Cortical and trabecular bone microarchitecture predicts incident fracture independently of DXA bone mineral density and FRAX in older women and men: The Bone Microarchitecture International Consortium (BoMIC)

Background: Although dual-energy x-ray absorptiometry (DXA) assessed areal bone density (aBMD) is the clinical standard for determining fracture risk, the majority of older adults who sustain a fracture do not have osteoporosis (T-score < −2.5). Importantly, bone fragility results not only from low BMD, but also from deterioration in bone structure. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) data from eight cohorts to evaluate whether HR-pQCT indices were associated with fracture risk independently of femoral neck (FN) aBMD and FRAX (Fracture Risk Assessment Tool) score. Methods: Participants included 7,254 individuals (66% women) from cohorts in the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), proportional hazards ratios (HRs) for the association between bone parameters (per standard deviation, SD, deficit) and incident fracture, adjusting for age, sex, height, weight and cohort. Findings: Mean baseline age was 69 (±9) years (range, 40 to 96). Cumulative incidence of fracture was 11% (n=765) over a mean follow-up time of 4.6 (± 2.4) years. The majority of participants (92%) had a femoral neck T-score >−2.5, and thus did not meet diagnostic criteria for osteoporosis. Failure load was the bone measure most strongly associated with risk of fracture: tibia HR=2.40 (1.98-2.91), radius HR=2.13 (1.77-2.56), per SD decrease in failure load. HRs for other bone indices ranged from HR=1.12 (1.03-1.23) per SD increase in tibia cortical porosity to HR=1.58 (1.45-1.72) per SD decrease in radius trabecular volumetric bone density (vBMD). After further adjustment for FN aBMD or FRAX, HRs were attenuated, but most bone parameters remained significantly associated with fracture. Cortical density, trabecular number, and trabecular thickness at the distal radius were the best set of predictors of fracture; while the same indices plus cortical area were identified for the tibia. These HR-pQCT indices and failure load improved prediction of fracture, beyond FN aBMD alone or FRAX. Interpretation: Results from this large international cohort of women and men confirm prior studies showing that deficits in trabecular and cortical bone density and structure contribute to fracture risk independently of aBMD and FRAX. Measurements of cortical and trabecular bone density and morphology at the peripheral skeleton may improve identification of those at highest risk for fracture.