Measurement of cortical porosity of the proximal femur improves identification of women with nonvertebral fragility fractures

Abstract

We tested whether cortical porosity of the proximal femur measured using StrAx1.0 software provides additional information to areal bone mineral density (aBMD) or Fracture Risk Assessment Tool (FRAX) in differentiating women with and without fracture. Porosity was associated with fracture independent of aBMD and FRAX and identified additional women with fractures than by osteoporosis or FRAX thresholds.

Introduction: Neither aBMD nor the FRAX captures cortical porosity, a major determinant of bone strength. We therefore tested whether combining porosity with aBMD or FRAX improves identification of women with fractures.

Methods: We quantified femoral neck (FN) aBMD using dual-energy X-ray absorptiometry, FRAX score, and femoral subtrochanteric cortical porosity using StrAx1.0 software in 211 postmenopausal women aged 54-94 years with nonvertebral fractures and 232 controls in Tromsø, Norway. Odds ratios (ORs) were calculated using logistic regression analysis.

Results: Women with fractures had lower FN aBMD, higher FRAX score, and higher cortical porosity than controls (all p < 0.001). Each standard deviation higher porosity was associated with fracture independent of FN aBMD (OR 1.39; 95% confidence interval 1.11-1.74) and FRAX score (OR 1.58; 1.27-1.97) in all women combined. Porosity was also associated with fracture independent of FRAX score in subgroups with normal FN aBMD (OR 1.88; 1.21-2.94), osteopenia (OR 1.40; 1.06-1.85), but not significantly in those with osteoporosis (OR 1.48; 0.68-3.23). Of the 211 fracture cases, only 18 women (9%) were identified using FN aBMD T-score < -2.5, 45 women (21%) using FRAX threshold >20%, whereas porosity >80th percentile identified 61 women (29%). Porosity identified 26% additional women with fractures than identified by the osteoporosis threshold and 21% additional women with fractures than by this FRAX threshold.

Conclusions: Cortical porosity is a risk factor for fracture independent of aBMD and FRAX and improves identification of women with fracture.

Fig. 1

a Segmented computed tomography image obtained at the femoral subtrochanter using non-threshold-based image analysis, showing the total cortical area (the area used for the cortical porosity measurements); consisting of the three cortical compartments: compact appearing cortex (green), the outer (white), and inner (red) transitional zones, and trabecular bone area (yellow). b Top left panel shows entire cross section in a 63-year-old woman (subtrochanteric region) acquired using scanning electron microscopy. Bottom Left panel shows the same cross section downsize to simulate a resolution of 740 microns. Top middle panel is magnified regions of interest (ROI) at 12.5 micron resolution pores are clearly visible. Bottom middle panel shows the same ROI but downsized to simulate a resolution of 740 microns. Pores are no longer visible, at least not as empty pixels. Right panels pores which are clearly visible have been color-coded green (top panel). Following the downsizing of the image to simulate a resolution of 740 microns (bottom panel), the presence of porosity in the image signaled by the green color is clearly visible although it does not appear as empty pixels

Fig. 2

To measure porosity, two referent attenuation values are required P: the background (muscle, water etc.) and B: the fully mineralized bone matrix (1200 mg HA/cm³). The proportion of the voxel volume occupied by mineralized bone matrix is its level of fullness (LOF) and is estimated as (LOF) % = (A_i-P)/(B-P), where A_i is the attenuation of voxel i. From LOF, the void volume of each voxel or level of emptiness (porosity) = 100–LOF (%)

Fig. 3

Left panels the correlation between CT and gold standard (HR-pQCT) measurements of porosity of a the compact appearing cortex, b outer and c inner transitional zones, and d the total cortex at the femoral subtrochanter (all p < 0.05). Right panel Bland-Altman plots of the error (difference between measurements by CT and HR-pQCT scanning) ranged from 0 to 10 %, and agreement between both measurements exceeded 90 %

Fig. 4

a Odds ratio (OR) and 95 % confidence interval (CI) for nonvertebral fracture per each standard deviation (SD) lower in femoral neck (FN) areal bone mineral density (aBMD), each SD higher in fracture risk assessment tool (FRAX) score with BMD, each SD higher in FRAX score without BMD, each SD higher in cortical porosity, in all women. b OR (95 % CI) for nonvertebral fracture per each SD higher cortical porosity in women with normal femoral neck areal bone mineral density (FN aBMD, n = 159, 47 with fracture), osteopenia (n = 255, 146 with fracture) and osteoporosis (n = 29, 18 with fracture)

Fig. 5

Venn diagrams illustrate the number and proportion of women identified using threshold for osteoporosis (femoral neck areal bone mineral density (BMD) T-score < −2.5), fracture risk assessment tool (FRAX) score with-BMD >20 %, and cortical porosity >80th percentile, a in 211 women with fracture and b in 232 controls