The strongest evidence for benefit is for hip fracture where calcium and vitamin D supplementation yielded a noteworthy reduction after 5 years of treatment among women not taking personal supplements,
with HR (95 % CI) of 0.62 (0.38, 1.00). It is important to note that hip fracture buy RepSox was the sole primary outcome in the CaD trial, reducing multiple testing limitations. Nevertheless, a cautious interpretation is needed since this is a finding in the no personal supplements subset, while the corresponding overall trial result (HR of 0.82, 95 % CI of 0.61 to 1.12) is not significant. However, the likelihood of a hip fracture risk reduction is enhanced by a significant (P = 0.02) trend of reducing HR with duration of supplementation in the no personal supplements Alpelisib manufacturer group and by nominally significant risk reductions over the entire follow-up period among adherent women, both in the overall trial cohort and in the no personal supplements subset (Table 6). For example, these adherence-adjusted analyses yield an HR (95 % CI) of 0.24 (0.07, 0.84) following 5 or more years of use among women in the no personal supplements group, suggesting that the public health implications of supplementation could be substantial. Moreover, the biological plausibility of this finding
is also supported by higher (P < 0.01) hip bone mineral density (BMD) in the active treatment versus
placebo group at 2, 5, and 8 years ADAM7 of follow-up . Supplementary Figure 1 shows average hip, spine, and whole body BMD at baseline, and at 2, 5, and 8 years later, by randomization group, overall, and in the subset of women not using personal supplements, with and without restriction to women adhering to assigned study pills. A larger hip BMD in the intervention group is evident overall, and among women not taking personal supplements, and the difference is enhanced among adherent women. WHI data provide little support for an influence of calcium and vitamin D supplementation on coronary heart disease risk or Tozasertib cardiovascular disease risk more generally. Women randomized to CaD do not have a significantly elevated risk of MI, CHD, total heart disease, stroke or total cardiovascular disease, either overall or in the subset not using supplements at baseline. Furthermore, any suggestion of an early MI elevation is dampened by multiple testing considerations, since none of the several cardiovascular disease categories considered were among the designated primary or secondary trial outcome and any such suggestion was not enhanced by restriction to women who adhered to study medications. Also, there was no suggested MI elevation in the OS.