The Clinical and Biochemical Predictors of Bone Mass in Preterm Infants

PLoS One. 2016 Nov 2;11(11):e0165727. doi: 10.1371/journal.pone.0165727. eCollection 2016.


Background: Metabolic bone disease of prematurity still occurs in preterm infants, although a significant improvement in neonatal care has been observed in recent decades. Dual-energy X-ray absorptiometry (DXA) is the precise technique for assessing bone mineral content (BMC) in preterm infants, but is not widely available.

Aim: To investigate the clinical and biochemical parameters, including bone metabolism markers as potential predictors of BMC, in preterm infants up to 3 months corrected age (CA).

Materials and methods: Ca-P homeostasis, iPTH, 25-hydroxyvitamin D, osteocalcin, N-terminal propeptide, cross-linked C-telopeptide and amino-terminal pro C-type natriuretic peptide and the DXA scans were prospectively performed in 184 preterm infants (≤ 34 weeks' gestation) between term age and 3 mo CA. Lower bone mass was defined as BMC below or equal to respective median value for the whole study group, rounded to the nearest whole number.

Results: The appropriate quality DXA scans were available for 160 infants (87%) examined at term and for 130 (71%) tested at 3 mo CA. Higher iPTH level was the only independent predictor of lower BMC at term, whereas lower BMC at 3 mo CA was associated both with lower urinary phosphate excretion and higher serum osteocalcin level. ROC analysis showed that iPTH >43.6 pg/mL provided 40% sensitivity and 88% specificity in identification of preterm infants with lower BMC at term. In turn, urinary phosphate excretion (TRP>97% or UP/Cr ≤0.74 mg/mg) and serum osteocalcin >172 ng/mL provided 40% sensitivity and 93% specificity in identification of infants with decreased BMC at 3 mo CA.

Conclusion: Serum iPTH might to be a simple predictor of reduced BMC in preterm infants at term age, but urinary phosphate excretion and serum osteocalcin might predict reduced BMC at 3 mo CA. These results represent a promising diagnostic tool based on simple, widely available biochemical measurements for bone mass assessment in preterm infants.

MeSH terms

  • Absorptiometry, Photon / methods*
  • Biomarkers / metabolism*
  • Bone Density*
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Male
  • Natriuretic Peptide, C-Type / metabolism
  • Osteocalcin / blood
  • Parathyroid Hormone / blood*
  • Phosphates / urine
  • ROC Curve
  • Sensitivity and Specificity
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism


  • Biomarkers
  • Parathyroid Hormone
  • Phosphates
  • Osteocalcin
  • Natriuretic Peptide, C-Type
  • Vitamin D
  • 25-hydroxyvitamin D

Grants and funding

A statutory grant of the Children’s’ Memorial Health Institute No. 173/2007 (JCK).Prof Anna Dobrzanska is a recipient of a statutory grant of the Children's Memorial Health 23/2004. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.