Letter to the Editor
JOURNAL OF WOMEN’S HEALTH Volume 23, Number 3, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/jwh.2013.4699
If You Take It, It Works . Stuti Dang, MD, MPH,1 Silvina Levis, MD,2 and Violet S. Lagari, DO, MPH 3
W
hen presenting the results in the 5-year observational study following the 7-year intervention of the Women’s Health Initiative Calcium and Vitamin D (WHI CaD) Study, the investigators reported that calcium and vitamin D supplementation did not decrease hip fracture.1 The results regarding fracture reduction were disappointing at first glance because the WHI CaD Study was the largest randomized and rigorous clinical trial with the longest duration of exposure and followup testing. The trial was expected to overcome the limitations of previous randomized clinical trials, which were limited by small sample sizes and short duration of follow-up.2 We have concerns that, as presented, the results could send the wrong message to the lay public about the use of calcium and vitamin D supplements. The most important take-home message from the WHI CaD trial is that, when taken, calcium and vitamin D supplementation decrease fracture risk. Several arguments bolster our opinion regarding the positive impact of calcium plus vitamin D on reducing and preventing fractures. 1. The investigators state that over the combined intervention and postintervention followup, averaging 11 years, women who were adherent to the supplement during the intervention had a significant 23% reduction in hip-fracture risk. The investigators also reported a 17% reduction in vertebral-fracture rate. 2. The trial was likely underpowered to reveal the effect on hip fracture, because women age > 70, who are at highest risk for hip fractures, were underenrolled. 3. Several women in the study were taking their own supplements.2 There were women taking as much as 1,200 mg of calcium and 1,000 IU of vitamin D, which was greater than the study dose. This self-use of calcium and vitamin D supplements may have veiled the benefit from the study intervention, because of a ceiling effect. The benefit of calcium and vitamin D supplementation may be best noted in a cohort that is not on supplements.
and vitamin D supplementation. Although, ideally, women should not have been allowed to take their own supplements, we understand the ethical dilemma faced by the WHI CaD trial designers. Strong evidence from previous well-designed trials, some as old as 20 years,4 supports the benefit of calcium and vitamin D on fracture reduction. Special care should be taken to emphasize the main messages along with the associated dilemmas and shortcomings when delivering results from this and similar trials that bear such public health importance. The WHI CaD Study underscores the challenges in designing, conducting, and interpreting results from trials that have a broad-range impact on public health. Author Disclosure Statement
No competing financial interests exist. References
1. Cauley J, Chlebowski RT, Wactawski-Wende J, et al. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: The Women’s Health Initiative. J Womens Health (Larchmt) 2013;22:915–929. 2. Jackson RD, LaCroix AZ, Cauley JA, McGowan J. The Women’s Health Initiative calcium–vitamin D trial: Overview and baseline characteristics of participants. Ann Epidemiol 2003;13:S98–S106. 3. Prentice RL, Pettinger MB, Jackson RD et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 2013;24:567–580. 4. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992;327:1637–1642.
Overall, the WHI data show that, when taken, calcium and vitamin D supplementation reduce hip and vertebral fractures.3 Interpretation of the results was made more difficult because the WHI allowed women to take their own calcium
Address correspondence to: Stuti Dang, MD, MPH Geriatric Research, Education, and Clinical Center Miami VA Healthcare System 1201 NW 16th Street, CLC 207 Miami, FL 33125 E-mail: [email protected]
1 Department of Medicine, Division of Geriatrics and Gerontology, University of Miami Miller School of Medicine; Geriatric Research, Education, and Clinical Center, Miami VA Medical Center, Miami, Florida. 2 Department of Medicine, Division of Geriatrics and Gerontology and Division of Endocrinology, University of Miami Miller School of Medicine; Geriatric Research, Education, and Clinical Center, Miami VA Medical Center, Miami, Florida. 3 Department of Medicine, Division of Endocrinology, University of Miami Miller School of Medicine; Miami VA Medical Center, Miami, Florida.
