Thank you for the opportunity to express our views on the U.S. Preventive Services Task Force (USPSTF) draft recommendations and evidence review on Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Adults. The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work.
We support the efforts of the U.S. Preventive Services Task Force to re-evaluate the benefits and harms of preventive medication for fractures in adults in light of new research studies which focus on the harms and benefits of calcium supplementation, the risk of kidney stones with combined vitamin D and calcium treatment, and the cardiovascular safety of vitamin D.
Based on the USPSTF’s comprehensive review, we agree that it is difficult to draw from available evidence whether calcium, Vitamin D, or the combination provide any clear and conclusive benefit. However, we suggest that the evidence for harms is more certain.
We support the USPSTF in maintaining a “D” rating recommending against supplementation of vitamin D and calcium in postmenopausal women because the evidence from the Women’s Health Initiative (WHI) study clearly contradicts such a recommendation. However, we have several concerns about the evidence review and offer some suggestions to improve the draft recommendations:
1. Based on the WHI study, we agree that generally the data support that combined supplementation of Vitamin D and calcium does not prevent fractures. However, the subgroup analyses for hip fractures by age indicate that age may significantly modify the treatment effect in a surprising way. For example, women ages 50 to 59 who took vitamin D and calcium had double the risk of fracture than those in the placebo group. While the risk was still low, the difference was statistically significant. In contrast, the
risk of fracture for women ages 60 to 69 taking the two supplements was no different than women taking placebo. It is essential that women be informed that these supplements are not beneficial and in fact may be harmful for women 50-59 years old. Therefore, we strongly urge the USPSTF to include a separate and clear “D” rating recommending against calcium and vitamin D supplementation for women ages 50-59 due to significant increased risk of hip fracture.
2. We agree with the Task Force review team that available evidence is limited regarding the effects of calcium supplementation alone. While the pooled data indicate that calcium supplementation may decrease absolute risk of any fracture by 2.4 percent, the Reid et al. study demonstrated that this benefit is significantly offset by a 1.7 percent increased absolute risk of hip fracture, which is often the most serious type of fracture. Moreover, the cardiovascular safety trends for calcium supplementation, although not statistically significant, are not reassuring. For example, the smaller studies reviewed by the Task Force suggest that those taking calcium experienced a 10-50% increased risk for cardiovascular disease compared to those not taking it. Given the lack of clear evidence of benefits and the risks of hip fracture and cardiovascular disease, we strongly urge the USPSTF to include a separate and clear “D” rating recommending against calcium supplementation for the prevention of fractures.
3. We appreciate the Task Force’s review of the risk of kidney stones with supplementation. Even when harms are small, they are worthy of attention when there are no clear benefits. We know that calcium alone does not increase the risk of kidney stones, but pooled estimates indicate that calcium plus vitamin D increased risk of kidney stones by 18% relative to placebo. We could infer that Vitamin D is driving the increased risk, but there were no studies included on the risks of Vitamin D supplementation alone to determine this conclusively. Therefore, we suggest that the risk of kidney stones outweighs the unestablished benefits of vitamin D supplementation and we strongly urge the USPSTF to include a “D” rating recommending against vitamin D supplementation alone or in combination with calcium.
In conclusion, we agree with maintaining much of the 2013 recommendations, but we strongly suggest that the USPSTF provide separate and clear “D” recommendations against calcium and vitamin D supplementation for women ages 50-59. We also suggest that, although not statistically significant, the cardiovascular harms and increased risk of hip fractures nullify uncertain benefits of calcium supplementation for fracture prevention. Last, we suggest that the statistically significant increased risk of kidney stones associated with combined calcium and vitamin D supplementation indicate that harms outweigh benefits. Since it seems possible that vitamin D supplementation may be driving the increased risk of kidney stones, we suggest the USPSTF recommend against its use for prevention of fractures.
Overall, the evidence demonstrates that these supplements are not beneficial, and they may pose serious risks. “I” recommendations are misleading and do not provide a sufficiently clear indication of harm. It would be unfair to patients and providers to finalize the proposed draft recommendations when the evidence clearly indicates otherwise. We urge that the USPSTF reconsider and revise their recommendations as outlined above.
For questions or more information, please contact Diana Zuckerman, PhD, at email@example.com.
Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Adults: Preventive Medication.U.S. Preventive Services Task Force. October 2017. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/vitamin-d-calcium-or-combined-supplementation-for-the-primary-prevention-of-fractures-in-adults-preventive-medication