82<0.0011.050.981.130.15
BP Users versus BP Non-users among Statin Users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.230.220.24<0.0010.260.250.28<0.0010.260.230.29<0.001
Adjusted0.230.220.24<0.0010.270.250.29<0.0010.280.250.32<0.001
NortheastUnadjusted0.250.230.27<0.0010.290.270.31<0.0010.280.240.34<0.001
Adjusted0.250.230.27<0.0010.290.270.32<0.0010.320.260.38<0.001
MidwestUnadjusted0.240.220.27<0.0010.220.190.25<0.0010.210.160.27<0.001
Adjusted0.250.230.29<0.0010.230.220.25<0.0010.220.170.30<0.001
SouthUnadjusted0.220.210.24<0.0010.260.230.29<0.0010.260.210.33<0.001
Adjusted0.220.200.24<0.0010.270.240.31<0.0010.280.220.36<0.001
WestUnadjusted0.200.180.22<0.0010.220.190.25<0.0010.250.200.33<0.001
Adjusted0.200.180.22<0.0010.230.200.27<0.0010.280.210.36<0.001
New YorkUnadjusted0.270.240.30<0.0010.310.280.35<0.0010.300.230.39<0.001
Adjusted0.280.250.32<0.0010.310.280.35<0.0010.330.250.44<0.001
BP Users versus BP Non-users among Statin Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.230.210.24<0.0010.210.190.23<0.0010.210.170.25<0.001
Adjusted0.240.220.25<0.0010.230.210.25<0.0010.250.210.30<0.001
NortheastUnadjusted0.250.220.27<0.0010.220.200.25<0.0010.240.190.31<0.001
Adjusted0.260.230.29<0.0010.250.220.28<0.0010.290.220.37<0.001
MidwestUnadjusted0.240.210.28<0.0010.220.180.27<0.0010.210.140.31<0.001
Adjusted0.240.200.28<0.0010.250.200.32<0.0010.260.170.39<0.001
SouthUnadjusted0.230.210.25<0.0010.190.150.22<0.0010.180.120.27<0.001
Adjusted0.240.210.27<0.0010.210.170.25<0.0010.220.150.33<0.001
WestUnadjusted0.190.170.22<0.0010.180.150.22<0.0010.160.110.25<0.001
Adjusted0.200.170.23<0.0010.190.180.21<0.0010.180.110.29<0.001
New YorkUnadjusted0.260.230.30<0.0010.260.220.30<0.0010.270.190.39<0.001
Adjusted0.260.220.31<0.0010.250.210.30<0.0010.350.230.52<0.001

  1. LL: lower 95% confidence interval level; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 14
Antihypertensive Use Sensitivity Analysis, Unadjusted/Adjusted Odds Ratio for COVID-19-Related Outcomes, Stratified by Region and New York State.
Odds of SARS-CoV-2 TestOdds of COVID-19 DiagnosisOdds of COVID-19 Hospitalization
Antihypertensive Users versus Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.910.900.92<0.0010.860.850.87<0.0011.131.101.17<0.001
Adjusted0.870.860.88<0.0010.750.740.76<0.0010.980.951.000.10
NortheastUnadjusted0.860.840.87<0.0010.830.820.85<0.0011.201.151.25<0.001
Adjusted0.820.810.83<0.0010.720.710.73<0.0011.040.991.080.10
MidwestUnadjusted1.000.981.020.981.061.031.10<0.0011.281.201.36<0.001
Adjusted0.940.910.96<0.0010.940.900.97<0.0011.111.041.190.002
SouthUnadjusted0.930.920.94<0.0010.880.860.90<0.0011.020.961.070.58
Adjusted0.880.870.89<0.0010.780.760.80<0.0010.890.840.94<0.001
WestUnadjusted0.900.880.92<0.0010.750.730.78<0.0010.990.921.060.83
Adjusted0.870.850.89<0.0010.650.620.67<0.0010.840.780.90<0.001
New YorkUnadjusted0.920.900.94<0.0010.900.870.92<0.0011.231.151.31<0.001
Adjusted0.900.870.92<0.0010.750.730.77<0.0011.010.951.090.70
BP Users versus BP Non-users among Antihypertensive Users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.230.220.24<0.0010.260.250.28<0.0010.260.230.29<0.001
Adjusted0.230.220.24<0.0010.260.250.28<0.0010.270.240.30<0.001
NortheastUnadjusted0.240.220.26<0.0010.280.260.31<0.0010.270.220.32<0.001
Adjusted0.230.210.26<0.0010.280.260.31<0.0010.290.240.34<0.001
MidwestUnadjusted0.260.230.29<0.0010.270.230.31<0.0010.270.210.35<0.001
Adjusted0.270.240.30<0.0010.280.260.30<0.0010.270.200.35<0.001
SouthUnadjusted0.230.210.25<0.0010.240.220.28<0.0010.260.200.32<0.001
Adjusted0.230.210.25<0.0010.240.210.28<0.0010.250.200.32<0.001
WestUnadjusted0.200.180.22<0.0010.210.180.25<0.0010.240.180.31<0.001
Adjusted0.200.180.22<0.0010.220.180.25<0.0010.240.180.33<0.001
New YorkUnadjusted0.260.230.29<0.0010.300.260.33<0.0010.290.220.38<0.001
Adjusted0.250.220.29<0.0010.300.260.34<0.0010.330.240.44<0.001
BP Users versus BP Non-users among Antihypertensive Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.210.200.22<0.0010.200.180.22<0.0010.210.170.25<0.001
Adjusted0.210.200.22<0.0010.220.200.24<0.0010.270.220.32<0.001
NortheastUnadjusted0.210.190.23<0.0010.220.190.24<0.0010.230.180.31<0.001
Adjusted0.220.200.25<0.0010.250.220.28<0.0010.300.220.40<0.001
MidwestUnadjusted0.220.190.25<0.0010.160.120.20<0.0010.200.130.31<0.001
Adjusted0.210.180.25<0.0010.180.140.23<0.0010.260.160.42<0.001
SouthUnadjusted0.200.180.22<0.0010.190.160.22<0.0010.220.150.32<0.001
Adjusted0.200.180.22<0.0010.210.170.25<0.0010.280.190.41<0.001
WestUnadjusted0.190.170.22<0.0010.180.150.22<0.0010.150.090.24<0.001
Adjusted0.200.170.22<0.0010.200.160.25<0.0010.190.110.32<0.001
New YorkUnadjusted0.260.230.31<0.0010.250.210.29<0.0010.230.150.36<0.001
Adjusted0.270.230.32<0.0010.260.220.31<0.0010.260.160.43<0.001

