1. CaD TrialObservational Study All participantsNo Personal Supplements a Non-users ofCalcium +CalciumVitamin D PlaceboCaDPlaceboCaDSupplementsVitamin DOnly Number of women 18,10618,1767584771823,56115,47659411914 HIP FRACTURE Cases 19917580682121585526 Age-adjusted incidence (%) b 0.200.170.200.160.140.150.130.18 TOTAL FRACTURE Cases 2158210287087231722344834290 Age-adjusted incidence (%) b 1.941.851.861.812.022.282.042.21 MYOCARDIAL INFARCTION Cases 3904111671934332107740 Age-adjusted incidence (%) b 0.340.37 0.420.280.190.180.29 CORONARY HEART DISEASE Cases 4754992112295452529550 Age-adjusted incidence (%) b 0.420.450.470.510.350.230.220.36 TOTAL HEART DISEASE Cases 136314056426211602762328132 Age-adjusted incidence (%) b 1.241.281.441.391.050.710.770.97 STROKE Cases 3773621621844712539138 Age-adjusted incidence (%) b 0.350.330.370.420.310.230.210.27 Age-adjusted annualized incidence rates in the WHI CaD trial and Observational Study

2. CaD TrialObservational Study All participants No Personal Supplements a Non-users ofCalcium +CalciumVitamin D PlaceboCaDPlaceboCaDSupplementsVitamin DOnly TOTAL CARDIOVASCULAR DISEASE Cases 1810183281384821871069440181 Age-adjusted incidence (%) b 1.691.701.861.941.451.011.041.34 COLORECTAL CANCER Cases 1541687766174 88359 Age-adjusted incidence (%) b 0.130.150.160.140.110.08 0.06 BREAST CANCER Cases 54652824920266551721060 Age-adjusted incidence (%) b 0.450.430.480.380.400.480.490.43 TOTAL INVASIVE CANCER Cases 1411136661755317011187474153 Age-adjusted incidence (%) b 1.211.161.281.111.071.111.12 DEATH Cases 8077443383311240674266119 Age-adjusted incidence (%) b 0.720.670.750.720.780.61 0.84 Age-adjusted annualized incidence rates in the WHI CaD trial and Observational Study (continued)

3. CaD TrialObservationalCombined Trial and OS Years since CaD initiation All ParticipantsNo Personal Supplements a StudyAll ParticipantsNo Personal Supplements a HR95% CIHR95% CIHR95% CIHR95% CIHR95% CI HIP FRACTURE < 20.750.44,1.261.120.52,2.421.410.44,4.570.810.49,1.311.150.58,2.30 2 - 51.010.73,1.401.000.61,1.651.220.71,2.101.030.77,1.391.040.68,1.57 > 50.820.61,1.120.620.38,1.000.840.66,1.070.780.59,1.030.650.44,0.98 Trend test b 0.96 0.13 0.14 0.43 0.02 HR in OS/HR in Trial c 1.090.78,1.541.280.82,1.98 Overall HR d 0.880.71, 1.080.860.62, 1.200.880.70, 1.11 TOTAL FRACTURE < 20.960.86,1.080.910.76,1.100.890.61,1.310.950.85,1.060.900.76,1.06 2 - 50.940.86,1.030.970.84,1.121.050.91,1.220.950.87,1.030.980.87,1.11 > 50.980.88,1.091.030.87,1.221.081.01,1.140.980.90,1.081.020.90,1.16 Trend test b 0.83 0.35 0.42 0.53 0.21 HR in OS/HR in Trial c 1.090.99,1.211.050.92,1.20 Overall HR d 0.960.90, 1.020.970.88, 1.071.071.01, 1.14 DEATH < 20.730.56,0.960.680.44,1.061.490.79,2.830.800.62,1.040.860.58,1.27 2 - 50.870.75,1.020.870.68,1.110.850.61,1.180.870.76,1.010.890.72,1.09 > 51.010.87,1.181.120.89,1.400.950.85,1.060.990.86,1.131.040.86,1.26 Trend test b 0.03 0.71 0.09 0.17 HR in OS/HR in Trial c 0.970.82,1.150.920.74,1.14 Overall HR d 0.910.83, 1.010.950.81, 1.110.950.85, 1.06 Hazard ratios and 95% confidence intervals for calcium plus vitamin D supplementation from the WHI CaD trial and the Observational Study according to years from supplement initiation: Fractures and Total Deaths

