Calcium plus vitamin D supplementation and the risk of fractures

Rebecca D. Jackson, Andrea Z. LaCroix, Margery Gass, Robert B. Wallace, John Robbins, Cora E. Lewis, Tamsen Bassford, Shirley A.A. Beresford, Henry R. Black, Patricia Blanchette, Denise E. Bonds, Robert L. Brunner, Robert G. Brzyski, Bette Caan, Jane A. Cauley, Rowan T. Chlebowski, Steven R. Cummings, Iris Granek, Jennifer Hays, Gerardo HeissSusan L. Hendrix, Barbara V. Howard, Judith Hsia, F. Allan Hubbell, Karen Johnson, Howard Judd, Jane Morley Kotchen, Lewis H. Kuller, Robert D. Langer, Norman L. Lasser, Marian C. Limacher, Shari Ludlam, Joann E. Manson, Karen L. Margolis, Joan McGowan, Judith K. Ockene, Mary Jo O'Sullivan, Lawrence Phillips, Ross L. Prentice, Gloria E. Sarto, Marcia L. Stefanick, Linda Van Horn, Jean Wactawski-Wende, Evelyn Whitlock, Garnet L. Anderson, Annlouise R. Assaf, David Barad

Research output: Contribution to journalArticle

1238 Citations (Scopus)

Abstract

BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.)

Original languageEnglish (US)
Pages (from-to)669-683
Number of pages15
JournalNew England Journal of Medicine
Volume354
Issue number7
DOIs
StatePublished - Feb 16 2006

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Vitamin D
Hip Fractures
Calcium
Pelvic Bones
Bone Density
Kidney Calculi
Women's Health
Confidence Intervals
Placebos
Intention to Treat Analysis
Calcium Carbonate
Cholecalciferol
Spine
Clinical Trials
Serum

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Jackson, R. D., LaCroix, A. Z., Gass, M., Wallace, R. B., Robbins, J., Lewis, C. E., ... Barad, D. (2006). Calcium plus vitamin D supplementation and the risk of fractures. New England Journal of Medicine, 354(7), 669-683. https://doi.org/10.1056/NEJMoa055218

Calcium plus vitamin D supplementation and the risk of fractures. / Jackson, Rebecca D.; LaCroix, Andrea Z.; Gass, Margery; Wallace, Robert B.; Robbins, John; Lewis, Cora E.; Bassford, Tamsen; Beresford, Shirley A.A.; Black, Henry R.; Blanchette, Patricia; Bonds, Denise E.; Brunner, Robert L.; Brzyski, Robert G.; Caan, Bette; Cauley, Jane A.; Chlebowski, Rowan T.; Cummings, Steven R.; Granek, Iris; Hays, Jennifer; Heiss, Gerardo; Hendrix, Susan L.; Howard, Barbara V.; Hsia, Judith; Hubbell, F. Allan; Johnson, Karen; Judd, Howard; Kotchen, Jane Morley; Kuller, Lewis H.; Langer, Robert D.; Lasser, Norman L.; Limacher, Marian C.; Ludlam, Shari; Manson, Joann E.; Margolis, Karen L.; McGowan, Joan; Ockene, Judith K.; O'Sullivan, Mary Jo; Phillips, Lawrence; Prentice, Ross L.; Sarto, Gloria E.; Stefanick, Marcia L.; Van Horn, Linda; Wactawski-Wende, Jean; Whitlock, Evelyn; Anderson, Garnet L.; Assaf, Annlouise R.; Barad, David.

In: New England Journal of Medicine, Vol. 354, No. 7, 16.02.2006, p. 669-683.