  1. LL: lower 95% confidence interval level; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 15
Antidiabetic Use Sensitivity Analysis, Unadjusted/Adjusted Odds Ratio for COVID-19-Related Outcomes, Stratified by Region and New York State.
Odds of SARS-CoV-2 TestOdds of COVID-19 DiagnosisOdds of COVID-19 Hospitalization
Antidiabetic Users versus Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.980.970.990.011.151.131.18<0.0011.501.451.56<0.001
Adjusted0.920.900.93<0.0010.880.860.90<0.0011.131.081.18<0.001
NortheastUnadjusted1.000.981.020.921.111.091.14<0.0011.551.471.64<0.001
Adjusted0.940.920.97<0.0010.840.810.86<0.0011.181.111.27<0.001
MidwestUnadjusted1.041.011.080.011.391.331.46<0.0011.611.471.76<0.001
Adjusted0.950.910.990.011.111.041.17<0.0011.301.171.44<0.001
SouthUnadjusted0.970.950.990.011.161.121.21<0.0011.391.291.50<0.001
Adjusted0.900.880.93<0.0010.910.870.95<0.0011.040.951.140.40
WestUnadjusted0.910.880.94<0.0011.071.011.120.011.431.301.58<0.001
Adjusted0.860.820.89<0.0010.800.750.85<0.0010.970.861.090.60
New YorkUnadjusted1.061.031.10<0.0011.151.111.19<0.0011.591.461.72<0.001
Adjusted1.061.021.100.0070.870.830.90<0.0011.181.071.300.001
BP Users versus BP Non-users among Antidiabetic Users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.260.240.28<0.0010.290.270.32<0.0010.280.240.33<0.001
Adjusted0.260.240.28<0.0010.290.270.32<0.0010.290.250.34<0.001
NortheastUnadjusted0.280.240.32<0.0010.320.280.35<0.0010.290.230.36<0.001
Adjusted0.280.240.32<0.0010.310.270.35<0.0010.300.240.39<0.001
MidwestUnadjusted0.270.220.33<0.0010.300.240.38<0.0010.280.190.41<0.001
Adjusted0.270.220.34<0.0010.320.260.41<0.0010.290.190.42<0.001
SouthUnadjusted0.290.260.33<0.0010.310.260.36<0.0010.350.260.47<0.001
Adjusted0.300.260.34<0.0010.300.250.36<0.0010.360.260.48<0.001
WestUnadjusted0.190.160.22<0.0010.200.170.25<0.0010.210.150.30<0.001
Adjusted0.190.160.23<0.0010.210.170.26<0.0010.220.150.31<0.001
New YorkUnadjusted0.330.270.40<0.0010.340.290.39<0.0010.350.260.49<0.001
Adjusted0.320.260.40<0.0010.320.280.36<0.0010.400.280.56<0.001
BP Users versus BP Non-users among Antidiabetic Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.240.230.26<0.0010.240.220.26<0.0010.240.200.29<0.001
Adjusted0.250.230.27<0.0010.250.230.28<0.0010.270.220.33<0.001
NortheastUnadjusted0.240.220.28<0.0010.260.220.29<0.0010.250.190.34<0.001
Adjusted0.250.220.29<0.0010.270.240.32<0.0010.280.200.39<0.001
MidwestUnadjusted0.270.220.32<0.0010.220.170.30<0.0010.260.160.42<0.001
Adjusted0.280.240.31<0.0010.230.170.31<0.0010.260.160.45<0.001
SouthUnadjusted0.240.210.27<0.0010.250.200.30<0.0010.290.200.43<0.001
Adjusted0.240.210.27<0.0010.240.210.28<0.0010.330.220.49<0.001
WestUnadjusted0.230.200.27<0.0010.180.140.24<0.0010.130.070.23<0.001
Adjusted0.230.200.28<0.0010.200.150.26<0.0010.150.080.28<0.001
New YorkUnadjusted0.300.250.37<0.0010.300.250.36<0.0010.220.140.36<0.001
Adjusted0.300.250.37<0.0010.310.250.37<0.0010.240.140.41<0.001