4. CaD TrialObservationalCombined Trial and OS Years since CaD initiation All ParticipantsNo Personal Supplements a StudyAll ParticipantsNo Personal Supplements a HR95% CIHR95% CIHR95% CIHR95% CIHR95% CI MYOCARDIAL INFARCTION < 21.190.89,1.591.300.86,1.970.560.14,2.271.150.87,1.511.210.82,1.78 2 - 50.970.78,1.211.040.74,1.471.040.66,1.631.000.82,1.231.110.82,1.49 > 51.010.80,1.291.060.74,1.500.890.73,1.081.000.80,1.241.050.78,1.41 Trend test b 0.46 0.49 0.94 0.49 0.54 HR in OS/HR in Trial c 0.900.69,1.180.850.61,1.18 Overall HR d 1.030.90, 1.191.110.90, 1.370.900.75, 1.09 CORONARY HEART DISEASE e < 21.100.85,1.431.020.69,1.490.490.12,2.001.070.83,1.380.970.67,1.38 2 - 50.960.79,1.181.060.78,1.451.000.66,1.631.000.83,1.201.100.84,1.44 > 51.050.85,1.301.020.75,1.400.880.74,1.051.030.85,1.251.020.78,1.33 Trend test b 0.87 0.97 0.88 0.93 HR in OS/HR in Trial c 0.860.67,1.100.860.64,1.16 Overall HR d 1.030.90, 1.171.030.85, 1.250.880.74, 1.04 TOTAL HEART DISEASE f < 21.050.90,1.211.000.80,1.240.860.50,1.461.040.90,1.200.990.81,1.21 2 - 51.000.89,1.121.050.88,1.260.930.73,1.171.020.91,1.131.050.90,1.23 > 51.040.91,1.190.980.81,1.200.870.79,0.971.020.91,1.150.990.84,1.16 Trend test b 0.96 0.91 0.83 0.88 0.91 HR in OS/HR in Trial c 0.860.75,0.990.820.74,1.05 Overall HR d 1.020.95, 1.111.020.91, 1.140.870.79, 0.96 Hazard ratios and 95% confidence intervals for calcium plus vitamin D supplementation from the WHI CaD trial and Observational Study according to years from supplement initiation: Cardiovascular Diseases

5. CaD TrialObservationalCombined Trial and OS Years since CaD initiation All ParticipantsNo Personal Supplements a StudyAll ParticipantsNo Personal Supplements a HR95% CIHR95% CIHR95% CIHR95% CIHR95% CI STROKE < 20.820.60,1.121.110.73,1.680.470.12,1.890.780.58,1.051.000.68,1.46 2 – 51.060.84,1.341.170.83,1.650.910.57,1.441.030.84,1.271.160.87,1.55 > 50.920.73,1.171.090.79,1.520.930.77,1.110.980.80.1.201.170.90,1.54 Trend test b 0.71 0.93 0.43 0.37 0.53 HR in OS/HR in Trial c 0.960.75,1.230.810.60,1.09 Overall HR d 0.950.82,1.101.120.90,1.390.920.77,1.09 TOTAL CARDIOVASCULAR DISEASE < 20.970.85,1.111.020.84,1.230.870.55,1.350.970.86,1.101.020.85,1.21 2 - 50.990.89,1.101.030.89,1.210.910.74,1.111.010.92,1.101.040.91,1.19 > 51.050.93,1.181.020.86,1.210.860.79,0.941.020.93,1.131.010.88,1.16 Trend test b 0.37 0.97 0.84 0.42 0.93 HR in OS/HR in Trial c 0.850.75,0.960.850.73,0.99 Overall HR d 1.000.94,1.071.030.93,1.130.860.79,0.94 Hazard ratios and 95% confidence intervals for calcium plus vitamin D supplementation from the WHI CaD trial and Observational Study according to years from supplement initiation: Cardiovascular Diseases (continued)