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JOURNAL OF WOMEN’S HEALTH Volume 23, Number 3, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/jwh.2013.4699
If You Take It, It Works . Stuti Dang, MD, MPH,1 Silvina Levis, MD,2 and Violet S. Lagari, DO, MPH 3
W
hen presenting the results in the 5-year observational study following the 7-year intervention of the Women’s Health Initiative Calcium and Vitamin D (WHI CaD) Study, the investigators reported that calcium and vitamin D supplementation did not decrease hip fracture.1 The results regarding fracture reduction were disappointing at first glance because the WHI CaD Study was the largest randomized and rigorous clinical trial with the longest duration of exposure and followup testing. The trial was expected to overcome the limitations of previous randomized clinical trials, which were limited by small sample sizes and short duration of follow-up.2 We have concerns that, as presented, the results could send the wrong message to the lay public about the use of calcium and vitamin D supplements. The most important take-home message from the WHI CaD trial is that, when taken, calcium and vitamin D supplementation decrease fracture risk. Several arguments bolster our opinion regarding the positive impact of calcium plus vitamin D on reducing and preventing fractures. 1. The investigators state that over the combined intervention and postintervention followup, averaging 11 years, women who were adherent to the supplement during the intervention had a significant 23% reduction in hip-fracture risk. The investigators also reported a 17% reduction in vertebral-fracture rate. 2. The trial was likely underpowered to reveal the effect on hip fracture, because women age > 70, who are at highest risk for hip fractures, were underenrolled. 3. Several women in the study were taking their own supplements.2 There were women taking as much as 1,200 mg of calcium and 1,000 IU of vitamin D, which was greater than the study dose. This self-use of calcium and vitamin D supplements may have veiled the benefit from the study intervention, because of a ceiling effect. The benefit of calcium and vitamin D supplementation may be best noted in a cohort that is not on supplements.
and vitamin D supplementation. Although, ideally, women should not have been allowed to take their own supplements, we understand the ethical dilemma faced by the WHI CaD trial designers. Strong evidence from previous well-designed trials, some as old as 20 years,4 supports the benefit of calcium and vitamin D on fracture reduction. Special care should be taken to emphasize the main messages along with the associated dilemmas and shortcomings when delivering results from this and similar trials that bear such public health importance. The WHI CaD Study underscores the challenges in designing, conducting, and interpreting results from trials that have a broad-range impact on public health. Author Disclosure Statement
No competing financial interests exist. References
1. Cauley J, Chlebowski RT, Wactawski-Wende J, et al. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: The Women’s Health Initiative. J Womens Health (Larchmt) 2013;22:915–929. 2. Jackson RD, LaCroix AZ, Cauley JA, McGowan J. The Women’s Health Initiative calcium–vitamin D trial: Overview and baseline characteristics of participants. Ann Epidemiol 2003;13:S98–S106. 3. Prentice RL, Pettinger MB, Jackson RD et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 2013;24:567–580. 4. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992;327:1637–1642.
Overall, the WHI data show that, when taken, calcium and vitamin D supplementation reduce hip and vertebral fractures.3 Interpretation of the results was made more difficult because the WHI allowed women to take their own calcium
Address correspondence to: Stuti Dang, MD, MPH Geriatric Research, Education, and Clinical Center Miami VA Healthcare System 1201 NW 16th Street, CLC 207 Miami, FL 33125 E-mail: [email protected]
1 Department of Medicine, Division of Geriatrics and Gerontology, University of Miami Miller School of Medicine; Geriatric Research, Education, and Clinical Center, Miami VA Medical Center, Miami, Florida. 2 Department of Medicine, Division of Geriatrics and Gerontology and Division of Endocrinology, University of Miami Miller School of Medicine; Geriatric Research, Education, and Clinical Center, Miami VA Medical Center, Miami, Florida. 3 Department of Medicine, Division of Endocrinology, University of Miami Miller School of Medicine; Miami VA Medical Center, Miami, Florida.
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