Bone Strength Estimated by Micro-Finite Element Analysis (µFEA) Is Heritable and Shares Genetic Predisposition With Areal BMD: The Framingham Study

Genetic factors contribute to the risk of bone fractures, partly because of effects on bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) estimates bone strength using micro-finite element analysis (µFEA). The goal of this study was to investigate if the bone failure load estimated by HR-pQCT-based µFEA is heritable and to what extent it shares genetic regulation with areal bone mineral density (aBMD). Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n = 1087, mean age 72 years; 57% women). Radial and tibial failure load in compression were estimated by µFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by dual-energy X-ray absorptiometry (DXA). Heritability (h²) of failure load and aBMD and genetic correlations between them was estimated adjusting for covariates (age and sex). Failure load values at the non-weight-bearing ultradistal radius and at the weight-bearing ultradistal tibia were highly correlated (r = 0.906; p < 0.001). Estimates of h² adjusted for covariates were 0.522 for the radius and 0.497 for the tibia. Additional adjustment for height did not impact on the h² results, but adjustment for aBMD at the UD and FN somewhat decreased h² point estimates: 0.222 and 0.380 for radius and tibia, respectively. In bivariate analysis, there was a high phenotypic and genetic correlation between covariate-adjusted failure load at the radius and UD aBMD (ρ_P = 0.826, ρ_G = 0.954, respectively), whereas environmental correlations were lower (ρ_E = 0.696), all highly significant (p < 0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρ_P = 0.577, ρ_G = 0.703, both p < 0.001; ρ_E= 0.432, p < 0.05). These data from adult members of families from a population-based cohort suggest that bone strength of distal extremities estimated by micro-finite element analysis is heritable and shares some genetic composition with areal BMD, regardless of the skeletal site.