  1. LL: lower 95% confidence interval level; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 16
Antidepressant Use Sensitivity Analysis, Unadjusted/Adjusted Odds Ratio for COVID-19-Related Outcomes, Stratified by Region and New York State.
Odds of SARS-CoV-2 TestOdds of COVID-19 DiagnosisOdds of COVID-19 Hospitalization
Antidepressant Users versus Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted1.041.031.05<0.0010.710.700.72<0.0010.810.780.83<0.001
Adjusted1.000.991.010.610.650.640.66<0.0010.750.730.78<0.001
NortheastUnadjusted1.010.991.020.540.710.690.72<0.0010.840.800.88<0.001
Adjusted0.970.950.990.0010.650.630.66<0.0010.770.730.82<0.001
MidwestUnadjusted1.101.081.12<0.0010.750.720.78<0.0010.840.780.90<0.001
Adjusted1.051.031.07<0.0010.690.660.71<0.0010.780.730.84<0.001
SouthUnadjusted1.041.021.05<0.0010.680.660.70<0.0010.740.700.79<0.001
Adjusted0.990.981.010.490.640.620.66<0.0010.720.680.77<0.001
WestUnadjusted1.041.021.060.000.700.670.73<0.0010.770.700.84<0.001
Adjusted0.990.971.020.460.640.610.66<0.0010.700.640.77<0.001
New YorkUnadjusted1.000.971.030.860.770.740.80<0.0010.830.760.91<0.001
Adjusted0.980.951.010.270.720.700.75<0.0010.770.700.85<0.001
BP Users versus BP Non-users among Antidepressant Users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.270.260.28<0.0010.300.280.32<0.0010.310.270.36<0.001
Adjusted0.270.250.28<0.0010.300.280.32<0.0010.330.280.38<0.001
NortheastUnadjusted0.280.260.31<0.0010.330.300.37<0.0010.360.290.45<0.001
Adjusted0.280.250.30<0.0010.320.290.36<0.0010.370.290.47<0.001
MidwestUnadjusted0.300.270.34<0.0010.260.220.31<0.0010.250.180.34<0.001
Adjusted0.300.260.34<0.0010.270.220.33<0.0010.260.180.36<0.001
SouthUnadjusted0.260.240.29<0.0010.270.230.31<0.0010.320.240.41<0.001
Adjusted0.260.240.28<0.0010.270.230.32<0.0010.320.240.43<0.001
WestUnadjusted0.250.220.28<0.0010.270.220.32<0.0010.290.200.41<0.001
Adjusted0.240.210.27<0.0010.290.280.30<0.0010.330.230.48<0.001
New YorkUnadjusted0.300.260.34<0.0010.330.280.38<0.0010.240.160.36<0.001
Adjusted0.300.250.34<0.0010.310.270.37<0.0010.250.160.39<0.001
BP Users versus BP Non-users among Antidepressant Non-users
ORLLULp valueORLLULp valueORLLULp value
AllUnadjusted0.200.190.22<0.0010.220.200.24<0.0010.240.200.28<0.001
Adjusted0.210.190.22<0.0010.230.210.25<0.0010.270.220.32<0.001
NortheastUnadjusted0.210.190.24<0.0010.230.200.26<0.0010.250.190.32<0.001
Adjusted0.220.190.25<0.0010.240.220.25<0.0010.290.220.39<0.001
MidwestUnadjusted0.220.190.26<0.0010.230.180.28<0.0010.280.190.39<0.001
Adjusted0.210.180.25<0.0010.260.240.27<0.0010.320.220.47<0.001
SouthUnadjusted0.200.180.22<0.0010.210.180.25<0.0010.210.150.30<0.001
Adjusted0.200.180.23<0.0010.230.190.27<0.0010.220.160.32<0.001
WestUnadjusted0.180.160.21<0.0010.200.160.25<0.0010.200.130.30<0.001
Adjusted0.190.160.22<0.0010.200.200.21<0.0010.220.140.35<0.001
New YorkUnadjusted0.260.220.32<0.0010.270.230.32<0.0010.290.190.43<0.001
Adjusted0.260.230.30<0.0010.260.220.32<0.0010.350.220.54<0.001

  1. LL: lower 95% confidence interval level; OR: odds ratio; UL: upper 95% confidence interval level.

Appendix 2—table 17
“Bone-Rx” Cohort (All Regions), Patient Characteristics Pre/Post Match.
"Bone-Rx" Cohort / All Observations Unmatched"Bone-Rx" Cohort / All Observations Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients502,895100.0%50,84410.1%452,05189.9%100,996100.0%50,49850.0%50,49850.0%
Age
≤201,1640.2%360.1%1,1280.2%<0.001670.1%360.1%310.1%0.97
21-403,5010.7%4100.8%3,0910.7%7900.8%4030.8%3870.8%
41-509,6311.9%1,0802.1%8,5511.9%2,1072.1%1,0692.1%1,0382.1%
51-6072,13914.3%6,41812.6%65,72114.5%12,77712.7%6,39512.7%6,38212.6%
61-70171,68734.1%14,80929.1%156,87834.7%29,50929.2%14,75129.2%14,75829.2%
71-80157,87731.4%16,15231.8%141,72531.4%32,12931.8%16,05531.8%16,07431.8%
≥8186,89617.3%11,93923.5%74,95716.6%23,61723.4%11,78923.3%11,82823.4%
Gender
Female451,79089.8%44,35487.2%407,43690.1%<0.00188,55287.7%44,23587.6%44,31787.8%0.43
Male51,10510.2%6,49012.8%44,6159.9%12,44412.3%6,26312.4%6,18112.2%
Region
Midwest85,39117.0%9,42418.5%75,96716.8%<0.00118,72018.5%9,36018.5%9,36018.5%1.00
Northeast135,86727.0%16,13931.7%119,72826.5%31,98631.7%15,99331.7%15,99331.7%
South178,11835.4%17,23233.9%160,88635.6%34,28033.9%17,14033.9%17,14033.9%
West103,51920.6%8,04915.8%95,47021.1%16,01015.9%8,00515.9%8,00515.9%
Insurance
Commercial164,15032.6%17,09233.6%147,05832.5%<0.00133,97733.6%16,96333.6%17,01433.7%0.91
Dual33,9696.8%2,5625.0%31,4076.9%5,0565.0%2,5475.0%2,5095.0%
Medicaid84,51416.8%7,03413.8%77,48017.1%13,92513.8%6,98613.8%6,93913.7%
Medicare220,26243.8%24,15647.5%196,10643.4%48,03847.6%24,00247.5%24,03647.6%
PCP Visit 2019
No181,99636.2%18,13035.7%163,86636.2%0.00935,94335.6%17,97935.6%17,96435.6%0.92
Yes320,89963.8%32,71464.3%288,18563.8%65,05364.4%32,51964.4%32,53464.4%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI1.051.911.992.710.951.76<0.0011.932.591.932.601.922.590.76

