Heritability of Changes in Bone Size and Bone Mass With Age in Premenopausal White Sisters

Abstract

Femoral neck area expands and BMD decreases in premenopausal women. We used longitudinal DXA measurements on 388 premenopausal white sisters to show significant heritability of the rates of change in femoral neck area, BMC, and BMD. Bone mass and structure are highly heritable. However, genetic effects on age-related changes in bone mass and structure in adults have been much less studied. DXA measurements were made on 388 healthy white premenopausal sisters from 178 families. Rates of change in femoral neck area, BMC, and BMD, as well as body weight, were calculated from two measurements made an average of 5.7 years apart. Mixed models were used to test whether bone changes were related to age or weight change. Variance components models were used to estimate the heritability of the rates of change. A method was proposed to correct for the underestimation of heritabilities caused by measurement errors of the rates of change. Femoral neck area increased with age, whereas BMD decreased. All of the rates of change at the femoral neck were positively correlated with weight change, but the rates of femoral neck changes did not vary with age. Adjusted for weight change, change in femoral neck BMC became negative. Significant heritabilities (0.29-0.36) were detected for changes in femoral neck BMC, BMD, and area adjusted for weight changes. Correction for DXA measurement error in the rate estimates increased the heritability estimates (from 0.29-0.36 range to 0.37-0.64 range). Rates of change are heritable for femoral neck area, BMC, and BMD in premenopausal white women.