Tumor necrosis factor-α polymorphism, bone strength phenotypes, and the risk of fracture in older women

S. P. Moffett, J. M. Zmuda, J. I. Oakley, T. J. Beck, J. A. Cauley, K. L. Stone, Li Yung Lui, K. E. Ensrud, T. A. Hillier, M. C. Hochberg, P. Morin, G. Peltz, D. Greene, S. R. Cummings

Research output: Contribution to journalArticle

Abstract

TNFα is a proinflammatory cytokine that promotes osteoclastic bone resorption. We evaluated the association between a G-308A polymorphism (rs1800629) at the TNFA locus and osteoporosis phenotypes in 4306 older women participating in the Study of Osteoporotic Fractures. Femoral neck bone mineral density (BMD) and structural geometry were measured using dual-energy x-ray absorptiometry and hip structural analysis. Incident fractures were confirmed by physician adjudication of radiology reports. Despite similar femoral neck BMD, women with the A/A genotype had greater subperiosteal width (P = 0.01) and endocortical diameter (P = 0.03) than those with the G/G genotype. The net result of these structural differences was that there was a greater distribution of bone mass away from the neutral axis of the femoral neck in women with the A/A genotype, resulting in greater indices of bone bending strength (cross-sectional moment of inertia: P = 0.004; section modulus: P = 0.003). Among 376 incident hip fractures during 12.1 yr of follow-up, a 22% decrease in the risk of hip fracture was seen per copy of the A allele (relative risk 0.78; 95% confidence interval 0.63, 0.96), which was not influenced by adjustments for potential confounding factors, BMD, or bone strength indices. The G-308A polymorphism was not associated with a reduced risk of other fractures. These results suggest a potential role of genetic variation in TNFα in the etiology of osteoporosis.

Original languageEnglish (US)
Pages (from-to)3491-3497
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number6
DOIs
StatePublished - Jun 2005

Fingerprint

Femur Neck
Polymorphism
Bone Density
Bone
Tumor Necrosis Factor-alpha
Genotype
Hip Fractures
Phenotype
Bone and Bones
Osteoporosis
Osteoporotic Fractures
Minerals
Bone Resorption
Radiology
Hip
Alleles
X-Rays
Confidence Intervals
Cytokines
Physicians

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Moffett, S. P., Zmuda, J. M., Oakley, J. I., Beck, T. J., Cauley, J. A., Stone, K. L., ... Cummings, S. R. (2005). Tumor necrosis factor-α polymorphism, bone strength phenotypes, and the risk of fracture in older women. Journal of Clinical Endocrinology and Metabolism, 90(6), 3491-3497. https://doi.org/10.1210/jc.2004-2235

Tumor necrosis factor-α polymorphism, bone strength phenotypes, and the risk of fracture in older women. / Moffett, S. P.; Zmuda, J. M.; Oakley, J. I.; Beck, T. J.; Cauley, J. A.; Stone, K. L.; Lui, Li Yung; Ensrud, K. E.; Hillier, T. A.; Hochberg, M. C.; Morin, P.; Peltz, G.; Greene, D.; Cummings, S. R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 6, 06.2005, p. 3491-3497.

Research output: Contribution to journalArticle

Moffett, SP, Zmuda, JM, Oakley, JI, Beck, TJ, Cauley, JA, Stone, KL, Lui, LY, Ensrud, KE, Hillier, TA, Hochberg, MC, Morin, P, Peltz, G, Greene, D & Cummings, SR 2005, 'Tumor necrosis factor-α polymorphism, bone strength phenotypes, and the risk of fracture in older women', Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 6, pp. 3491-3497. https://doi.org/10.1210/jc.2004-2235
Moffett, S. P. ; Zmuda, J. M. ; Oakley, J. I. ; Beck, T. J. ; Cauley, J. A. ; Stone, K. L. ; Lui, Li Yung ; Ensrud, K. E. ; Hillier, T. A. ; Hochberg, M. C. ; Morin, P. ; Peltz, G. ; Greene, D. ; Cummings, S. R. / Tumor necrosis factor-α polymorphism, bone strength phenotypes, and the risk of fracture in older women. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 6. pp. 3491-3497.
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AU - Zmuda, J. M.

AU - Oakley, J. I.

AU - Beck, T. J.

AU - Cauley, J. A.

AU - Stone, K. L.

AU - Lui, Li Yung

AU - Ensrud, K. E.

AU - Hillier, T. A.

AU - Hochberg, M. C.

AU - Morin, P.

AU - Peltz, G.

AU - Greene, D.

AU - Cummings, S. R.

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