当前位置: 首页 > 期刊 > 《新英格兰医药杂志》 > 2006年第21期 > 正文
编号:11327647
Calcium plus Vitamin D and the Risk of Fractures
http://www.100md.com 《新英格兰医药杂志》
     To the Editor: The increased incidence of nephrolithiasis among patients taking supplemental calcium carbonate that was reported by Jackson et al. (Feb. 16 issue)1 might have been avoided if calcium citrate had been given. It has been shown that urinary calcium oxalate crystals that form in the presence of hypercalciuria and hyperoxaluria develop into clinically important stones only after aggregation into larger particles. This aggregation is inhibited by citrate at physiologic concentrations.2,3

    The data in Table 3 in the report suggest that calcium and vitamin D reduced the incidence of hip fracture more in older patients than in younger patients, which is not unexpected, given the pathophysiological differences between perimenopausal bone loss and senile bone loss.4 Measurement of parathyroid hormone levels to assess the adequacy of vitamin D intake might have helped in the interpretation of these findings.5,6 The dose of supplementary vitamin D used in this study, assuming it was the sole or major source of vitamin D, may have been too low to have had a more dramatic effect in either age group.

    Susan Terris, M.D., Ph.D.

    25 Coleman Ave.

    Red Bank, NJ 07701

    References

    Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-683.

    Glauser A, Hochreiter W, Jaeger P, Hess B. Determinants of urinary excretion of Tamm-Horsfall protein in non-selected kidney stone formers and healthy subjects. Nephrol Dial Transplant 2000;15:1580-1587.

    Hess B, Jordi S, Zipperle L, Ettinger E, Giovanoli R. Citrate determines calcium oxalate crystallization kinetics and crystal morphology -- studies in the presence of Tamm-Horsfall protein of a healthy subject and a severely recurrent calcium stone former. Nephrol Dial Transplant 2000;15:366-374.

    Riggs BL. Overview of osteoporosis. West J Med 1991;154:63-77.

    Kinyamu HK, Gallagher JC, Rafferty KA, Balhorn KE. Dietary calcium and vitamin D intake in elderly women: effect on serum parathyroid hormone and vitamin D metabolites. Am J Clin Nutr 1998;67:342-348.

    Holick MF, Siris ES, Binkley N, et al. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 2005;90:3215-3224.

    To the Editor: Although Jackson and coworkers conclude that calcium and vitamin D supplementation did not significantly reduce fracture rates among women 50 to 79 years of age, their observations can be interpreted to provide support for a different conclusion. Since it has been well established that bone mineral density (BMD) decreases progressively in postmenopausal women who are not treated for bone loss, one is struck by the authors' finding that the mean BMD for the total spine and the whole body in the control subjects increased steadily over the nine years of the study, and that the BMD for the total hip remained essentially unchanged, as shown in Figure 2 of the article by Jackson et al. This phenomenon was almost surely influenced by the large proportion of control subjects who were already taking calcium or vitamin D at "therapeutic" doses. One would expect improved BMD to be associated with fewer fractures; the investigators did, in fact, find fracture rates for both control subjects and treated subjects to be less than half the rate historically anticipated. It is also not surprising that the administration of additional calcium and vitamin D to treated subjects further reduced hip fractures only to a limited degree, particularly since the optimal intakes of both are unknown.

    Gerson T. Lesser, M.D.

    Mount Sinai School of Medicine

    New York, NY 10029

    glesser@jhha.org

    To the Editor: The results of the Women's Health Initiative (WHI) trial of calcium with vitamin D reveal that calcium and vitamin D supplementation (1000 mg of calcium carbonate with 400 IU of vitamin D) did not lower fracture rates but did increase the risk of kidney stones in calcium-replete postmenopausal women (mean intake, 1150 mg per day) whose intake of vitamin D was insufficient (serum 25-hydroxyvitamin D, 48 nmol per liter). How should these results influence clinical practice? They should have no effect on the evidence-based recommendation that postmenopausal women, who typically consume 600 mg of elemental calcium per day, should increase their calcium intake to 1200 mg per day.1 Similarly, the results should not deter physicians from recommending 800 IU of vitamin D per day — the amount the average postmenopausal woman needs to raise her serum 25-hydroxyvitamin D level to that needed to lower the risk of fracture (75 nmol per liter).2 Finally, the increased risk of kidney stones among the women in the study who were consuming a mean of 2150 mg per day of calcium (usual mean intake plus supplement), as compared with those consuming 1150 mg per day, should not be assumed to apply to women who increase their intake to 1200 mg per day. It is important that the WHI trial not be used to sanction the inadequate intake of calcium and vitamin D that is so widespread among postmenopausal women today.

    Bess Dawson-Hughes, M.D.

    Tufts University

    Boston, MA 02111

    bess.dawson-hughes@tufts.edu

    Dr. Dawson-Hughes reports having received an honorarium from GlaxoSmithKline.

    References

    Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary reference intakes: for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, D.C.: National Academy Press, 1997.

    Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int 2005;16:713-716.

    The authors reply: Dr. Terris notes that use of supplemental calcium citrate, instead of calcium carbonate, may lessen the risk of kidney stones observed in the WHI calcium with vitamin D trial, and we agree. However, calcium carbonate, perhaps because of its greater affordability, is still the most common form of calcium supplementation used in the United States. The present study did not have the power to examine changes in parathyroid hormone levels among women with hip fracture and controls, because stored specimens were available after randomization for a subsample of the trial population that consisted of only 6 percent of the subjects.

    Dr. Lesser attributes the low rate of hip fracture in the placebo group to the already high levels of calcium intake at baseline. As we report, there are other powerful fracture-lowering factors that probably also contributed, including high levels of hormone use and body-mass index and the enrollment of fewer women over 70 years of age than expected. Nonetheless, we believe that the trial results provide several indications that calcium intake does reduce the risk of hip fracture. Calcium and vitamin D supplementation reduced the risk of hip fracture by 29 percent among women with an adherence of 80 percent or more, 21 percent among those 60 years of age or older at enrollment, and 30 percent among those not taking other calcium supplements during the trial (all 95 percent confidence intervals for the corresponding hazard ratios exclude 1). In fact, we believe that these data support current recommendations for adequate calcium intake.

    Two other clarifications are important to make in the interpretation of the trial results. First, the increased risk of kidney stones was not associated with high baseline calcium intake. Our preliminary analyses indicated no interaction with baseline calcium intake and, in fact, a somewhat greater risk among women with a lower total calcium intake at baseline. The factors contributing to an increase in the risk of kidney stones are under investigation. Second, some have disregarded the greater effects of the calcium-plus-vitamin-D intervention in older women as being uninterpretable, claiming that the randomization was no longer intact in subgroups defined according to age. In fact, the randomization of women in all the WHI trials was stratified according to age in order to ensure that measured and unmeasured characteristics would be balanced within the age groups. There are other caveats associated with subgroup analysis (e.g., multiple comparisons and lack of power), but in the WHI trials, age-specific analyses are protected from confounding by the randomized design.

    Rebecca D. Jackson, M.D.

    Ohio State University

    Columbus, OH 43210

    jackson.20@osu.edu

    Andrea Z. LaCroix, Ph.D.

    Fred Hutchinson Cancer Research Center

    Seattle, WA 98109

    for the Women's Health Initiative Investigators