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

Brent C. Taylor, Pamela J. Schreiner, Joseph M. Zmuda, Jia Li, Susan P. Moffett, Thomas J. Beck, Steven R. Cummings, Jocelyn M. Lee, Karen Walker, Kristine E. Ensrud

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)174-180
Number of pages7
JournalBone
Volume39
Issue number1
DOIs
StatePublished - Jul 2006

Fingerprint

Pelvic Bones
Nitric Oxide Synthase Type III
Bone Density
Viperidae
Genotype
Hip
Hip Fractures
Bone and Bones
Spine
Osteoporotic Fractures
Radiography
Nitric Oxide
Incidence

Keywords

  • Aged
  • Bone density
  • Candidate genes
  • Fractures
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

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. / 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.

In: Bone, Vol. 39, No. 1, 07.2006, p. 174-180.

Research output: Contribution to journalArticle

Taylor, BC, Schreiner, PJ, Zmuda, JM, Li, J, Moffett, SP, Beck, TJ, Cummings, SR, Lee, JM, Walker, K & Ensrud, KE 2006, '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', Bone, vol. 39, no. 1, pp. 174-180. https://doi.org/10.1016/j.bone.2005.12.080
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. / 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. In: Bone. 2006 ; Vol. 39, No. 1. pp. 174-180.
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abstract = "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.",
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AU - Zmuda, Joseph M.

AU - Li, Jia

AU - Moffett, Susan P.

AU - Beck, Thomas J.

AU - Cummings, Steven R.

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AU - Walker, Karen

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N2 - 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.

AB - 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.

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