Don't Forget the Bones: Incidence and Risk Factors of Metabolic Bone Disease in a Cohort of Preterm Infants

Int J Mol Sci. 2022 Sep 14;23(18):10666. doi: 10.3390/ijms231810666.


Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16−23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40−60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.

Keywords: bone disease; nutrition; prematurity.

MeSH terms

  • Alkaline Phosphatase
  • Birth Weight
  • Bone Diseases, Metabolic* / epidemiology
  • Bone Diseases, Metabolic* / etiology
  • Bone Diseases, Metabolic* / prevention & control
  • Calcium
  • Enterocolitis, Necrotizing*
  • Female
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Infant, Very Low Birth Weight
  • Male
  • Phosphorus
  • Pregnancy
  • Premature Birth*
  • Risk Factors


  • Phosphorus
  • Alkaline Phosphatase
  • Calcium

Grants and funding

This study was partially funded by Italian Ministry of Health- Current Research IRCCS 2022.