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LRP5 polymorphisms may be associated with increased bone mass in prepubertal children with premature adrenarche

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Prepubertal children with premature adrenarche had higher bone mineral density when compared with healthy children in a new cross-sectional study. However, bone size-adjusted BMD or height-adjusted BMD was not significantly different between the two groups.

Researchers in Finland assessed whether BMD and body composition were changed in 126 prepubertal children with (n=64; 10 boys) and without (n=62; 10 boys) premature adrenarche, and further assessed whether genetic variation in LDL receptor-related protein 5 affected BMD in premature adrenarche.

Children were divided into three groups on the basis of physical activity:

• Occasional or no physical activity in addition to school-based physical education.
• Regular after-school physical activity.
• Participation in competitive sports or exercising daily.

Premature adrenarche vs. healthy controls

When compared with the control group, children with premature adrenarche had higher femoral neck and lumbar spine BMD (z-score: 0.56 vs. –0.09; P<.001 and 0.20 vs. –0.31; P=.009). After adjustment for height or bone size, mean BMD was not significantly different between the groups.

Femoral neck and BMD were significantly associated with height SD score (R=0.43-0.45, R=0.62–0.63; P<.001). A moderate association was observed with BMI SDS (R=0.29-0.39; P<.03).

Of the children with premature adrenarche, LRP5 single-nucleotide polymorphism E644E minor variant was associated with lower BMD and F549F minor variant was associated with higher BMD.

Height SD score (P=.002) and physical activity (P=.045) were the only parameters independently associated with lumbar spine BMD in the control group. However, height SDS (P<.001), age (P<.001) and male sex(P=.036) were positively associated with femoral neck BMD.

“Our results indicate that growth in height and bone size, and to a lesser extent body weight, are more important determinants of bone mass accrual than increased circulating adrenal androgen concentrations in prepubertal children,” the researchers concluded. “Genetic variation in LRP5 may slightly contribute to BMD in prepubertal premature adrenarche children.”

Utriainen P. J Clin Endocrinol Metab. 2009;94:4144-4151.