Adding Marrow Adiposity and Cortical Porosity to Femoral Neck Areal Bone Mineral Density Improves the Discrimination of Women with Nonvertebral Fractures from Controls.

Abstract

Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly due to diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration will be associated with an increased marrow adiposity, and each of these traits will be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the distal tibia and distal radius in 77 women aged 40-70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR-pQCT images was validated using direct histologic measurement as gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each standard deviation (SD) higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, 0.60 SD fewer, 0.24 SD thinner and 0.72 SD more separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (95% confidence interval) for fracture per SD higher marrow adiposity and cortical porosity were 3.39 (2.14-5.38) and 1.79 (1.14-2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (AUC 0.778 vs. 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 vs. 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve identification of women at risk for fractures requires validation in prospective studies. This article is protected by copyright. All rights reserved.