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 18
“Bone-Rx” Cohort (Region=Northeast), Patient Characteristics Pre/Post Match.
"Bone-Rx" Cohort / Region=Northeast Unmatched"Bone-Rx" Cohort / Region=Northeast Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients135,867100.0%16,13911.9%119,72888.1%31,986100.0%15,99350.0%15,99350.0%
Age
≤202450.2%≤100.1%2360.2%<0.001150.0%≤100.1%≤100.0%0.99
21-408910.7%1270.8%7640.6%2500.8%1240.8%1260.8%
41-502,3401.7%2981.8%2,0421.7%5701.8%2901.8%2801.8%
51-6020,06914.8%2,05912.8%18,01015.0%4,08812.8%2,04912.8%2,03912.7%
61-7045,89633.8%4,80229.8%41,09434.3%9,52629.8%4,76729.8%4,75929.8%
71-8042,82831.5%5,26732.6%37,56131.4%10,46532.7%5,22632.7%5,23932.8%
≥8123,59817.4%3,57722.2%20,02116.7%7,07222.1%3,52822.1%3,54422.2%
Gender
Female122,48590.2%14,11587.5%108,37090.5%<0.00128,15788.0%14,06287.9%14,09588.1%0.57
Male13,3829.8%2,02412.5%11,3589.5%3,82912.0%1,93112.1%1,89811.9%
Insurance
Commercial37,81027.8%4,51728.0%33,29327.8%<0.0018,92727.9%4,45927.9%4,46827.9%0.99
Dual8,4346.2%8295.1%7,6056.4%1,6375.1%8245.2%8135.1%
Medicaid25,29618.6%2,08212.9%23,21419.4%4,12212.9%2,06712.9%2,05512.8%
Medicare64,32747.3%8,71154.0%55,61646.5%17,30054.1%8,64354.0%8,65754.1%
PCP Visit 2019
No56,59341.7%6,72641.7%49,86741.7%0.9513,30741.6%6,65441.6%6,65341.6%0.99
Yes79,27458.3%9,41358.3%69,86158.3%18,67958.4%9,33958.4%9,34058.4%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI1.061.891.972.700.931.71<0.0011.892.571.892.581.892.570.91

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 19
“Bone-Rx” Cohort (Region=Midwest), Patient Characteristics Pre/Post Match.
"Bone-Rx" Cohort / Region=Midwest Unmatched"Bone-Rx" Cohort / Region=Midwest Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients85,391100.0%9,42411.0%75,96789.0%18,720100.0%9,36050.0%9,36050.0%
Age
≤202740.3%≤100.1%2680.4%<0.001130.1%≤100.1%≤100.1%1.00
21-406720.8%790.8%5930.8%1540.8%780.8%760.8%
41-501,8862.2%2022.1%1,6842.2%3892.1%2002.1%1892.0%
51-6013,52215.8%1,28413.6%12,23816.1%2,55913.7%1,28013.7%1,27913.7%
61-7031,25636.6%2,76029.3%28,49637.5%5,51229.4%2,75429.4%2,75829.5%
71-8023,88728.0%2,76629.4%21,12127.8%5,49229.3%2,74829.4%2,74429.3%
≥8113,89416.3%2,32724.7%11,56715.2%4,60124.6%2,29424.5%2,30724.6%
Gender
Female76,69689.8%8,11886.1%68,57890.3%<0.00116,22386.7%8,10286.6%8,12186.8%0.68
Male8,69510.2%1,30613.9%7,3899.7%2,49713.3%1,25813.4%1,23913.2%
Insurance
Commercial34,49440.4%3,36135.7%31,13341.0%<0.0016,69935.8%3,34535.7%3,35435.8%0.96
Dual4,0424.7%4364.6%3,6064.7%8524.6%4294.6%4234.5%
Medicaid8,85610.4%7337.8%8,12310.7%1,4417.7%7297.8%7127.6%
Medicare37,99944.5%4,89451.9%33,10543.6%9,72852.0%4,85751.9%4,87152.0%
PCP Visit 2019
No32,03737.5%3,33035.3%28,70737.8%<0.0016,62835.4%3,31235.4%3,31635.4%0.95
Yes53,35462.5%6,09464.7%47,26062.2%12,09264.6%6,04864.6%6,04464.6%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI1.122.022.122.830.991.86<0.0012.052.722.062.722.052.720.91

