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Body Composition and Bone Mineral Density in Children with Premature Adrenarche and the Association of LRP5 Gene Polymorphisms with Bone Mineral Density

Departments of Pediatrics (P.U., J.J., R.V.) and Clinical Physiology and Nuclear Medicine (E.V.), University of Kuopio and Kuopio University Hospital, FI-70211 Kuopio, Finland; Department of Medical Genetics (A.S.), University of Helsinki, and Folkhälsan Institute of Genetics (A.S., O.M.), Biomedicum Helsinki, FI-00290 Helsinki, Finland; and Metabolic Bone Clinic (O.M.), Hospital for Children and Adolescents, Helsinki University Hospital, FI-00029 Helsinki, Finland

Address all correspondence and requests for reprints to: Pauliina Utriainen, Department of Pediatrics, Kuopio University and University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland. E-mail: pauliina.utriainen{at}uku.fi.

Context: Precocious increase in adrenal androgen production is the hallmark of premature adrenarche (PA). Adrenal androgens have anabolic properties.

Objective: The objective of the study was to test whether body composition and bone mineral density (BMD) are altered in PA and study whether genetic variation in low-density lipoprotein receptor-related protein 5 (LRP5) affects BMD in PA.

Design: This was a cross-sectional study.

Setting: The study was conducted at a university hospital.

Subjects and Measures: The study included 126 prepubertal children (64 with PA, 10 boys; 62 non-PA controls, 10 boys). Femoral neck and lumbar spine areal and calculated volumetric BMD (dual energy X-ray absorptiometry), body composition (bioimpedance), serum 25-hydroxyvitamin D, and markers of bone turnover and calcium homeostasis were compared between the PA and control groups. Single-nucleotide polymorphisms of LRP5 were determined and associated with BMD.

Results: Children with PA had higher femoral neck and lumbar spine BMD_areal than the controls (Z-score 0.56 vs. –0.09, P < 0.001, and 0.20 vs. –0.31, P = 0.009, respectively). However, the mean BMDs did not differ significantly between the groups when adjusted for height or bone size. BMD_areal correlated strongly with height SD score in both groups. Among the PA children, LRP5 single-nucleotide polymorphism E644E minor variant was associated with lower and F549F minor variant with higher BMD. Total body fat mass, fat percent, serum PTH, and alkaline phosphatase concentrations were higher and 25-hydroxyvitamin D lower in the PA group.

Conclusions: Prepubertal children with PA had higher BMD_areal compared with healthy controls. This was mainly explained by their increased height. LRP5 polymorphisms may contribute to bone mass accrual in prepubertal PA children.