Circulating Matrix GLA Protein During Puberty in Healthy and Central Precocious Puberty Children

OBJECTIVE: Matrix Gla-protein (MGP) is involved in the regulation of extracellular matrix mineralisation, including bone formation. The peripubertal years are critical for linear growth and acquisition of bone mass. Emerging evidence suggests that plasma concentrations of dephosphorylated undercarboxylated MGP (dp-ucMGP) may vary across pubertal stages, potentially reflecting its role in bone remodelling. METHODS: This study examines longitudinal changes in circulating plasma dp-ucMGP in two cohorts: 111 healthy Danish children (52% girls) aged 6-15 years from the Copenhagen Puberty Study and 15 female patients with central precocious puberty (CPP) before, during, and after GnRH analogue treatment. RESULTS: Age- and sex-specific reference curves were generated for healthy children and adolescents. Dp-ucMGP increased significantly with age and pubertal progression in both sexes, while it declined from mid-puberty exclusively in boys. In girls only, dp-ucMGP SD-scores were associated with body weight and BMI. In girls with CPP, dp-ucMGP concentrations were lower compared to healthy puberty-matched girls (Tanner B2: p=0.016, Tanner B3: p=0.0072). Initiation of GnRH agonist in CPP resulted in a significant increase in dp-ucMGP (-1.21 SD (baseline) vs 0.30 SD (3 months), p=0.0048) but plateaued after 12 months of treatment and further declined towards baseline at treatment cessation. CONCLUSION: We show that circulating dp-ucMGP concentrations increase with age and pubertal progression in healthy children, are lower in CPP patients, and are suppressed by GnRH agonist. Altogether, our findings support that circulating concentrations of dp-ucMGP reflect its role in bone remodelling and linear growth during puberty.