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 20
“Bone-Rx” Cohort (Region=South), Patient Characteristics Pre/Post Match.
"Bone-Rx" Cohort / Region=South Unmatched"Bone-Rx" Cohort / Region=South Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients178,118100.0%17,2329.7%160,88690.3%34,280100.0%17,14050.0%17,14050.0%
Age
≤204900.3%160.1%4740.3%<0.001310.1%160.1%150.1%1.00
21-401,3130.7%1360.8%1,1770.7%2620.8%1340.8%1280.7%
41-503,8662.2%4452.6%3,4212.1%8842.6%4442.6%4402.6%
51-6027,38915.4%2,29613.3%25,09315.6%4,57413.3%2,29013.4%2,28413.3%
61-7061,03834.3%5,14229.8%55,89634.7%10,27130.0%5,12929.9%5,14230.0%
71-8056,12631.5%5,52132.0%50,60531.5%10,99032.1%5,49332.0%5,49732.1%
≥8127,89615.7%3,67621.3%24,22015.1%7,26821.2%3,63421.2%3,63421.2%
Gender
Female160,99490.4%15,17988.1%145,81590.6%<0.00130,32288.5%15,14988.4%15,17388.5%0.69
Male17,1249.6%2,05311.9%15,0719.4%3,95811.5%1,99111.6%1,96711.5%
Insurance
Commercial66,33237.2%7,04240.9%59,29036.9%<0.00114,05241.0%7,00740.9%7,04541.1%0.95
Dual14,8298.3%7694.5%14,0608.7%1,5234.4%7694.5%7544.4%
Medicaid23,49213.2%1,84310.7%21,64913.5%3,63910.6%1,82910.7%1,81010.6%
Medicare73,46541.2%7,57844.0%65,88741.0%15,06643.9%7,53544.0%7,53143.9%
PCP Visit 2019
No60,25333.8%5,78533.6%54,46833.9%0.45411,46233.4%5,73633.5%5,72633.4%0.91
Yes117,86566.2%11,44766.4%106,41866.1%22,81866.6%11,40466.5%11,41466.6%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.951.841.862.650.861.70<0.0011.802.541.802.541.792.530.78

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 21
“Bone-Rx” Cohort (Region=West), Patient Characteristics Pre/Post Match.
"Bone-Rx" Cohort / Region=West Unmatched"Bone-Rx" Cohort / Region=West Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients103,519100.0%8,0497.8%95,47092.2%16,010100.0%8,00550.0%8,00550.0%
Age
≤201550.1%≤100.1%1500.2%<0.001≤100.0%≤100.1%≤100.0%0.96
21-406250.6%680.8%5570.6%1240.8%670.8%570.7%
41-501,5391.5%1351.7%1,4041.5%2641.6%1351.7%1291.6%
51-6011,15910.8%7799.7%10,38010.9%1,5569.7%7769.7%7809.7%
61-7033,49732.4%2,10526.2%31,39232.9%4,20026.2%2,10126.2%2,09926.2%
71-8035,03633.8%2,59832.3%32,43834.0%5,18232.4%2,58832.3%2,59432.4%
≥8121,50820.8%2,35929.3%19,14920.1%4,67629.2%2,33329.1%2,34329.3%
Gender
Female91,61588.5%6,94286.2%84,67388.7%<0.00113,85086.5%6,92286.5%6,92886.5%0.89
Male11,90411.5%1,10713.8%10,79711.3%2,16013.5%1,08313.5%1,07713.5%
Insurance
Commercial25,51424.6%2,17227.0%23,34224.4%<0.0014,29926.9%2,15226.9%2,14726.8%1.00
Dual6,6646.4%5286.6%6,1366.4%1,0446.5%5256.6%5196.5%
Medicaid26,87026.0%2,37629.5%24,49425.7%4,72329.5%2,36129.5%2,36229.5%
Medicare44,47143.0%2,97336.9%41,49843.5%5,94437.1%2,96737.1%2,97737.2%
PCP Visit 2019
No33,11332.0%2,28928.4%30,82432.3%<0.0014,54628.4%2,27728.4%2,26928.3%0.89
Yes70,40668.0%5,76071.6%64,64667.7%11,46471.6%5,72871.6%5,73671.7%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI1.171.942.172.671.081.84<0.0012.122.592.122.592.122.590.93

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 22
“Bone-Rx” Cohort (Region=New York State), Patient Characteristics Pre/Post Match.
"Bone-Rx" Cohort / Region=New York State Unmatched"Bone-Rx" Cohort / Region=New York State Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients57,397100.0%7,36212.8%50,03587.2%14,508100.0%7,25450.0%7,25450.0%
Age
≤20560.1%≤100.1%500.1%<0.001110.1%≤100.1%≤100.1%0.96
21-402720.5%440.6%2280.5%760.5%420.6%340.5%
41-507751.4%1201.6%6551.3%2071.4%1071.5%1001.4%
51-607,24912.6%88512.0%6,36412.7%1,74412.0%87112.0%87312.0%
61-7018,43332.1%2,29731.2%16,13632.2%4,54031.3%2,26431.2%2,27631.4%
71-8019,94434.7%2,48233.7%17,46234.9%4,93434.0%2,45533.8%2,47934.2%
≥8110,66818.6%1,52820.8%9,14018.3%2,99620.7%1,50920.8%1,48720.5%
Gender
Female52,04790.7%6,58989.5%45,45890.9%<.00113,10690.3%6,52690.0%6,58090.7%0.13
Male5,3509.3%77310.5%4,5779.1%1,4029.7%72810.0%6749.3%
Insurance
Commercial12,30921.4%1,89425.7%10,41520.8%<0.0013,70625.5%1,85025.5%1,85625.6%1.00
Dual1,7503.0%1542.1%1,5963.2%3072.1%1532.1%1542.1%
Medicaid10,19117.8%1,01613.8%9,17518.3%1,96813.6%98713.6%98113.5%
Medicare33,14757.8%4,29858.4%28,84957.7%8,52758.8%4,26458.8%4,26358.8%
PCP Visit 2019
No21,46237.4%2,78937.9%18,67337.3%0.355,46837.7%2,74437.8%2,72437.6%0.73
Yes35,93562.6%4,57362.1%31,36262.7%9,04062.3%4,51062.2%4,53062.4%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI1.061.841.812.560.951.68<0.0011.692.351.692.361.692.350.98

