CaD TrialObservational Study All participantsNo Personal Supplements a Non-users ofCalcium +CalciumVitamin D PlaceboCaDPlaceboCaDSupplementsVitamin DOnly.

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CaD TrialObservational Study All participantsNo Personal Supplements a Non-users ofCalcium +CalciumVitamin D PlaceboCaDPlaceboCaDSupplementsVitamin DOnly Number of women 18,10618, ,56115, HIP FRACTURE Cases Age-adjusted incidence (%) b TOTAL FRACTURE Cases Age-adjusted incidence (%) b MYOCARDIAL INFARCTION Cases Age-adjusted incidence (%) b CORONARY HEART DISEASE Cases Age-adjusted incidence (%) b TOTAL HEART DISEASE Cases Age-adjusted incidence (%) b STROKE Cases Age-adjusted incidence (%) b Age-adjusted annualized incidence rates in the WHI CaD trial and Observational Study

CaD TrialObservational Study All participants No Personal Supplements a Non-users ofCalcium +CalciumVitamin D PlaceboCaDPlaceboCaDSupplementsVitamin DOnly TOTAL CARDIOVASCULAR DISEASE Cases Age-adjusted incidence (%) b COLORECTAL CANCER Cases Age-adjusted incidence (%) b BREAST CANCER Cases Age-adjusted incidence (%) b TOTAL INVASIVE CANCER Cases Age-adjusted incidence (%) b DEATH Cases Age-adjusted incidence (%) b Age-adjusted annualized incidence rates in the WHI CaD trial and Observational Study (continued)

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 < , , , , , , , , , ,1.57 > , , , , ,0.98 Trend test b HR in OS/HR in Trial c , ,1.98 Overall HR d , , , 1.11 TOTAL FRACTURE < , , , , , , , , , ,1.11 > , , , , ,1.16 Trend test b HR in OS/HR in Trial c , ,1.20 Overall HR d , , , 1.14 DEATH < , , , , , , , , , ,1.09 > , , , , ,1.26 Trend test b HR in OS/HR in Trial c , ,1.14 Overall HR d , , , 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

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 < , , , , , , , , , ,1.49 > , , , , ,1.41 Trend test b HR in OS/HR in Trial c , ,1.18 Overall HR d , , , 1.09 CORONARY HEART DISEASE e < , , , , , , , , , ,1.44 > , , , , ,1.33 Trend test b HR in OS/HR in Trial c , ,1.16 Overall HR d , , , 1.04 TOTAL HEART DISEASE f < , , , , , , , , , ,1.23 > , , , , ,1.16 Trend test b HR in OS/HR in Trial c , ,1.05 Overall HR d , , , 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

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 < , , , , , – , , , , ,1.55 > , , , ,1.54 Trend test b HR in OS/HR in Trial c , ,1.09 Overall HR d , , ,1.09 TOTAL CARDIOVASCULAR DISEASE < , , , , , , , , , ,1.19 > , , , , ,1.16 Trend test b HR in OS/HR in Trial c , ,0.99 Overall HR d , , ,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)

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 < , , , , , , , , , ,1.21 > , , , , ,1.45 Trend test b HR in OS/HR in Trial d , ,1.59 Overall HR d , , , 1.12 BREAST CANCER < , , , , , , , , , ,0.95 > , , , , ,1.02 Trend test b HR in OS/HR in Trial c , ,1.84 Overall HR d , , , 1.28 TOTAL INVASIVE CANCER < , , , , , , , , ,0.97 > , , , , ,1.05 Trend test b HR in OS/HR in Trial d , ,1.35 Overall HR d , , , 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

Duration of CaD Supplementation All ParticipantsNo Personal SupplementsAll ParticipantsNo Personal Supplements HR95% CIHR95% CIHR95% CIHR95% CI HIP FRACTURETOTAL FRACTURE < , , , , , , , ,1.13 > , , , ,1.27 Trend test a Overall HR b , , , , 1.03 MYOCARDIAL INFARCTIONCORONARY HEART DISEASE < , , , , , , , ,2.01 > , , , ,1.41 Trend test a Overall HR b , , , , 1.42 TOTAL HEART DISEASESTROKE < , , , , , , , ,3.01 > , , , ,1.76 Trend test a Overall HR b , , , , 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

Duration of CaD Supplementation All ParticipantsNo Personal SupplementsAll ParticipantsNo Personal Supplements HR95% CIHR95% CIHR95% CIHR95% CI TOTAL CARDIOVASCULAR DISEASECOLORECTAL CANCER < , , , , – , , , ,1.93 > , , , ,1.88 Trend test a Overall HR b , , , , 1.27 BREAST CANCERTOTAL INVASIVE CANCER < , , , , , , , ,0.92 > , , , ,1.11 Trend test a Overall HR b , , , , 0.95 DEATH < , , , ,1.26 > , ,1.59 Trend test a Overall HR b , , 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)