Early elevated alkaline phosphatase as a surrogate biomarker of ongoing metabolic bone disease of prematurity

Very low birth weight (VLBW) neonates present a high risk of metabolic bone disease (MBD). Our main objective was to determine the easiest way to make an early diagnosis of this disease by identifying surrogate biomarkers before any radiological signs occurred. We conducted in our NICU a 6-month observational prospective study, with inclusion of all singleton VLBW neonates. We collected clinical and biological data, and nutritional intakes during hospitalization. We defined biological MBD (bMBD) as alkaline phosphatase (ALP) levels superior to 600 UI/L at day of life 30 (DOL30) and performed a case-control analysis. Nine out of 30 patients (30%) exhibited bMBD. All have extremely low birth weight and were significantly younger in gestational age (GA) and smaller at birth. There was no statistically significant difference in nutritional intake between bMBD and control groups. In the bMBD group, phosphatemia was lower since DOL3. ALP was already significantly higher at DOL15, and way beyond normal range.

Conclusions: Our results showed that even the strict respect of nutritional guidelines cannot completely prevent bMBD in high-risk patients and suggest that an early screening from DOL15, with ALP levels greater than 500 UI/L, could be sufficient for detection of upcoming MBD.

What is known: • Metabolic bone disease of prematurity (MBD) definition is not consensual, but biological changes appear earlier than radiological signs of rickets. • MBD management relies on biological evidence. Treatment is based on phosphate and/or calcium and calcitriol supplementation.

What is new: • Studying phosphocalcic biological assessment in very low birth weight neonates, we showed respect of nutritional guidelines could not protect from biological MBD. • Increase in alkaline phosphatase (ALP), about 500 UI/l at day of life 15, could be a biomarker of MBD with no need of X-ray evaluation and sufficient to begin a treatment to prevent osteopenia.