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 23
“Osteo-Dx-Rx” Cohort, Patient Characteristics Pre/Post Match.
"Osteo-Dx-Rx" Cohort / All Observations Unmatched"Osteo-Dx-Rx" Cohort / All Observations Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients60,043100.0%8,39214.0%51,65186.0%15,898100.0%7,94950.0%7,94950.0%
Age
51-606,44310.7%7539.0%5,69011.0%<0.0011,4309.0%7239.1%7078.9%0.95
61-7020,18733.6%2,49229.7%17,69534.3%4,82130.3%2,39730.2%2,42430.5%
71-8021,54535.9%2,96435.3%18,58136.0%5,67735.7%2,84135.7%2,83635.7%
≥8111,86819.8%2,18326.0%9,68518.8%3,97025.0%1,98825.0%1,98224.9%
State
CA24,48940.8%2,55830.5%21,93142.5%<0.0014,88630.7%2,44330.7%2,44330.7%1.00
FL11,90419.8%1,76721.1%10,13719.6%3,25620.5%1,62820.5%1,62820.5%
IL4,4477.4%6788.1%3,7697.3%1,1687.3%5847.3%5847.3%
NY19,20332.0%3,38940.4%15,81430.6%6,58841.4%3,29441.4%3,29441.4%
Insurance
Commercial12,99021.6%2,04824.4%10,94221.2%<0.0013,73623.5%1,86823.5%1,86823.5%1.00
Dual3,6526.1%3133.7%3,3396.5%5543.5%2773.5%2773.5%
Medicaid13,69822.8%1,78521.3%11,91323.1%3,39221.3%1,69621.3%1,69621.3%
Medicare29,70349.5%4,24650.6%25,45749.3%8,21651.7%4,10851.7%4,10851.7%
PCP Visit 2019
No14,08923.5%2,42728.9%11,66222.6%<0.0014,48728.2%2,24328.2%2,24428.2%0.99
Yes45,95476.5%5,96571.1%39,98977.4%11,41171.8%5,70671.8%5,70571.8%
Cancer Dx
No52,30187.1%6,76580.6%45,53688.2%<0.00113,11682.5%6,54882.4%6,56882.6%0.68
Yes7,74212.9%1,62719.4%6,11511.8%2,78217.5%1,40117.6%1,38117.4%
COPD Dx
No53,44689.0%7,03583.8%46,41189.9%<0.00113,70586.2%6,83486.0%6,87186.4%0.39
Yes6,59711.0%1,35716.2%5,24010.1%2,19313.8%1,11514.0%1,07813.6%
Heart Failure Dx
No56,00593.3%7,49289.3%48,51393.9%<0.00114,47591.0%7,21890.8%7,25791.3%0.28
Yes4,0386.7%90010.7%3,1386.1%1,4239.0%7319.2%6928.7%
Hypertension Dx
No24,96641.6%3,28139.1%21,68542.0%<0.0016,26839.4%3,13739.5%3,13139.4%0.92
Yes35,07758.4%5,11160.9%29,96658.0%9,63060.6%4,81260.5%4,81860.6%
Dyslipidemia Dx
No24,09540.1%3,29539.3%20,80040.3%0.086,18738.9%3,10139.0%3,08638.8%0.81
Yes35,94859.9%5,09760.7%30,85159.7%9,71161.1%4,84861.0%4,86361.2%
Obesity Dx
No53,45389.0%7,58390.4%45,87088.8%<0.00114,46891.0%7,21790.8%7,25191.2%0.35
Yes6,59011.0%8099.6%5,78111.2%1,4309.0%7329.2%6988.8%
Type 2 Diabetes Dx
No44,56574.2%6,13273.1%38,43374.4%0.00911,75974.0%5,85973.7%5,90074.2%0.46
Yes15,47825.8%2,26026.9%13,21825.6%4,13926.0%2,09026.3%2,04925.8%
Depression Dx
No51,60986.0%7,11484.8%44,49586.1%0.00113,69786.2%6,84486.1%6,85386.2%0.84
Yes8,43414.0%1,27815.2%7,15613.9%2,20113.8%1,10513.9%1,09613.8%

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; CA: California; Dx: diagnosis; FL: Florida; IL: Illinois; NY: New York; PCP: primary care physician.

Appendix 2—table 24
Statin Cohort (All Regions), Patient Characteristics Pre/Post Match.
All Observations by Statin Use: UnmatchedAll Observations by Statin Use: Matched
AllStatin Non-usersStatin Usersp-valueAllStatin Non-usersStatin Usersp-value
N%N%N%N%N%N%
All Patients7,906,603100.00%6,403,20881.00%1,503,39519.00%2,872,600100.00%1,436,30050.00%1,436,30050.00%
Age
≤201,840,05023.30%1,838,66528.70%1,3850.10%<0.0012,7720.10%1,3870.10%1,3850.10%0.11
21-401,446,99918.30%1,402,60621.90%44,3933.00%88,7603.10%44,3713.10%44,3893.10%
41-50925,30911.70%789,38512.30%135,9249.00%271,6159.50%135,7489.50%135,8679.50%
51-601,250,19015.80%888,51013.90%361,68024.10%710,48124.70%354,44924.70%356,03224.80%
61-701,181,26114.90%728,70211.40%452,55930.10%857,26929.80%428,32629.80%428,94329.90%
71-80783,7759.90%452,2677.10%331,50822.10%605,36021.10%303,27921.10%302,08121.00%
≥81479,0196.10%303,0734.70%175,94611.70%336,34311.70%168,74011.70%167,60311.70%
Gender
Female4,670,96059.10%3,785,06159.10%885,89958.90%<0.0011,682,35458.60%839,20758.40%843,14758.70%<0.001
Male3,235,64340.90%2,618,14740.90%617,49641.10%1,190,24641.40%597,09341.60%593,15341.30%
Region
Midwest1,467,80218.60%1,188,56918.60%279,23318.60%<0.001542,63818.90%271,31918.90%271,31918.90%1
Northeast2,152,56027.20%1,706,02126.60%446,53929.70%847,86829.50%423,93429.50%423,93429.50%
South3,042,60438.50%2,490,63038.90%551,97436.70%1,046,22436.40%523,11236.40%523,11236.40%
West1,243,63715.70%1,017,98815.90%225,64915.00%435,87015.20%217,93515.20%217,93515.20%
Insurance
Commercial3,938,60349.80%3,350,33252.30%588,27139.10%<0.0011,175,47240.90%587,84740.90%587,62540.90%0.34
Dual156,4972.00%73,5321.10%82,9655.50%110,2073.80%54,8513.80%55,3563.90%
Medicaid2,594,50032.80%2,254,53135.20%339,96922.60%641,34522.30%320,43422.30%320,91122.30%
Medicare1,217,00315.40%724,81311.30%492,19032.70%945,57632.90%473,16832.90%472,40832.90%
PCP Visit 2019
No4,283,69754.20%3,773,78458.90%509,91333.90%<0.0011,016,31335.40%508,58735.40%507,72635.30%0.29
Yes3,622,90645.80%2,629,42441.10%993,48266.10%1,856,28764.60%927,71364.60%928,57464.70%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.621.380.491.231.151.79<0.0011.111.771.121.791.111.75<0.001

