Genetic determinant of trabecular bone score (TBS) and bone mineral density: A bivariate analysis

Abstract

This study sought to estimate the extent of genetic influence on the variation in trabecular bone score (TBS). We found that genetic factors accounted for ~45% of variance in TBS, and that the co-variation between TBS and bone density is partially determined by genetic factors.

Introduction: Trabecular bone score has emerged as an important predictor of fragility fracture, but factors underlying the individual differences in TBS have not been explored. In this study, we sought to determine the genetic contribution to the variation of TBS in the general population.

Methods: The study included 556 women and 189 men from 265 families. The individuals aged 53years (SD 11). We measured lumbar spine bone mineral density (BMD; Hologic Horizon) and then derived the TBS from the same Hologic scan where BMD was derived. A biometric model was applied to the data to partition the variance of TBS into two components: one due to additive genetic factors, and one due to environmental factors. The index of heritability was estimated as the ratio of genetic variance to total variance of a trait. Bivariate genetic analysis was conducted to estimate the genetic correlation between TBS and BMD measurements.

Results: TBS was strongly correlated with lumbar spine BMD (r=0.73; P<0.001). On average TBS in men was higher than women, after adjusting age and height which are significantly associated with both TBS and lumbar spine BMD. The age and height adjusted index of heritability of TBS was 0.46 (95% CI, 0.39-0.54), which was not much different from that of LSBMD (0.44; 95% CI, 0.31-0.55). Moreover, the genetic correlation between TBS and LSBMD was 0.35 (95% CI, 0.21-0.46), between TBS and femoral neck BMD was 0.21 (95% CI, 0.10-0.33).

Conclusions: Approximately 45% of the variance in TBS is under genetic influence, and this effect magnitude is similar to that of lumbar spine BMD. This finding provides a scientific justification for the search for specific genetic variants that may be associated with TBS and fracture risk.

Keywords: Genetic factors; Index of heritability; Osteoporosis; Trabecular bone score.