Increased cortical porosity and reduced cortical thickness of the proximal femur are associated with nonvertebral fracture independent of Fracture Risk Assessment Tool and Garvan estimates in postmenopausal women

Abstract

The Fracture Risk Assessment Tool (FRAX) and Garvan Calculator have improved the individual prediction of fracture risk. However, additional bone measurements that might enhance the predictive ability of these tools are the subject of research. There is increasing interest in cortical parameters, especially cortical porosity. Neither FRAX nor Garvan include measurements of cortical architecture, important for bone strength, and providing independent information beyond the conventional approaches. We tested the hypothesis that cortical parameters are associated with fracture risk, independent of FRAX and Garvan estimates. This nested case-control study included 211 postmenopausal women aged 54–94 years with nonvertebral fractures, and 232 controls from the Tromsø Study in Norway. We assessed FRAX and Garvan 10-year risk estimates for fragility fracture, and quantified femoral subtrochanteric cortical porosity, thickness, and area from computed tomography images using StrAx1.0 software. Per standard deviation higher cortical porosity, thinner cortices, and smaller cortical area, the odds ratio (95% confidence interval) for fracture was 1.71 (1.38–2.11), 1.79 (1.44–2.23), and 1.52 (1.19–1.95), respectively. Cortical porosity and thickness, but not area, remained associated with fracture when adjusted for FRAX and Garvan estimates. Adding cortical porosity and thickness to FRAX or Garvan resulted in greater area under the receiver operating characteristic curves. When using cortical porosity (>80th percentile) or cortical thickness (<20th percentile) combined with FRAX (threshold >20%), 45.5% and 42.7% of fracture cases were identified, respectively. Using the same cutoffs for cortical porosity or thickness combined with Garvan (threshold >25%), 51.2% and 48.3% were identified, respectively. Specificity for all combinations ranged from 81.0–83.6%. Measurement of cortical porosity or thickness identified 20.4% and 17.5% additional fracture cases that, were unidentified using FRAX alone, and 16.6% and 13.7% fracture cases unidentified using Garvan alone. In conclusion, cortical parameters may help to improve identification of women at risk for fracture.

Women with fracture, unidentified by FRAX, but identified by cortical porosity, have a set of characteristics that contribute to their increased fracture risk beyond high FRAX score and high cortical porosity

“…In another study using HR-pQCT and StrAx software, cortical porosity of the inner transitional zone at the ultra-distal radius was associated with incident fracture in postmenopausal women independent of femoral neck (FN) aBMD and FRAX score, but only marginally after adjustment for ultra-distal radius aBMD [19]. Our research group has previously reported that increased cortical porosity at the proximal femur was associated with fracture independent of FN aBMD and FRAX [15,20].…”

“…Using a cortical porosity threshold >80 th percentile identified 20% additional fracture cases who were unidentified by FRAX, and improved the net reclassification of fracture cases [20]. This suggests that a measurement of cortical porosity captures other important skeletal properties not captured by the FRAX score.…”

“…In 2011 we designed a nested case-control study and identified 1250 women from the x-ray-based fracture registry that suffered at least one fracture of the hip, wrist, or proximal humerus after the age of 50 years [15,20,[23][24][25]. We invited all 760 women who were still alive and living in Tromsø.…”

“…Since metal on one hip can create noise in the CT images on both sides, many women with a hip fracture could not be included unless they had the metal removed. After screening, 264 fracture cases were included in the study [15,20,23,24]. Age-matched, fracture-free women, who were within the same 5-year age groups, were randomly selected from the Tromsø 4 participants, and 1186 were invited.…”

“…We entered the data collected at enrollment into the online country-specific FRAX algorithm for Norway to calculate the individual 10-year probability of a major osteoporotic fracture (http://www.shef.ac.uk/FRAX/). An age of 90 years was entered into the calculation tool in women older than 90 years of age, and we included FN aBMD in the calculation of FRAX score [20]. The index fractures used as inclusion criteria for this study were not included as a "previous" fracture in the calculation of the FRAX score, because the aim was to assess the 10-year probability of fracture before the event, not the probability of fracture after this event [14,15].…”