Bone turnover markers in pediatric alkaptonuria: a case-control study

Alkaptonuria (AKU) is a rare inherited metabolic disorder characterized by progressive connective tissue damage and ochronosis. Although skeletal involvement is well documented in adults with AKU, data on bone metabolism during childhood are limited. This study evaluated bone turnover markers and mineral metabolism parameters in children with AKU.

This cross-sectional case-control study included 16 pediatric patients with AKU and 27 healthy controls. Anthropometric measurements, serum calcium, phosphorus, alkaline phosphatase (ALP), parathyroid hormone, 25-hydroxyvitamin D, osteocalcin, β-C-terminal telopeptide of type I collagen (β-CTX), and urinary homogentisic acid (HGA)/creatinine ratio were assessed. Correlation analyses were performed between bone turnover markers, biochemical parameters, and urinary HGA levels.

Serum calcium concentrations were slightly lower in the AKU group than in controls (p=0.048), although values remained within the reference range in both groups. No significant differences were observed in anthropometric measurements, other mineral metabolism parameters, or bone turnover markers. Urinary HGA levels were not correlated with bone turnover markers. However, the urinary HGA to creatinine ratio showed a moderate negative correlation with body mass index (r=-0.61, p=0.02) and waist circumference (r=-0.58, p=0.02). In healthy controls, osteocalcin and β-CTX correlated positively with ALP and serum phosphorus, whereas these associations were absent in the AKU group.

Our findings suggest that circulating biochemical markers of bone remodeling are preserved in children with AKU. Nevertheless, these results do not exclude early skeletal involvement and support the need for longitudinal studies incorporating additional biomarkers and imaging modalities to better characterize bone health in children with AKU.