Structural patterns of the proximal femur in relation to age and hip fracture risk in women

Julio Carballido-Gamio, Roy Harnish, Isra Saeed, Timothy Streeper, Sigurdur Sigurdsson, Shreyasee Amin, Elizabeth J. Atkinson, Terry M. Therneau, Kristin Siggeirsdottir, Xiaoguang Cheng, L. Joseph Melton, Joyce H. Keyak, Vilmundur Gudnason, Sundeep Khosla, Tamara B. Harris, Thomas F. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97. years) was included in this study, along with a cohort of 222 older women (mean age 79. ±. 7. years) with (n. =74) and without (n. =148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Student's t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction.

Original languageEnglish
Pages (from-to)290-299
Number of pages10
Issue number1
Publication statusPublished - Nov 2013

Bibliographical note

Funding Information:
This study was supported by NIH/NIA R01AG028832 , NIH/NIAMS R01AR46197 , NIH/NIA Professional Services Contract HHSN311200900345P , NIH/NIAMS R01AR027065 , and NIH/NIA R01AG034676 and UL1 TR000135 (Center for Translational Science Activities). The Age, Gene/Environment Susceptibility Reykjavik study is funded by NIH contract N01-AG-12100 , the NIA Intramural Research Program , Hjartavernd (the Icelandic Heart Association) , and the Althingi (the Icelandic Parliament) .

Other keywords

  • Age
  • Fracture
  • Osteoporosis
  • Proximal femur
  • Statistical parametric mapping
  • Tensor-based morphometry (TBM)


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