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.).
Division of Endocrinology, Ohio State University, 485 McCampbell, 1581 Dodd Dr., Columbus, OH 43210, USA. jackson.20@osu.edu
Rebecca D
RD
Jackson
Andrea Z
AZ
LaCroix
Margery
M
Gass
Robert B
RB
Wallace
John
J
Robbins
Cora E
CE
Lewis
Tamsen
T
Bassford
Shirley A A
SA
Beresford
Henry R
HR
Black
Patricia
P
Blanchette
Denise E
DE
Bonds
Robert L
RL
Brunner
Robert G
RG
Brzyski
Bette
B
Caan
Jane A
JA
Cauley
Rowan T
RT
Chlebowski
Steven R
SR
Cummings
Iris
I
Granek
Jennifer
J
Hays
Gerardo
G
Heiss
Susan L
SL
Hendrix
Barbara V
BV
Howard
Judith
J
Hsia
F Allan
FA
Hubbell
Karen C
KC
Johnson
Howard
H
Judd
Jane Morley
JM
Kotchen
Lewis H
LH
Kuller
Robert D
RD
Langer
Norman L
NL
Lasser
Marian C
MC
Limacher
Shari
S
Ludlam
JoAnn E
JE
Manson
Karen L
KL
Margolis
Joan
J
McGowan
Judith K
JK
Ockene
Mary Jo
MJ
O'Sullivan
Lawrence
L
Phillips
Ross L
RL
Prentice
Gloria E
GE
Sarto
Marcia L
ML
Stefanick
Linda
L
Van Horn
Jean
J
Wactawski-Wende
Evelyn
E
Whitlock
Garnet L
GL
Anderson
Annlouise R
AR
Assaf
David
D
Barad
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