1. Subjects Randomized to Denosumab or Bisphosphonate Therapy
Appendix Figure 1: Funnel Plot of Three Studies Comparing Change in Spine Bone Mineral Density Between
Subjects Randomized to Denosumab or Bisphosphonate Therapy

2. Between Subjects Randomized to Denosumab versus Bisphosphonate
Appendix Figure 2: Funnel Plot of Studies Comparing the Percent Change in Total Hip Bone Mineral Density
Between Subjects Randomized to Denosumab versus Bisphosphonate

3. Between Subjects Randomized to Denosomab versus Bisphosphonate
Appendix Figure 3. Funnel Plot of Studies Comparing the Percent Change in Femoral Neck Bone Mineral Density
Between Subjects Randomized to Denosomab versus Bisphosphonate

4. Randomization to Denosumab or Bisphosphonate Therapy
Appendix Figure 4: Funnel Plot of Studies Describing Relative Risk of Fractures by
Randomization to Denosumab or Bisphosphonate Therapy

5. Bisphosphonate in Studies of Glucocorticoid Induced Osteoporosis
Appendix Figure 5. Funnel Plot of Studies Comparing Risk of Infections between Denosumab vs.
Bisphosphonate in Studies of Glucocorticoid Induced Osteoporosis

6. Relative Risk of Adverse Events by Treatment Assignment RR
Study
Random effects
Heterogeneity: I 2
= 83% , t = p
< 0.01
Mok, 2015
Iseri, 2018
Saag, 2018
Events 18 4
285
Total
429 21 14
394
Denosumab 5
265
419
384
Bisphosphonate
0.01
0.1 1 10
100
Risk Ratio
Relative Risk of Adverse Events by Treatment Assignment RR
2.23
3.60
9.00
1.05
95% CI
[0.70; ]
[1.64; ]
[0.53; ]
[0.96; ]
100.0%
39.5%
12.4%
48.1%
Weight
Appendix Figure 6: Relative Risk of Adverse Events by Treatment Assignment

7. Appendix Figure 7: Funnel Plot of Three Studies Comparing Adverse Events of Denosumab vs.
Bisphosphonate Therapy in Studies of Glucocorticoid Induced Osteoporosis

8. Relative Risk of Serious Adverse Events by Treatment Assignment RR
Appendix Figure 8: Relative Risk of Serious Adverse Events by Treatment Assignment
Study
Random effects
Heterogeneity: I 2
= 18% , t = p
= 0.27
Mok, 2015
Iseri, 2018
Saag, 2018
Events 63
Total
429 21 14
394
Denosumab 65
419
384
Bisphosphonate
0.1
0.5 1 10
Risk Ratio
Relative Risk of Serious Adverse Events by Treatment Assignment RR
1.11
5.00
0.94
95% CI
[0.42; 2.93]
[0.26; 95.32]
[0.69; 1.30]
100.0%
0.0%
9.7%
90.3%
Weight

9. vs Bisphosphonate for Glucocorticoid Induced Osteoporosis
Appendix Figure 9: Funnel Plot of Studies Reporting Serious Adverse Events of Denosumab
vs Bisphosphonate for Glucocorticoid Induced Osteoporosis

10. Percent Change in Spine BMD MD 95%-CI Weight
Appendix Figure 10: Percent Change in Spine Bone Mineral Density between Subjects Randomized to Denosumab or Control
Denosumab
Control
Study
Total
Mean SD
Total
Mean SD
Percent Change in Spine BMD MD
95%-CI
Weight
Mok 2015 20
3.39
4.02 20
1.48
1.79
1.91
[-0.02; 3.84]
8.7%
Iseri 2018 14
5.30
3.74 14
2.00
4.49
3.30
[ 0.24; 6.36]
3.4%
Saag, 2018 starting GC
118
3.70
4.00
126
0.90
3.90
2.80
[ 1.81; 3.79]
32.8%
Saag, 2018 continuing GC
209
4.30
4.00
210
2.30
4.50
2.00
[ 1.18; 2.82]
48.6%
Dore* 2010 21
3.50
2.90 15
0.40
3.70
3.10
[ 0.85; 5.35]
6.4%
382
385
Random effects
2.37
[ 1.80; 2.94]
100.0%
Heterogeneity: I 2
= 0% , t 2
= 0 , p
= 0.65 -6 -4 -2 2 4 6
*The Dore study used a placebo control;
all other studies used bisphosphonate as the control
←Favors Bisphosphonate Favors Denosumab→

11. Bone Mineral Density between Denosumab and Control
Appendix Figure 11: Funnel Plot of Four Studies Comparing Percent Change in Spine
Bone Mineral Density between Denosumab and Control

