Calcium plus vitamin D supplementation and the risk of fractures.
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 [corrected] 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.).
Jackson
Rebecca D
RD
Division of Endocrinology, Ohio State University, 485 McCampbell, 1581 Dodd Dr., Columbus, OH 43210, USA. jackson.20@osu.edu
LaCroix
Andrea Z
AZ
Gass
Margery
M
Wallace
Robert B
RB
Robbins
John
J
Lewis
Cora E
CE
Bassford
Tamsen
T
Beresford
Shirley A A
SA
Black
Henry R
HR
Blanchette
Patricia
P
Bonds
Denise E
DE
Brunner
Robert L
RL
Brzyski
Robert G
RG
Caan
Bette
B
Cauley
Jane A
JA
Chlebowski
Rowan T
RT
Cummings
Steven R
SR
Granek
Iris
I
Hays
Jennifer
J
Heiss
Gerardo
G
Hendrix
Susan L
SL
Howard
Barbara V
BV
Hsia
Judith
J
Hubbell
F Allan
FA
Johnson
Karen C
KC
Judd
Howard
H
Kotchen
Jane Morley
JM
Kuller
Lewis H
LH
Langer
Robert D
RD
Lasser
Norman L
NL
Limacher
Marian C
MC
Ludlam
Shari
S
Manson
JoAnn E
JE
Margolis
Karen L
KL
McGowan
Joan
J
Ockene
Judith K
JK
O'Sullivan
Mary Jo
MJ
Phillips
Lawrence
L
Prentice
Ross L
RL
Sarto
Gloria E
GE
Stefanick
Marcia L
ML
Van Horn
Linda
L
Wactawski-Wende
Jean
J
Whitlock
Evelyn
E
Anderson
Garnet L
GL
Assaf
Annlouise R
AR
Barad
David
D
D000368:Aged; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000627:therapeutic use; D002119:Calcium Carbonate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D015914:Estrogen Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006620:Hip Fractures / Q000517:prevention & control; D006801:Humans; D007669:Kidney Calculi / Q000139:chemically induced; D008875:Middle Aged; D010349:Patient Compliance; D017698:Postmenopause; D016016:Proportional Hazards Models; D012306:Risk; D016103:Spinal Fractures / Q000517:prevention & control; D014807:Vitamin D / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
D004338:Drug Combinations; D014807:Vitamin D; D002119:Calcium Carbonate; D002118:Calcium