Association of endothelial nitric oxide synthase genotypes with bone mineral density, bone loss, hip structure, and risk of fracture in older women: The SOF study

Nitric oxide (NO) is an important bone-signaling molecule. We examined the associations between the Glu298Asp polymorphism of NOS3, indices of bone strength, and the incidence of fracture among 6691 women aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Calcaneal BMD was meas...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2006-07, Vol.39 (1), p.174-180
Main Authors: Taylor, Brent C., Schreiner, Pamela J., Zmuda, Joseph M., Li, Jia, Moffett, Susan P., Beck, Thomas J., Cummings, Steven R., Lee, Jocelyn M., Walker, Karen, Ensrud, Kristine E.
Format: Article
Language:English
Subjects:
Age Factors
Aged
Aged, 80 and over
Amino Acid Substitution
Asparagine - metabolism
Biological and medical sciences
Bone Density
Calcaneus - physiology
Candidate genes
Cohort Studies
European Continental Ancestry Group
Female
Follow-Up Studies
Fractures
Fractures, Bone - complications
Fractures, Bone - epidemiology
Fundamental and applied biological sciences. Psychology
Gene Frequency
Genotype
Heterozygote
Hip - physiology
Hip Fractures - complications
Hip Fractures - diagnostic imaging
Hip Fractures - epidemiology
Humans
Incidence
Injuries of the limb. Injuries of the spine
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Nitric oxide synthase
Nitric Oxide Synthase Type III - genetics
Osteoarticular system. Muscles
Osteoporosis, Postmenopausal
Polymorphism, Genetic
Prevalence
Prospective Studies
Radiodiagnosis. Nmr imagery. Nmr spectrometry
Radiography
Risk Factors
Spinal Fractures - complications
Spinal Fractures - diagnostic imaging
Time Factors
Traumas. Diseases due to physical agents
United States - epidemiology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:Nitric oxide (NO) is an important bone-signaling molecule. We examined the associations between the Glu298Asp polymorphism of NOS3, indices of bone strength, and the incidence of fracture among 6691 women aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Calcaneal BMD was measured at an initial exam and after an average of 5.9 years of follow-up. Hip BMD was measured at an initial exam and after 3.7 years of follow-up. Baseline spine BMD and hip structural parameters were measured. Incident hip fractures were confirmed by review of radiographic reports; follow-up was greater than 98% complete. Incident vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. The frequencies of the NOS3 Glu298Asp genotypes were Glu/Glu = 46.2%, Glu/Asp = 42.7%, and Asp/Asp = 11.1%. There were no significant associations between NOS3 genotypes and initial calcaneal BMD, hip BMD, or rate of change in hip or calcaneal BMD. None of the hip structural parameters differed substantially by genotype. NOS3 genotype was not significantly associated with either incident or prevalent radiographic vertebral fractures. Women with the heterozygous Glu/Asp genotype had a borderline statistically significantly lower rate of hip fracture than either the Glu/Glu genotype (HR = 0.87, 95% CI: 0.74, 1.01) or the Asp/Asp genotype (HR = 0.78, 95% CI: 0.62, 0.98). In conclusion, the Glu298Asp polymorphism does not contribute substantially or consistently to indices of bone strength in this sample of older white women, although our findings suggest allelic variation at the NOS3 locus maybe associated with hip fracture risk. Confirmation of these findings is needed in other populations and with additional markers within and flanking the NOS3 gene region.
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2005.12.080