12. Percent Change in Total Hip Bone Mineral Density
Study
Random effects
Heterogeneity: I 2
= 25% , t = p
= 0.26
Mok 2015
Saag 2018, GC starting
Saag 2018, GC continuing
Dore* 2010
Total
364 20
115
208 21
Mean
1.38
1.70
2.20
1.60 SD
2.683
2.700
2.900
1.900
Denosumab
368
125 15
0.8
0.1
0.6
-1.2
2.24
2.60
3.10
Control -4 -2 4
Percent Change in Total Hip Bone Mineral Density
Appendix Figure 12: Percent Change in Total Hip Bone Mineral Density in Subjects Randomized to Denosumab versus Control
←Favors Bisphosphonate Favors Denosumab→ MD
1.62
0.58
2.80
95%-CI
[ 1.10; 2.13]
[-0.95; 2.11]
[ 0.93; 2.27]
[ 1.02; 2.18]
[ 1.25; 4.35]
100.0%
10.1%
36.4%
43.6%
9.9%
Weight
*The Dore study used a placebo control;
all other studies used bisphosphonate as the control

13. in Subjects Randomized to Denosumab versus Control
Appendix Figure 13: Funnel Plot of Studies Comparing the Percent Change in Total Hip Bone Mineral Density
in Subjects Randomized to Denosumab versus Control

14. Relative Risk of Fractures by Treatment Assignment RR
Study
Random effects
Heterogeneity: I 2
= 0%
, t ?
= 0 , p
= 0.54
Mok 2015
Iseri 2018
Saag 2018
Dore* 2010
Events 1 26
Total
504 21 14
398 71
Denosumab 23
507
397 75
Control
0.1
0.5 10
Risk Ratio
Relative Risk of Fractures by Treatment Assignment RR
1.16
3.00
1.13
95%-CI
[0.68; 1.98]
[0.13; 67.72]
[0.65; 1.94]
100.0%
0.0%
3.0%
97.0%
Weight
Appendix Figure 14: Relative Risk of Fractures by Treatment with Bisphosphonate versus Control
*The Dore study used a placebo control;
all other studies used bisphosphonate as the control

15. with Bisphosphonate versus Control
Appendix Figure 15: Funnel Plots of Studies Reporting the Relative Risk of Fractures by Treatment
with Bisphosphonate versus Control

16. Relative Risk of Infection by Treatment Assignment RR
Study
Random effects
Heterogeneity: I 2
= 35% , t = p
= 0.21
Mok 2015
Iseri 2018
Saag^ 2018
Dore* 2010
Events 7 17 29
Total
500 21 14
394 71
Denosumab 1 15 27
494
384 75
Other
0.1
0.5 10
Risk Ratio
Relative Risk of Infection by
Treatment Assignment RR
1.26
7.00
1.10
1.13
95% CI
[0.75; 2.13]
[0.94; 52.04]
[0.56; 2.18]
[0.75; 1.71]
100.0%
6.4%
0.0%
35.8%
57.8%
Weight
Appendix Figure 16: Relative Risk of Infection by Treatment Assignment
*The Dore study used a placebo control;
all other studies used bisphosphonate as the control

17. Bisphosphonate or Placebo in Glucocorticoid Induced Osteoporosis
Appendix Figure 17: Funnel Plot of Infections in Studies Comparing Denosumab vs.
Bisphosphonate or Placebo in Glucocorticoid Induced Osteoporosis

18. Relative Risk of Adverse Events by Treatment Assignment RR
Study
Random effects
Heterogeneity: I 2
= 78% , t = p
< 0.01
Mok, 2015
Iseri, 2018
Saag, 2018
Dore,* 2010
Events 18 4
285 60
Total
500 21 14
394 71
Denosumab 5
265 67
494
384 75
Other
0.01
0.1 1 10
100
Risk Ratio
Relative Risk of Adverse Events by Treatment Assignment RR
1.13
3.60
9.00
1.05
0.95
95% CI
[0.88; ]
[1.64; ]
[0.53; ]
[0.96; ]
[0.83; ]
100.0%
8.5%
0.8%
46.6%
44.1%
Weight
Appendix Figure 18: Relative Risk of Adverse Events by Treatment Assignment
*The Dore study used a placebo control;
all other studies used bisphosphonate as the control

19. Appendix Figure 19: Funnel Plot of Studies Comparing Adverse Events of Denosumab vs.
Bisphosphonate or Placebo in Studies of Glucocorticoid Induced Osteoporosis

20. Relative Risk of Serious Adverse Events by Treatment Assignment RR
Study
Random effects
Heterogeneity: I 2
= 17% , t
= 0.082 p
= 0.30
Mok, 2015
Iseri, 2018
Saag, 2018
Dore,* 2010
Events 63 3
Total
500 21 14
394 71
Denosumab 65 7
494
384 75
Other
0.1
0.5 1 10
Risk Ratio
Relative Risk of Serious Adverse Events by Treatment
Assignment RR
0.89
5.00
0.94
0.45
95% CI
[0.50; 1.59]
[0.26; 95.32]
[0.69; 1.30]
[0.12; 1.68]
100.0%
0.0%
3.7%
80.0%
16.3%
Weight
Appendix Figure 20: Relative Risk of Serious Adverse Events by Treatment Assignment; Denosumab vs Bisphosphonate or Placebo
*The Dore study used a placebo control;
all other studies used bisphosphonate as the control

21. Appendix Figure 21: Funnel Plot of Studies Comparing Serious Adverse Events of Denosumab vs.
Bisphosphonate or Placebo in Studies of Glucocorticoid Induced Osteoporosis