  1. CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 25
Statin Cohort (Region=New York State), Patient Characteristics Pre/Post Match.
Region=NY by Statin Use: UnmatchedRegion=NY by Statin Use: Matched
AllStatin Non-usersStatin Usersp-valueAllStatin Non-usersStatin Usersp-value
N%N%N%N%N%N%
All Patients968,296100.0%761,99578.7%206,30121.3%371,072100.0%185,53650.0%185,53650.0%
Age
≤20133,17813.8%133,11117.5%670.0%<0.0011340.0%670.0%670.0%1.00
21-40192,95919.9%188,44624.7%4,5132.2%9,0192.4%4,5082.4%4,5112.4%
41-50127,79413.2%112,34214.7%15,4527.5%30,8608.3%15,4208.3%15,4408.3%
51-60172,44417.8%128,47216.9%43,97221.3%86,13623.2%43,06823.2%43,06823.2%
61-70159,91216.5%100,88413.2%59,02828.6%106,46028.7%53,23328.7%53,22728.7%
71-80120,11712.4%64,5498.5%55,56826.9%91,33724.6%45,67524.6%45,66224.6%
≥8161,8926.4%34,1914.5%27,70113.4%47,12612.7%23,56512.7%23,56112.7%
Gender
Female573,61059.2%454,05059.6%119,56058.0%<0.001215,37558.0%107,42057.9%107,95558.2%0.08
Male394,68640.8%307,94540.4%86,74142.0%155,69742.0%78,11642.1%77,58141.8%
Insurance
Commercial500,91851.7%442,99058.1%57,92828.1%<0.001116,12331.3%58,20631.4%57,91731.2%0.57
Dual6,8140.7%2,4100.3%4,4042.1%4,4471.2%2,1901.2%2,2571.2%
Medicaid252,36626.1%206,10927.0%46,25722.4%83,55022.5%41,70322.5%41,84722.6%
Medicare208,19821.5%110,48614.5%97,71247.4%166,95245.0%83,43745.0%83,51545.0%
PCP Visit 2019
No521,28253.8%446,92958.7%74,35336.0%<0.001146,96739.6%73,67539.7%73,29239.5%0.20
Yes447,01446.2%315,06641.3%131,94864.0%224,10560.4%111,86160.3%112,24460.5%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI0.651.390.511.241.171.77<0.0011.071.731.081.761.061.70<0.001

  1. CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 26
Statin User Cohort (All Regions) by BP Use, Patient Characteristics Pre/Post Match of BP Users/Non-users.
All Statin Users by BP: UnmatchedAll Statin Users by BP: Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients1,436,300100.0%1,218,31984.8%217,98115.2%426,960100.0%213,48050.0%213,48050.0%
Age
≤201,3850.1%1,3650.1%200.0%<0.001420.0%220.0%200.0%1.00
21-4044,3893.1%44,0423.6%3470.2%7040.2%3570.2%3470.2%
41-50135,8679.5%133,85011.0%2,0170.9%4,0330.9%2,0160.9%2,0170.9%
51-60356,03224.8%333,32527.4%22,70710.4%45,43910.6%22,73210.6%22,70710.6%
61-70428,94329.9%356,20829.2%72,73533.4%144,86133.9%72,34133.9%72,52034.0%
71-80302,08121.0%223,65118.4%78,43036.0%150,52735.3%75,31635.3%75,21135.2%
≥81167,60311.7%125,87810.3%41,72519.1%81,35419.1%40,69619.1%40,65819.0%
Gender
Female843,14758.7%646,84653.1%196,30190.1%<0.001383,58689.8%191,78689.8%191,80089.8%0.94
Male593,15341.3%571,47346.9%21,6809.9%43,37410.2%21,69410.2%21,68010.2%
Region
Midwest271,31918.9%237,71819.5%33,60115.4%<0.00167,05015.7%33,52515.7%33,52515.7%1.00
Northeast423,93429.5%366,93630.1%56,99826.1%113,30826.5%56,65426.5%56,65426.5%
South523,11236.4%442,99636.4%80,11636.8%157,83837.0%78,91937.0%78,91937.0%
West217,93515.2%170,66914.0%47,26621.7%88,76420.8%44,38220.8%44,38220.8%
Insurance
Commercial587,62540.9%533,84343.8%53,78224.7%<0.001107,55225.2%53,77425.2%53,77825.2%1.00
Dual55,3563.9%42,0413.5%13,3156.1%24,3805.7%12,1835.7%12,1975.7%
Medicaid320,91122.3%280,79923.0%40,11218.4%76,12117.8%38,05017.8%38,07117.8%
Medicare472,40832.9%361,63629.7%110,77250.8%218,90751.3%109,47351.3%109,43451.3%
PCP Visit 2019
No507,72635.3%430,44635.3%77,28035.5%0.27151,39535.5%75,61435.4%75,78135.5%0.59
Yes928,57464.7%787,87364.7%140,70164.5%275,56564.5%137,86664.6%137,69964.5%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI1.111.751.131.770.951.66<0.0010.971.660.971.660.971.670.79

