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Biochemical markers for metabolic bone disease in preterm infants: insights from a structured Bone Health Programme
Saif Alsaif1,2,3, Talal Aljarbou1,3, Mohanned Alrahili1,3
1Neonatal Intensive Care Department, King Abdulaziz Medical City in Riyadh, Riyadh, Saudi Arabia.
Insights
Peak parathyroid hormone (PTH) is the most accurate biomarker for identifying metabolic bone disease in preterm infants, outperforming alkaline phosphatase (ALP) and phosphate. Routine PTH screening can improve early detection of osteopenia and reduce fractures.
Area of Science:
- Neonatal Medicine
- Pediatric Endocrinology
- Biochemistry
Background:
- Metabolic bone disease is a significant concern in preterm infants.
- Accurate prediction and early diagnosis are crucial for effective management and prevention of complications like fractures.
Purpose of the Study:
- To identify clinical and biochemical predictors of metabolic bone disease in preterm infants.
- To assess the diagnostic performance of serum biomarkers, including parathyroid hormone (PTH), alkaline phosphatase (ALP), phosphate, and 25-OH vitamin D, for radiographic osteopenia.
Main Methods:
- Retrospective cohort study of 484 preterm infants (<28 weeks gestation or <1000g birth weight).
- Radiographic osteopenia assessed via standardized babygrams; biochemical markers measured.
- Receiver operating characteristic (ROC) analysis used to determine the diagnostic accuracy of biomarkers.
Main Results:
- Radiographic osteopenia observed in 7.2% of infants, with 1.9% experiencing fractures.
- Elevated peak PTH levels were significantly associated with osteopenia (p<0.001).
- Peak PTH demonstrated the highest diagnostic accuracy (AUC 0.821) for radiographic osteopenia, surpassing ALP and phosphate levels.
Conclusions:
- Peak PTH is the most accurate serum biomarker for diagnosing radiographic osteopenia in preterm infants.
- Integrating PTH into routine screening protocols, alongside ALP and phosphate, can enhance early identification of metabolic bone disease.
- Improved early detection may lead to better mineral optimization, reduced fracture rates, and streamlined follow-up care for vulnerable preterm infants.
Objective:
To evaluate clinical and biochemical predictors of metabolic bone disease in preterm infants and determine the diagnostic performance of serum biomarkers for radiographic osteopenia.
Design:
Retrospective cohort study.
Setting:
Level III tertiary neonatal intensive care unit, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Patients:
484 infants born at <28 weeks' gestation or birth weight <1000 g enrolled in a structured Bone Health Programme (2017-2024); infants who died before 4 weeks or had skeletal dysplasia/genetic bone disease were excluded.
Main Outcome Measures:
Radiographic osteopenia on standardised anteroposterior babygrams. Biomarkers included parathyroid hormone (PTH), alkaline phosphatase (ALP), phosphate and 25-OH vitamin D. A paediatric radiologist, blinded to biochemistry, classified images using predefined criteria. Predictive accuracy was assessed with receiver operating characteristic (ROC) analysis; non-parametric tests were used for group comparisons.
Results:
Biochemical abnormalities were common: hypophosphataemia <1.8 mmol/L in 38% and <1.6 mmol/L in 25%; elevated PTH >10 pmol/L in 77% and >18 pmol/L in 43%; ALP >500 IU/L in 21%; vitamin D <50 nmol/L in 41%. Radiographic osteopenia occurred in 35/484 (7.2%), including 9 fractures (1.9% of the cohort; 25.7% of osteopenia). Compared with infants without osteopenia, affected infants had higher peak PTH (33.2 vs 19.6 pmol/L, p<0.001), screening PTH (21.4 vs 14.2 pmol/L, p=0.002) and peak ALP (558 vs 427 IU/L, p=0.006). On ROC analysis, peak PTH showed the best discrimination for radiographic osteopenia (area under the curve, AUC 0.821, 95% CI 0.754 to 0.889; optimal cut-off >28.7 pmol/L), followed by screening PTH (AUC 0.761, 95% CI 0.676 to 0.845; cut-off >17.6 pmol/L) and peak ALP (AUC 0.657, 95% CI 0.563 to 0.750; cut-off >525 IU/L).
Conclusions:
In this large single-centre cohort, peak PTH was the most accurate biochemical marker for radiographic osteopenia, outperforming ALP and phosphate. Incorporating PTH into routine screening, alongside ALP and phosphate, may improve early identification and targeted mineral optimisation, potentially reducing fractures and streamlining follow-up.
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