6. CaD TrialObservationalCombined Trial and OS Years since CaD initiation All ParticipantsNo Personal Supplements a StudyAll ParticipantsNo Personal Supplements a HR95% CIHR95% CIHR95% CIHR95% CIHR95% CI COLORECTAL CANCER < 20.890.57,1.380.710.35,1.440.940.23,3.870.920.60,1.400.750.39,1.45 2 - 51.000.71,1.410.750.45,1.240.800.39,1.651.020.74,1.410.780.50,1.21 > 51.300.88,1.920.990.56,1.770.830.60,1.141.230.87,1.740.900.56,1.45 Trend test b 0.19 0.44 0.96 0.26 0.57 HR in OS/HR in Trial d 0.690.45,1.070.940.55,1.59 Overall HR d 1.060.85, 1.320.810.58, 1.130.830.61, 1.12 BREAST CANCER < 21.000.79,1.270.980.68,1.420.900.44,1.830.970.78,1.220.880.64,1.22 2 - 50.980.82,1.180.750.56,1.001.050.78,1.410.950.81,1.120.750.59,0.95 > 50.890.72,1.110.730.52,1.021.141.00,1.300.950.80,1.140.800.62,1.02 Trend test b 0.45 0.26 0.42 0.89 0.87 HR in OS/HR in Trial c 1.180.96,1.451.421.09,1.84 Overall HR d 0.960.85, 1.080.800.66, 0.961.120.99, 1.28 TOTAL INVASIVE CANCER < 20.960.83,1.120.960.76,1.220.870.56,1.360.950.82,1.090.910.74,1.12 2 - 50.940.84,1.060.820.69,0.980.990.82,1.200.940.85.1.050.840.73,0.97 > 50.990.87,1.130.890.73,1.091.040.95,1.130.990.89,1.110.900.77,1.05 Trend test b 0.77 0.73 0.31 0.48 0.72 HR in OS/HR in Trial d 1.040.91,1.181.150.97,1.35 Overall HR d 0.960.89, 1.040.880.78, 0.981.030.95, 1.11 Hazard ratios and 95% confidence intervals for calcium plus vitamin D supplementation from the WHI CaD trial and Observational Study according to years from supplement initiation: Invasive Cancer

7. Duration of CaD Supplementation All ParticipantsNo Personal SupplementsAll ParticipantsNo Personal Supplements HR95% CIHR95% CIHR95% CIHR95% CI HIP FRACTURETOTAL FRACTURE < 20.620.33,1.150.880.32,2.430.950.83,1.080.870.70,1.06 2 - 50.830.50,1.370.660.28,1.520.900.79,1.030.910.73,1.13 > 50.730.44,1.230.240.07,0.840.980.82,1.160.950.71,1.27 Trend test a 0.740.120.890.61 Overall HR b 0.730.54, 1.000.550.32, 0.970.940.86, 1.020.900.78, 1.03 MYOCARDIAL INFARCTIONCORONARY HEART DISEASE < 21.230.90,1.691.370.86,2.181.210.90,1.621.140.74,1.76 2 - 51.070.78,1.491.350.81,2.261.010.74,1.361.260.78,2.01 > 50.820.55,1.210.780.43,1.410.880.61,1.260.820.47,1.41 Trend test a 0.120.17 0.40 Overall HR b 1.060.87, 1.291.180.88, 1.591.040.87, 1.251.080.82, 1.42 TOTAL HEART DISEASESTROKE < 21.060.89,1.251.050.82,1.34 0.810.57,1.141.010.63,1.64 2 - 51.010.85,1.191.000.77,1.31 1.190.85,1.671.730.99,3.01 > 51.040.84,1.300.920.66,1.290.880.57,1.360.920.48,1.76 Trend test a 0.870.560.600.96 Overall HR b 1.030.93, 1.151.000.86, 1.180.960.78, 1.191.180.86, 1.62 Hazard ratios and 95% confidence intervals for calcium and vitamin D supplementation in the WHI CaD trial according to duration of supplementation among women adherent to their assigned study pills

8. Duration of CaD Supplementation All ParticipantsNo Personal SupplementsAll ParticipantsNo Personal Supplements HR95% CIHR95% CIHR95% CIHR95% CI TOTAL CARDIOVASCULAR DISEASECOLORECTAL CANCER < 20.980.85,1.141.040.84,1.290.910.56,1.470.730.34,1.60 2 – 51.040.89,1.201.070.84,1.341.010.62,1.660.920.44,1.93 > 51.060.88,1.290.980.73,1.311.100.59,2.070.710.27,1.88 Trend test a 0.490.770.630.98 Overall HR b 1.020.93, 1.121.040.90, 1.190.990.73, 1.340.800.50, 1.27 BREAST CANCERTOTAL INVASIVE CANCER < 20.960.73,1.270.900.58,1.390.970.82,1.140.940.71,1.23 2 - 50.850.66,1.100.600.39,0.920.860.74,1.020.700.53,0.92 > 50.880.63,1.240.670.39,1.170.950.77,1.180.790.56,1.11 Trend test a 0.640.350.810.35 Overall HR b 0.900.76, 1.060.710.55, 0.930.920.83, 1.020.800.68, 0.95 DEATH < 20.780.57,1.080.690.41,1.16 2 - 50.810.63,1.040.820.54,1.26 > 51.060.80,1.411.020.65,1.59 Trend test a 0.140.26 Overall HR b 0.880.75, 1.030.850.65, 1.11 Hazard ratios and 95% confidence intervals for calcium and vitamin D supplementation in the WHI CaD trial according to duration of supplementation among women adherent to their assigned study pills (continued)