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 27
Statin User Cohort (Region=New York State) by BP Use, Patient Characteristics Pre/Post Match of BP Users/Non-users.
Region=NY Statin Users by BP: UnmatchedRegion=NY Statin Users by BP: Matched
AllBP Non-userBP Userp-valueAllBP Non-userBP Userp-value
N%N%N%N%N%N%
All Patients185,536100.0%161,67387.1%23,86312.9%47,472100.0%23,73650.0%23,73650.0%
Age
≤20670.0%670.0%00.0%<0.001520.1%260.1%260.1%1.00
21-404,5112.4%4,4852.8%260.1%3040.6%1520.6%1520.6%
41-5015,4408.3%15,2889.5%1520.6%4,3819.2%2,1929.2%2,1899.2%
51-6043,06823.2%40,87925.3%2,1899.2%14,71731.0%7,35831.0%7,35931.0%
61-7053,22728.7%45,86128.4%7,36630.9%18,18938.3%9,09238.3%9,09738.3%
71-8045,66224.6%36,47422.6%9,18838.5%9,82920.7%4,91620.7%4,91320.7%
≥8123,56112.7%18,61911.5%4,94220.7%00.0%0.0%0.0%
Gender
Female107,95558.2%86,19453.3%21,76191.2%<0.00143,26591.1%21,63191.1%21,63491.1%0.96
Male77,58141.8%75,47946.7%2,1028.8%4,2078.9%2,1058.9%2,1028.9%
Insurance
Commercial57,91731.2%54,41133.7%3,50614.7%<0.0017,00814.8%3,50214.8%3,50614.8%1.00
Dual2,2571.2%1,6641.0%5932.5%1,1282.4%5642.4%5642.4%
Medicaid41,84722.6%37,92623.5%3,92116.4%7,64416.1%3,82116.1%3,82316.1%
Medicare83,51545.0%67,67241.9%15,84366.4%31,69266.8%15,84966.8%15,84366.7%
PCP Visit 2019
No73,29239.5%63,79739.5%9,49539.8%0.3318,87039.7%9,43439.7%9,43639.8%0.99
Yes112,24460.5%97,87660.5%14,36860.2%28,60260.3%14,30260.3%14,30060.2%
Continuous Outcomes
meanSDmeanSDmeanSDp-valuemeanSDmeanSDmeanSDp-value
CCI1.061.701.081.710.921.59<0.0010.921.580.921.570.931.590.64

  1. BP: bisphosphonate; CCI: Charlson Comorbidity Index; PCP: primary care physician; SD: standard deviation.

Appendix 2—table 28
Statin Non-user Cohort (All Regions) by BP Use, Patient Characteristics Pre/Post Match of BP Users/Non-users.
All Statin Non-users by BP Use: UnmatchedAll Statin Non-users by BP: Matched
AllBP Non-usersBP Usersp-valueAllBP Non-usersBP Usersp-value
N%N%N%N%N%N%
All Patients1,436,300100.0%1,311,45791.3%124,8438.7%249,432100.0%124,71650.0%124,71650.0%
Age
≤201,3870.1%1,3830.1%40.0%<0.00160.0%20.0%40.0%0.99
21-4044,3713.1%44,1703.4%2010.2%4130.2%2120.2%2010.2%
41-50135,7489.5%134,30510.2%1,4431.2%2,8801.2%1,4371.2%1,4431.2%
51-60354,44924.7%336,77925.7%17,67014.2%35,33514.2%17,66514.2%17,67014.2%
61-70428,32629.8%381,93629.1%46,39037.2%92,79137.2%46,40137.2%46,39037.2%
71-80303,27921.1%264,15720.1%39,12231.3%78,07731.3%39,03731.3%39,04031.3%
≥81168,74011.7%148,72711.3%20,01316.0%39,93016.0%19,96216.0%19,96816.0%
Gender
Female839,20758.4%727,32455.5%111,88389.6%<0.001223,50189.6%111,74589.6%111,75689.6%0.94
Male597,09341.6%584,13344.5%12,96010.4%25,93110.4%12,97110.4%12,96010.4%
Region
Midwest271,31918.9%249,38319.0%21,93617.6%<0.00143,87017.6%21,93517.6%21,93517.6%1.00
Northeast423,93429.5%390,13429.7%33,80027.1%67,59427.1%33,79727.1%33,79727.1%
South523,11236.4%480,68036.7%42,43234.0%84,61833.9%42,30933.9%42,30933.9%
West217,93515.2%191,26014.6%26,67521.4%53,35021.4%26,67521.4%26,67521.4%
Insurance
Commercial587,84740.9%552,48742.1%35,36028.3%<0.00170,72528.4%35,36528.4%35,36028.4%1.00
Dual54,8513.8%46,3713.5%8,4806.8%16,6966.7%8,3426.7%8,3546.7%
Medicaid320,43422.3%