Bone strength estimated by micro finite element analysis (μFEA) is heritable and shares genetic predisposition with areal BMD: The Framingham Study

摘要

Genetic factors contribute to the risk of bone fractures, partly due to 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 BMD (aBMD).Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n=1,087, mean age 72 ys old; 57% women). Radial and tibial failure load in compression were estimated by μFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by 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 (ρP =0.826, ρG =0.954, respectively), while environmental correlations were lower (ρE=0.696), all highly significant (p<0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρP = 0.577, ρG = 0.703, both p<0.001;ρE= 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.