Homocysteine levels and the risk of osteoporotic fracture.
BACKGROUND
Very high plasma homocysteine levels are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures.


METHODS
We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or older, who participated in two separate prospective, population-based studies. In the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort 1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam, there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7 years. Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture, with adjustment for age, sex, body-mass index, and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels.


RESULTS
During 11,253 person-years of follow-up, osteoporotic fractures occurred in 191 subjects. The overall multivariable-adjusted relative risk of fracture was 1.4 (95 percent confidence interval, 1.2 to 1.6) for each increase of 1 SD in the natural-log-transformed homocysteine level. The risk was similar in all three cohorts studied, and it was also similar in men and women. A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture (95 percent confidence interval, 1.4 to 2.6). The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture.


CONCLUSIONS
An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women.
van Meurs
Joyce B J
JB
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. j.vanmeurs@erasmusmc.nl
Dhonukshe-Rutten
Rosalie A M
RA
Pluijm
Saskia M F
SM
van der Klift
Marjolein
M
de Jonge
Robert
R
Lindemans
Jan
J
de Groot
Lisette C P G M
LC
Hofman
Albert
A
Witteman
Jacqueline C M
JC
van Leeuwen
Johannes P T M
JP
Breteler
Monique M B
MM
Lips
Paul
P
Pols
Huibert A P
HA
Uitterlinden
André G
AG
D000368:Aged; D015519:Bone Density; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000209:etiology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood* / Q000150:complications; D016016:Proportional Hazards Models; D012306:Risk; D012307:Risk Factors
D006710:Homocysteine