Fracture history of healthy premenopausal women is associated with a reduction of cortical microstructural components at the distal radius

Objectives The objective of this study is to determine in healthy premenopausal women with a history of fracture which bone structural components of the distal radius are the most closely associated with a risk of fracture. Methods and participants The method was as follows: measurement of radial areal bone mineral density (aBMD) by DXA, microstructural components by high-resolution quantitative peripheral computerized tomography (HR-pQCT) and strength variables by micro Finite Element Analysis (µFEA) in 196 healthy premenopausal women aged 45.9 ± 3.7 (± SD) years with (FX, n = 96) and without (NO-FX, n = 100) a history of fracture. We evaluated differences in T-scores between FX and NO-FX and risk of fracture by Odds ratios (OR with 95% confidence intervals, CI) per one SD decrease, using logistic regression analysis after adjustment for age, height, weight, menarcheal age, calcium and protein intakes, and physical activity. Results In the whole group the mean radial metaphysis aBMD T-score was not significantly different from zero. In the FX as compared to the NO-FX group, the differences in T-scores were as follows: for radial metaphysis: aBMD, - 0.24 (P = 0.005); for distal radius microstructure components: cortical volumetric BMD, - 0.38 (P = 0.0009); cortical thickness, - 0.37 (P = 0.0001); cross-sectional area (CSA), + 0.24 (P = 0.034); and endosteal perimeter, + 0.28 (P = 0.032); and for strength estimates: stiffness, - 0.15 (P = 0.030); failure load, - 0.14 (P = 0.044); and apparent modulus, - 0.28 (P = 0.006). T-scores of trabecular volumetric BMD and thickness did not significantly differ between the FX and the NO-FX group. Accordingly, the risk of fracture (OR, 95% CI) for 1 SD decrease in radius bone parameters was as follows: radial metaphysis aBMD: 1.70 (1.18–2.44), P = 0.004; cortical volumetric BMD: 1.86 (1.28–2.71), P = 0.001; and cortical thickness: 2.36 (1.53–3.63), P = 0.0001. The corresponding fracture risk for the strength estimates was as follows: stiffness: 1.66 (1.06–2.61), P = 0.028; failure load: 1.59 (1.02–2.47), P = 0.041; and apparent modulus: 1.76 (1.17–2.64), P = 0.006. Conclusions In healthy premenopausal women, a history of fracture is associated with reduced T-scores in the distal radius, with the cortical components showing the greatest deficit. A reduction of one SD in cortical thickness is associated with a nearly three-fold increased risk of fracture. This finding strengthens the notion that, in healthy women, a certain degree of bone structural fragility contributes to fractures before the menopause and therefore should be taken into consideration in the individual prevention strategy of postmenopausal osteoporosis. Keywords : Healthy premenopausal women; Fracture risk; Areal and volumetric BMD; Microstructure; HR-pQCT; Bone strength