Osteoprotegerin Lys3Asn polymorphism and the risk of fracture in older women.
BACKGROUND
Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator nuclear factor kappa-beta that blocks osteoclastic bone resorption.


OBJECTIVE
We investigated the association between a Lys3Asn polymorphism in the OPG gene and bone mineral density (BMD), and the risk of fracture in 6695 women aged 65 yr and older participating in the Study of Osteoporotic Fractures.


METHODS
BMD was measured using either single-photon absorptiometry (Osteon Osteoanalyzer; Dove Medical Group, Los Angeles, CA) or dual-energy x-ray absorptiometry (Hologic QDR 1000; Hologic, Inc., Bedford, MA). Incident fractures were confirmed by physician adjudication of radiology reports. Genotyping was performed using an immobilized probe-based assay.


RESULTS
Women who were homozygous for the minor G (Lys) allele had significantly lower BMD at the intertrochanter, distal radius, lumbar spine, and calcaneus than those with the C (Asn) allele. There were 701 incident hip fractures during 13.6-yr follow-up (91,249 person-years), including 362 femoral neck and 333 intertrochanteric hip fractures. Women with the C/C (Asn-Asn) genotype had a 51% higher risk of femoral neck fracture (95% confidence interval, 1.13-2.02) and 26% higher risk of hip fracture (95% confidence interval, 1.02-1.54) than those with the G/G (Lys-Lys) genotype. These associations were independent of BMD. Intertrochanteric fractures were not associated with the Lys3Asn polymorphism.


CONCLUSIONS
These results require confirmation but suggest a role for the OPG Lys3Asn polymorphism in the genetic susceptibility to hip fractures among older white women.
Moffett
S P
SP
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA.
Oakley
J I
JI
Cauley
J A
JA
Lui
L Y
LY
Ensrud
K E
KE
Taylor
B C
BC
Hillier
T A
TA
Hochberg
M C
MC
Li
J
J
Cayabyab
S
S
Lee
J M
JM
Peltz
G
G
Cummings
S R
SR
Zmuda
J M
JM
D000368:Aged; D015519:Bone Density; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006620:Hip Fractures / Q000209:etiology*; D006801:Humans; D053244:Osteoprotegerin / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors
D053244:Osteoprotegerin