This study aims to test the added value of calcium and vitamin D (CaD) in fracture prevention among women taking postmenopausal hormone therapy (HT).
This is a prospective, partial-factorial, randomized, controlled, double-blind trial among Women’s Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years. A total of 27,347 women were randomized to HT (0.625 mg of conjugated estrogens alone, or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily), and 36,282 women were randomized to 1,000 mg of elemental calcium (carbonate) plus 400 IU of vitamin D3 daily, each compared with placebo. A total of 16,089 women participated in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density.
Interaction between HT and CaD on hip fracture (P interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (hazard ratio [HR], 0.59; 95% CI, 0.38-0.93) than among women assigned to placebo (HR, 1.20; 95% CI, 0.85-1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 95% CI, 0.28-0.66) than among women assigned to placebo (HR, 0.87; 95% CI, 0.60-1.26). CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake. There was no interaction between HT and CaD on change in hip or spine bone mineral density.
Postmenopausal women at normal risk for hip fracture who are on CaD supplementation experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake.
From the 1Department of Medicine, University of California Davis, Sacramento, CA; 2Fred Hutchinson Cancer Research Center, Seattle, WA; 3Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; 4Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; 5Veterans Affairs Medical Center, Memphis, TN; 6Department of Medicine, University of Tennessee Health Science Center, Memphis, TN; 7Department of Medicine, Ohio State University, Columbus, OH; 8Division of Preventive Medicine, University of Alabama, Birmingham, AL; 9Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN; 10Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, WI; 11Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA; and 12Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, NY.
Received February 12, 2013; revised and accepted April 1, 2013.
Funding/support: This research was partially funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.
Financial disclosure/conflicts of interest: C.E.L. has received a grant from Novo Nordisk. R.J. has received a grant from Pfizer.
Address correspondence to: John A. Robbins, MD, MHS, Department of Medicine, University of California Davis, Suite 2400, 4150 V Street, Sacramento, CA 95817. E-mail: firstname.lastname@example.org