Research output: Contribution to journalArticle

Jackson, RD, LaCroix, AZ, Gass, M, Wallace, RB, Robbins, J, Lewis, CE, Bassford, T, Beresford, SAA, Black, HR, Blanchette, P, Bonds, DE, Brunner, RL, Brzyski, RG, Caan, B, Cauley, JA, Chlebowski, RT, Cummings, SR, Granek, I, Hays, J, Heiss, G, Hendrix, SL, Howard, BV, Hsia, J, Hubbell, FA, Johnson, K, Judd, H, Kotchen, JM, Kuller, LH, Langer, RD, Lasser, NL, Limacher, MC, Ludlam, S, Manson, JE, Margolis, KL, McGowan, J, Ockene, JK, O'Sullivan, MJ, Phillips, L, Prentice, RL, Sarto, GE, Stefanick, ML, Van Horn, L, Wactawski-Wende, J, Whitlock, E, Anderson, GL, Assaf, AR & Barad, D 2006, 'Calcium plus vitamin D supplementation and the risk of fractures', New England Journal of Medicine, vol. 354, no. 7, pp. 669-683. https://doi.org/10.1056/NEJMoa055218
Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE et al. Calcium plus vitamin D supplementation and the risk of fractures. New England Journal of Medicine. 2006 Feb 16;354(7):669-683. https://doi.org/10.1056/NEJMoa055218
Jackson, Rebecca D. ; LaCroix, Andrea Z. ; Gass, Margery ; Wallace, Robert B. ; Robbins, John ; Lewis, Cora E. ; Bassford, Tamsen ; Beresford, Shirley A.A. ; Black, Henry R. ; Blanchette, Patricia ; Bonds, Denise E. ; Brunner, Robert L. ; Brzyski, Robert G. ; Caan, Bette ; Cauley, Jane A. ; Chlebowski, Rowan T. ; Cummings, Steven R. ; Granek, Iris ; Hays, Jennifer ; Heiss, Gerardo ; Hendrix, Susan L. ; Howard, Barbara V. ; Hsia, Judith ; Hubbell, F. Allan ; Johnson, Karen ; Judd, Howard ; Kotchen, Jane Morley ; Kuller, Lewis H. ; Langer, Robert D. ; Lasser, Norman L. ; Limacher, Marian C. ; Ludlam, Shari ; Manson, Joann E. ; Margolis, Karen L. ; McGowan, Joan ; Ockene, Judith K. ; O'Sullivan, Mary Jo ; Phillips, Lawrence ; Prentice, Ross L. ; Sarto, Gloria E. ; Stefanick, Marcia L. ; Van Horn, Linda ; Wactawski-Wende, Jean ; Whitlock, Evelyn ; Anderson, Garnet L. ; Assaf, Annlouise R. ; Barad, David. / Calcium plus vitamin D supplementation and the risk of fractures. In: New England Journal of Medicine. 2006 ; Vol. 354, No. 7. pp. 669-683.
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abstract = "BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.)",
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TY - JOUR

T1 - Calcium plus vitamin D supplementation and the risk of fractures

AU - Jackson, Rebecca D.

AU - LaCroix, Andrea Z.

AU - Gass, Margery

AU - Wallace, Robert B.

AU - Robbins, John

AU - Lewis, Cora E.

AU - Bassford, Tamsen

AU - Beresford, Shirley A.A.

AU - Black, Henry R.

AU - Blanchette, Patricia

AU - Bonds, Denise E.

AU - Brunner, Robert L.

AU - Brzyski, Robert G.

AU - Caan, Bette

AU - Cauley, Jane A.

AU - Chlebowski, Rowan T.

AU - Cummings, Steven R.

AU - Granek, Iris

AU - Hays, Jennifer

AU - Heiss, Gerardo

AU - Hendrix, Susan L.

AU - Howard, Barbara V.

AU - Hsia, Judith

AU - Hubbell, F. Allan

AU - Johnson, Karen

AU - Judd, Howard

AU - Kotchen, Jane Morley

AU - Kuller, Lewis H.

AU - Langer, Robert D.

AU - Lasser, Norman L.

AU - Limacher, Marian C.

AU - Ludlam, Shari

AU - Manson, Joann E.

AU - Margolis, Karen L.

AU - McGowan, Joan

AU - Ockene, Judith K.

AU - O'Sullivan, Mary Jo

AU - Phillips, Lawrence

AU - Prentice, Ross L.

AU - Sarto, Gloria E.

AU - Stefanick, Marcia L.

AU - Van Horn, Linda

AU - Wactawski-Wende, Jean

AU - Whitlock, Evelyn

AU - Anderson, Garnet L.

AU - Assaf, Annlouise R.

AU - Barad, David

PY - 2006/2/16

Y1 - 2006/2/16

N2 - BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.)

AB - BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.)

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DO - 10.1056/NEJMoa055218

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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