Bone Disease of Prematurity: Calcium and Phosphorus as Urinary Biomarkers

  • Eveline StaubEmail author
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)


Urinary calcium and phosphorus have been used for the past decades as biomarkers for osteopenia of prematurity. As opposed to the actual diagnosis of decreased bone mineral content, studies have mainly focused on detecting the early phase of mineral deficiency, where bone demineralization might not yet be manifest in radiological images or, worse and as a late complication, by pathological bone fractures. Two methods of urinary mineral markers are used for this purpose: pure urine concentration of calcium and phosphorus or urine calcium/creatinine and phosphorus/creatinine ratios. Urinary calcium and phosphorus concentrations in spot urine samples have been used to guide individualized supplementation over and above the standardized fortified preterm nutrition to achieve bone mineral accretion rates similar to in utero conditions. The idea behind this concept, referred to as slight surplus supply, is that the simultaneous low-level excretion of calcium and phosphorus provides sufficient supply to guarantee adequate bone mineralization, independent of age, weight, and urine volume. Potential pitfalls include the immaturity of the kidneys in preterm infants as well as drugs and kidney diseases, both of which can alter the pattern of mineral excretion without accurately reflecting serum levels. With the other method of urinary mineral assessment, calcium/creatinine and phosphorus/creatinine ratios take into account volume-induced concentration changes. The measurement of excretion of any urine metabolite expressed as ratios over creatinine is standard practice in adult and pediatric nephrology. However, the creatinine excretion in preterm infants does not necessarily only express urine concentration but is possibly dependent on gestational and postnatal age, type of nutrition and renal function. The establishment of reference ranges for calcium/creatinine and phosphorus/creatinine ratios in preterm infants has been attempted but is subject to local nutritional practices and has not been tested against bone mineral content or in the context of individualized mineral supplementation. The existing literature does not answer the question of the superiority of either of the two methods in detecting osteopenia of prematurity. For guidance in individualized calcium and phosphorus supplementation, the concept of slight surplus supply has been shown to work in improving bone mineral accretion (despite methodological shortcomings), while the application of the mineral/creatinine ratios for this purpose is still lacking.


Osteopenia Rickets Metabolic bone disease Bone metabolism Nutrition Supplementation Calcium Phosphorus Mineral Premature Spot urine Excretion 

List of Abbreviations


Alkaline phosphatase






Dual energy X-ray absorptiometry


Double photon absorptiometry


Low birth weight




Single photon absorptiometry


Very low birth weight


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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Division of NeonatologyUniversity of Basel Children’s Hospital UKBBBaselSwitzerland

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