Screening for Metabolic Bone Disease of prematurity

Semin Fetal Neonatal Med. 2020 Feb;25(1):101086. doi: 10.1016/j.siny.2020.101086. Epub 2020 Jan 16.


Metabolic bone disease (MBD) of prematurity remains a significant comorbid condition in preterm, low birth weight infants. As the majority of in utero calcium (Ca) and phosphorus (Phos) accretion occurs during the third trimester, many of these children have inadequate mineral stores and are at risk for deficiencies of Ca and Phos. While fortification of formula has allowed for increased mineral delivery to premature infants, intestinal immaturity prevents optimal absorption. This is compounded by immobilization, delayed establishment of enteral feeds, long term parenteral nutrition and medications that may alter mineral levels. Over time, biochemical changes occur and accompany MBD, with poor bone mineralization during this period increasing the risk for complications such as osteopenia, rickets and fractures. Screening is largely based on risk factors, but despite the 2013 AAP Consensus Statement, there remains significant variation in screening practices across institutions. A combination of laboratory and radiologic testing is often used to diagnose and manage MBD of prematurity, but there exists a lack of consensus on which screening tests and thresholds to use. This is in part related to a lack of normative data and clinical trials for preterm infants, and a result, a lack of evidence-based guidelines on the diagnosis and timing of potential treatment. Biochemical markers, such as serum Phos, alkaline phosphatase (ALP) and parathyroid hormone (PTH), have shown some benefit in the diagnosis of MBD in some studies, but have not always been reproducible. Radiographs may identify different degrees of skeletal changes, but these changes may not be detected until later in MBD development. Other modalities, such as DXA and ultrasound, have also been used, but these may be limited by lack of standards in preterm infants or lack of availability in some centers. Further research, more specifically clinical trials, are needed to determine which combination of tests can detect MBD at its earliest, in order to promote early treatment and prevent short- and long-term complications of MBD.

Keywords: Alkaline phosphatase (ALP); Calcium (Ca); Metabolic bone disease (MBD) of prematurity; Osteopenia of prematurity; Phosphorus (Phos); Rickets; Tubular reabsorption of phosphorus (TRP).

Publication types

  • Review

MeSH terms

  • Bone Diseases, Metabolic / diagnosis*
  • Bone Diseases, Metabolic / metabolism
  • Calcium / metabolism
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Neonatal Screening*
  • Phosphorus / metabolism


  • Phosphorus
  • Calcium